Biaryl heterocyclic compounds and methods of making and using the same

[0001] This application claims the benefit of and priority to U.S. Patent Application Nos. 60/475,430, filed Jun. 3, 2003; 60/475,453, filed Jun. 3, 2003; 60/490,855, filed Jul. 29, 2003; 60/529,731, filed Dec. 15, 2003; and 60/531,584, filed Dec. 19, 2003, the enclosures of which are incorporated by reference herein.

[0002] The present invention relates generally to the field of anti-infective, anti-proliferative, anti-inflammatory, and prokinetic agents. More particularly, the invention relates to a family of biaryl heterocyclic compounds, comprising both a biaryl moiety and at least one heterocyclic moiety, that are useful as therapeutic agents.

[0003] Since the discovery of penicillin in the 1920s and streptomycin in the 1940s, many new compounds have been discovered or specifically designed for use as antibiotic agents. It was once believed that infectious diseases could be completely controlled or eradicated with the use of such therapeutic agents. However, such beliefs have been shaken by the fact that strains of cells or microorganisms resistant to currently effective therapeutic agents continue to evolve. In fact, virtually every antibiotic agent developed for clinical use has ultimately encountered problems with the emergence of resistant bacteria. For example, resistant strains of Gram-positive bacteria such as methicillin-resistant staphylocci, penicillin-resistant streptococci, and vancomycin-resistant enterococci have developed, which can cause serious and even fatal results for patients infected with such resistant bacteria. Bacteria that are resistant to macrolide antibiotics, i.e., antibiotics based on a 14- to 16-membered lactone ring, have developed. Also, resistant strains of Gram-negative bacteria such as H. influenzae and M. catarrhalis have been identified. See, e.g., F. D. Lowry, “Antimicrobial Resistance: The Example of Staphylococcus aureus,” J Clin. Invest., 2003, 111(9), 1265-1273; and Gold, H. S. and Moellering, R. C., Jr., “Antimicrobial-Drug Resistance,” N. Engl. J Med., 1996, 335, 1445-53.

[0004] The problem of resistance is not limited to the area of anti-infective agents, because resistance has also been encountered with anti-proliferative agents used in cancer chemotherapy. Therefore, there exists a need for new anti-infective and anti-proliferative agents that are both effective against resistant bacteria and resistant strains of cancer cells.

[0005] In the antibiotic area, despite the problem of increasing antibiotic resistance, no new major classes of antibiotics have been developed for clinical use since the approval in the United States in 2000 of the oxazolidinone ring-containing antibiotic, N-[[(5S)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl acetamide, which is known as linezolid and is sold under the tradename Zyvox® (see compound A). See, R. C. Moellering, Jr., “Linezolid: The First Oxazolidinone Antimicrobial,” Annals of Internal Medicine, 2003, 138(2), 135-142.

[0006] Linezolid was approved for use as an anti-bacterial agent active against Gram-positive organisms. Unfortunately, linezolid-resistant strains of organisms are already being reported. See, Tsiodras et al., Lancet, 2001, 358, 207; Gonzales et al., Lancet, 2001, 357, 1179; Zurenko et al., Proceedings Of The 39^th Annual Interscience Conference On Antibacterial Agents And Chemotherapy (ICAAC); San Francisco, Calif., USA, (Sep. 26-29, 1999). Because linezolid is both a clinically effective and commercially significant anti-microbial agent, investigators have been working to develop other effective linezolid derivatives.

[0007] Notwithstanding the foregoing, there is an ongoing need for new anti-infective and anti-proliferative agents. Furthermore, because many anti-infective and anti-proliferative agents have utility as anti-inflammatory agents and prokinetic agents, there is also an ongoing need for new compounds useful as anti-inflammatory and prokinetic agents.

[0008] The invention provides a family of compounds useful as anti-infective agents and/or anti-proliferative agents, for example, chemotherapeutic agents, anti-microbial agents, anti-bacterial agents, anti-fungal agents, anti-parasitic agents, anti-viral agents, anti-inflammatory agents, and/or prokinetic (gastrointestinal modulatory) agents. The compounds have the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein Het-CH₂-R⁴ is selected from the group consisting of:
A and B independently are selected from the group consisting of phenyl, pyridyl, pyrazinyl, pyrimidinyl, and pyridazinyl; M-L is selected from the group consisting of M-X, M-L¹, M-L¹-X, M-X-L², M-L¹-X-L², M-X-L¹-X-L², M-L¹-X-L²-X, M-X-X-, M-L¹-X-X-, M-X-X-L², and M-L¹-X-X-L²; M is an optionally substituted saturated, unsaturated, or aromatic C_3-14 carbocycle, or an optionally substituted saturated, unsaturated, or aromatic 3-14 membered heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur; and the variables L¹, L², M, R¹, R², R³, X, m, and n are selected from the respective groups of chemical moieties or integers later defined in the detailed description.

[0009] Particular embodiments of compounds of the invention include those having the formula:
wherein the variables A, L, M, R¹, R³, and m are selected from the respective groups of chemical moieties or integers later defined in the detailed description.

[0010] In addition, the invention provides methods of synthesizing the foregoing compounds. Following synthesis, an effective amount of one or more of the compounds may be formulated with a pharmaceutically acceptable carrier for administration to a mammal for use as an anti-cancer, anti-microbial, anti-biotic, anti-fungal, anti-parasitic or anti-viral agent, or to treat a proliferative disease, an inflammatory disease or a gastrointestinal motility disorder. The compounds or formulations may be administered, for example, via oral, parenteral, or topical routes, to provide an effective amount of the compound to the mammal.

[0011] The foregoing and other aspects and embodiments of the invention may be more fully understood by reference to the following detailed description and claims.

[0012] The present invention provides a family of compounds that can be used as anti-proliferative agents and/or anti-infective agents. The compounds may be used without limitation, for example, as anti-cancer, anti-microbial, anti-bacterial, anti-fungal, anti-parasitic and/or anti-viral agents. Further, the present invention provides a family of compounds that can be used without limitation as anti-inflammatory agents, for example, for use in treating chronic inflammatory airway diseases, and/or as prokinetic agents, for example, for use in treating gastrointestinal motility disorders such as gastroesophageal reflux disease, gastroparesis (diabetic and post surgical), irritable bowel syndrome, and constipation.

1. Definitions

[0013] The term “substituted,” as used herein, means that any one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. When a substituent is keto (i.e., ═O), then 2 hydrogens on the atom are replaced. Keto substituents are not present on aromatic moieties. Ring double bonds, as used herein, are double bonds that are formed between two adjacent ring atoms (e.g., C═C, C═N, or N═N).

[0014] The present invention is intended to include all isotopes of atoms occurring in the present compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include tritium and deuterium, and isotopes of carbon include C-13 and C-14.

[0015] The compounds described herein may have asymmetric centers. Compounds of the present invention containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. Many geometric isomers of olefins, C═N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms. All chiral, diastereomeric, racemic, and geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomeric form is specifically indicated. All processes used to prepare compounds of the present invention and intermediates made therein are considered to be part of the present invention. All tautomers of shown or described compounds are also considered to be part of the present invention.

[0016] When any variable (e.g., R¹) occurs more than one time in any constituent or formula for a compound, its definition at each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 0-2 R¹ moieties, then the group may optionally be substituted with up to two R¹ moieties and R¹ at each occurrence is selected independently from the definition of R¹. Also, combinations of substituents and/or variables are permissible, but only if such combinations result in stable compounds.

[0017] When a bond to a substituent is shown to cross a bond connecting two atoms in a ring, then such substituent may be bonded to any atom in the ring. When a substituent is listed without indicating the atom via which such substituent is bonded to the rest of the compound of a given formula, then such substituent may be bonded via any atom in such substituent. Combinations of substituents and/or variables are permissible, but only if such combinations result in stable compounds.

[0018] Compounds of the present invention that contain nitrogens can be converted to N-oxides by treatment with an oxidizing agent (e.g., MCPBA and/or hydrogen peroxides) to afford other compounds of the present invention. Thus, all shown and claimed nitrogen-containing compounds are considered, when allowed by valency and structure, to include both the compound as shown and its N-oxide derivative (which can be designated as N→O or N⁺-O⁻). Furthermore, in other instances, the nitrogens in the compounds of the present invention can be converted to N-hydroxy or N-alkoxy compounds. For example, N-hydroxy compounds can be prepared by oxidation of the parent amine by an oxidizing agent such as MCPBA. All shown and claimed nitrogen-containing compounds are also considered, when allowed by valency and structure, to cover both the compound as shown and its N-hydroxy (i.e., N—OH) and N-alkoxy (i.e., N—OR, wherein R is substituted or unsubstituted C_1-6 alkyl, alkenyl, alkynyl, C_3-14 carbocycle, or 3-14-membered heterocycle) derivatives.

[0019] When an atom or chemical moiety is followed by a subscripted numeric range (e.g., C_1-6), the invention is meant to encompass each number within the range as well as all intermediate ranges. For example, “C_1-6 alkyl” is meant to include alkyl groups with 1, 2, 3, 4, 5, 6, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, and 5-6 carbons.

[0020] As used herein, “alkyl” is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. For example, C_1-6 alkyl is intended to include C₁, C₂, C₃, C₄, C₅, and C₆ alkyl groups. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, s-pentyl, and n-hexyl.

[0021] As used herein, “alkenyl” is intended to include hydrocarbon chains of either straight or branched configuration having one or more carbon-carbon double bonds occurring at any stable point along the chain. For example, C_2-6 alkenyl is intended to include C₂, C₃, C₄, C₅, and C₆ alkenyl groups. Examples of alkenyl include, but are not limited to, ethenyl and propenyl.

[0022] As used herein, “alkynyl” is intended to include hydrocarbon chains of either straight or branched configuration having one or more carbon-carbon triple bonds occurring at any stable point along the chain. For example, C_2-6 alkynyl is intended to include C₂, C₃, C₄, C₅, and C₆ alkynyl groups. Examples of alkynyl include, but are not limited to, ethynyl and propynyl.

[0023] As used herein, “halo” or “halogen” refers to fluoro, chloro, bromo, and iodo. “Counterion” is used to represent a small, negatively charged species such as chloride, bromide, hydroxide, acetate, and sulfate.

[0024] As used herein, “carbocycle” or “carbocyclic ring” is intended to mean any stable monocyclic, bicyclic, or tricyclic ring having the specified number of carbons, any of which may be saturated, unsaturated, or aromatic. For example a C_3-14 carbocycle is intended to mean a mono-, bi-, or tricyclic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 carbon atoms. Examples of carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cycloheptenyl, cycloheptyl, cycloheptenyl, adamantyl, cyclooctyl, cyclooctenyl, cyclooctadienyl, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, and tetrahydronaphthyl. Bridged rings are also included in the definition of carbocycle, including, for example, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane, and [2.2.2]bicyclooctane. A bridged ring occurs when one or more carbon atoms link two non-adjacent carbon atoms. Preferred bridges are one or two carbon atoms. It is noted that a bridge always converts a monocyclic ring into a tricyclic ring. When a ring is bridged, the substituents recited for the ring may also be present on the bridge. Fused (e.g., naphthyl and tetrahydronaphthyl) and spiro rings are also included.

[0025] As used herein, the term “heterocycle” or “heterocyclic” is intended to mean any stable monocyclic, bicyclic, or tricyclic ring which is saturated, unsaturated, or aromatic and comprises carbon atoms and one or more ring heteroatoms, e.g., 1 or 1-2 or 1-3 or 1-4 or 1-5 or 1-6 heteroatoms, independently selected from the group consisting of nitrogen, oxygen, and sulfur. A bicyclic or tricyclic heterocycle may have one or more heteroatoms located in one ring, or the heteroatoms may be located in more than one ring. The nitrogen and sulfur heteroatoms may optionally be oxidized (i.e., N→O and S(O)_p, where p=1 or 2). When a nitrogen atom is included in the ring it is either N or NH, depending on whether or not it is attached to a double bond in the ring (i.e., a hydrogen is present if needed to maintain the tri-valency of the nitrogen atom). The nitrogen atom may be substituted or unsubstituted (i.e., N or NR wherein R is H or another substituent, as defined). The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. A nitrogen in the heterocycle may optionally be quaternized. It is preferred that when the total number of S and O atoms in the heterocycle exceeds 1, then these heteroatoms are not adjacent to one another. Bridged rings are also included in the definition of heterocycle. A bridged ring occurs when one or more atoms (i.e., C, O, N, or S) link two non-adjacent carbon or nitrogen atoms. Preferred bridges include, but are not limited to, one carbon atom, two carbon atoms, one nitrogen atom, two nitrogen atoms, and a carbon-nitrogen group. It is noted that a bridge always converts a monocyclic ring into a tricyclic ring. When a ring is bridged, the substituents recited for the ring may also be present on the bridge. Spiro and fused rings are also included.

[0026] As used herein, the term “aromatic heterocycle” or “heteroaryl” is intended to mean a stable 5, 6, or 7-membered monocyclic or bicyclic aromatic heterocyclic ring or 7, 8, 9, 10, 11, or 12-membered bicyclic aromatic heterocyclic ring which consists of carbon atoms and one or more heteroatoms, e.g., 1 or 1-2 or 1-3 or 1-4 or 1-5 or 1-6 heteroatoms, independently selected from the group consisting of nitrogen, oxygen, and sulfur. In the case of bicyclic heterocyclic aromatic rings, only one of the two rings needs to be aromatic (e.g., 2,3-dihydroindole), though both may be (e.g., quinoline). The second ring can also be fused or bridged as defined above for heterocycles. The nitrogen atom may be substituted or unsubstituted (i.e., N or NR wherein R is H or another substituent, as defined). The nitrogen and sulfur heteroatoms may optionally be oxidized (i.e., N→O and S(O)_p, where p=1 or 2). It is to be noted that total number of S and O atoms in the aromatic heterocycle is not more than 1.

[0027] Examples of heterocycles include, but are not limited to, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, methylenedioxyphenyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, piperidonyl, 4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1 ,3,4-triazolyl, and xanthenyl.

[0028] As used herein, the phrase “pharmaceutically acceptable” refers to those compounds, materials, compositions, carriers, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.

[0029] As used herein, “pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines, alkali or organic salts of acidic residues such as carboxylic acids, and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids selected from 2-acetoxybenzoic, 2-hydroxyethane sulfonic, acetic, ascorbic, benzene sulfonic, benzoic, bicarbonic, carbonic, citric, edetic, ethane disulfonic, ethane sulfonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic, hydrabamic, hydrobromic, hydrochloric, hydroiodic, hydroxymaleic, hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulfonic, maleic, malic, mandelic, methane sulfonic, napsylic, nitric, oxalic, pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic, propionic, salicyclic, stearic, subacetic, succinic, sulfamic, sutfanilic, sulfuric, tannic, tartaric, and toluene sulfonic.

[0030] The pharmaceutically acceptable salts of the present invention can be synthesized from a parent compound that contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, non-aqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 18th ed. (Mack Publishing Company, 1990).

[0031] Since prodrugs are known to enhance numerous desirable qualities of pharmaceuticals (e.g., solubility, bioavailability, manufacturing, etc.) the compounds of the present invention may be delivered in prodrug form. Thus, the present invention is intended to cover prodrugs of the presently claimed compounds, methods of delivering the same and compositions containing the same. “Prodrugs” are intended to include any covalently bonded carriers that release an active parent drug of the present invention in vivo when such prodrug is administered to a mammalian subject. Prodrugs the present invention are prepared by modifying functional groups present in the compound in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound. Prodrugs include compounds of the present invention wherein a hydroxy, amino, or sulfhydryl group is bonded to any group that, when the prodrug of the present invention is administered to a mammalian subject, cleaves to form a free hydroxyl, free amino, or free sulfhydryl group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate, and benzoate derivatives of alcohol and amine functional groups in the compounds of the present invention.

[0032] “Stable compound” and “stable structure” are meant to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.

[0033] As used herein, “treating” or “treatment” means the treatment of a disease-state in a mammal, particularly in a human, and include: (a) preventing the disease-state from occurring in a mammal, in particular, when such mammal is predisposed to the disease-state but has not yet been diagnosed as having it; (b) inhibiting the disease-state, i.e., arresting its development; and/or (c) relieving the disease-state, i.e., causing regression of the disease state.

[0034] As used herein, “mammal” refers to human and non-human patients.

[0035] As used herein, the term “effective amount” refers to an amount of a compound, or a combination of compounds, of the present invention effective when administered alone or in combination as an anti-proliferative and/or anti-infective agent. The combination of compounds is preferably a synergistic combination. Synergy, as described, for example, by Chou and Talalay, Adv. Enzyme Regul. 1984, 22:27-55, occurs when the effect of the compounds when administered in combination is greater than the additive effect of the compounds when administered alone as a single agent. In general, a synergistic effect is most clearly demonstrated at sub-optimal concentrations of the compounds. Synergy can be in terms of lower cytotoxicity, increased anti-proliferative and/or anti-infective effect, or some other beneficial effect of the combination compared with the individual components.

[0036] All percentages and ratios used herein, unless otherwise indicated, are by weight.

[0037] Throughout the description, where compositions are described as having, including, or comprising specific components, it is contemplated that compositions also consist essentially of, or consist of, the recited components. Similarly, where processes are described as having, including, or comprising specific process steps, the processes also consist essentially of, or consist of, the recited processing steps. Further, it should be understood that the order of steps or order for performing certain actions are immaterial so long as the invention remains operable. Moreover, two or more steps or actions may be conducted simultaneously.

2. Compounds of the Invention

[0038] In one aspect, the invention provides compounds having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein:

[0039] A is selected from the group consisting of:

• • [0040] phenyl, pyridyl, pyrazinyl, pyrimidinyl, and pyridazinyl;

[0041] B is selected from the group consisting of:

• • [0042] phenyl, pyridyl, pyrazinyl, pyrimidinyl, and pyridazinyl;

[0043] Het-CH₂-R³ is selected from the group consisting of:

[0044] M is selected from the group consisting of:

• • [0045] a) saturated, unsaturated, or aromatic C_3-14 carbocycle, and b) saturated, unsaturated, or aromatic 3-14 membered heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
    • [0046] wherein a) or b) optionally is substituted with one or more R⁵ groups;

[0047] M-L is selected from the group consisting of:

• • [0048] a) M-X, b) M-L¹, c) M-L¹-X, d) M-X-L², e) M-L¹-X-L², f) M-X-L¹-X-L², g) M-L¹-X-L²-X, h) M-X-X-, i) M-L¹-X-X-, j) M-X-X-L², and k) M-L¹-X-X-L², wherein

[0049] X, at each occurrence, independently is selected from the group consisting of:

• • [0050] a) —O—, b) —NR⁴—, c) —N(O)—, d) —N(OR⁴)—, e) —S(O)_p—, f) —SO₂NR⁴—, g) —NR⁴SO₂—, h) —NR⁴—N═, i) ═N—NR⁴—, j) —O—N═, k) ═N—O—, l) —N═, m) ═N—, n) —NR⁴-NR⁴—, o) —NR⁴C(O)O—, p) —OC(O)NR⁴—, q) —NR⁴C(O)NR⁴— r) —NR⁴C(NR⁴)NR⁴—, and s)

[0051] L¹ is selected from the group consisting of:

• • [0052] a) C_1-6 alkyl, b) C_2-6 alkenyl, and c) C_2-6 alkynyl,
    • [0053] wherein any of a)-c) optionally is substituted with one or more R⁵ groups; and

[0054] L² is selected from the group consisting of:

• • [0055] a) C_1-6 alkyl, b) C_2-6 alkenyl, and c) C_2-6 alkynyl,
    • [0056] wherein any of a)-c) optionally is substituted with one or more R⁵ groups;

[0057] R¹, at each occurrence, independently is selected from the group consisting of:

• • [0058] a) F, b) Cl, c) Br, d) I, e) —CF₃, f) —OR⁴, g) —CN, h) —NO₂, i) —NR⁴R⁴, j) —C(O)R⁴, k) —C(O)OR⁴, l) —OC(O)R⁴, m) —C(O)NR⁴R⁴, n) —NR⁴C(O)R⁴, o) —OC(O)NR⁴R⁴, p) —NR⁴C(O)OR⁴, q) —NR⁴C(O)NR⁴R⁴, r) —C(S)R⁴, s) —C(S)OR⁴, t) —OC(S)R⁴, u) —C(S)NR⁴R⁴, v) —NR⁴C(S)R⁴, w) —OC(S)NR⁴R⁴, x) —NR⁴C(S)OR⁴, y) —NR⁴C(S)NR⁴R⁴, z) —NR⁴C(NR⁴)NR⁴R⁴, aa) —S(O)_pR⁴, bb) —SO₂NR⁴R⁴, and cc) R⁴;

[0059] R², at each occurrence, independently is selected from the group consisting of:

• • [0060] a) F, b) Cl, c) Br, d) I, e) —CF₃, f) —OR⁴, g) —CN, h) —NO₂, i) —NR⁴R⁴, j) —C(O)R⁴, k) —C(O)OR⁴, l) —OC(O)R⁴, m) —C(O)NR⁴R⁴, n) —NR⁴C(O)R⁴, o) —OC(O)NR⁴R⁴, p) —NR⁴C(O)OR⁴, q) —NR⁴C(O)NR⁴R⁴, r) —C(S)R⁴, s) —C(S)OR⁴, t) —OC(S)R⁴, u) —C(S)NR⁴R⁴, v) —NR⁴C(S)R⁴, w) —OC(S)NR⁴R⁴, x) —NR⁴C(S)OR⁴, y) —NR⁴C(S)NR⁴R⁴, z) —NR⁴C(NR⁴)NR⁴R⁴, aa) —S(O)_pR⁴, bb) —SO₂NR⁴R⁴, and cc) R⁴;

[0061] R³ is selected from the group consisting of:

• • [0062] a) —OR⁴, b) —NR⁴R⁴, c) —C(O)R⁴, d) —C(O)OR⁴, e) —OC(O)R⁴, f) —C(O)NR⁴R⁴, g) —NR⁴C(O)R⁴, h) —OC(O)NR⁴R⁴, i) —NR⁴C(O)OR⁴, j) —NR⁴C(O)NR⁴R⁴, k) —C(S)R⁴, l) —C(S)OR⁴, m) —OC(S)R⁴, n) —C(S)NR⁴R⁴, o) —NR⁴C(S)R⁴, p) —OC(S)NR⁴R⁴, q) —NR⁴C(S)OR⁴, r) —NR⁴C(S)NR⁴R⁴, s) —NR⁴C(NR⁴)NR⁴R⁴, t) —S(O)_pR⁴, u) —SO₂NR⁴R⁴, and v) R⁴;

[0063] R⁴, at each occurrence, independently is selected from the group consisting of:

• • [0064] a) H, b) C_1-6 alkyl, c) C_2-6 alkenyl, d) C_2-6 alkynyl, e) C_3-14 saturated, unsaturated, or aromatic carbocycle, f) 3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfir, g) —C(O)—C_1-6 alkyl, h) —C(O)—C_2-6 alkenyl, i) —C(O)—C_2-6 alkynyl, j) —C(O)—C_3-14 saturated, unsaturated, or aromatic carbocycle, k) —C(O)-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, l) —C(O)O—C_1-6 alkyl, m) —C(O)O—C_2-6 alkenyl, n) —C(O)O—C_2-6 alkynyl, o) —C(O)O—C_3-14 saturated, unsaturated, or aromatic carbocycle, and p) —C(O)O-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
    • [0065] wherein any of b)-p) optionally is substituted with one or more R⁵ groups;

[0066] R⁵, at each occurrence, is independently selected from the group consisting of:

• • [0067] a) F, b) Cl, c) Br, d) I, e) ═O, f) ═S, g) ═NR⁶, h) ═NOR⁶, i) ═N—NR⁶R⁶, j) —CF₃, k) —OR⁶, l) —CN, m) —NO₂, n) —NR⁶R⁶, o) —C(O)R⁶, p) —C(O)OR⁶, q) —OC(O)R⁶, r) —C(O)NR⁶R⁶, s) —NR⁶C(O)R⁶, t) —OC(O)NR⁶R⁶, u) —NR⁶C(O)OR⁶, v) —NR⁶C(O)NR⁶R⁶, w) —C(S)R⁶, x) —C(S)OR⁶, y) —OC(S)R⁶, z) —C(S)NR⁶R⁶, aa) —NR⁶C(S)R⁶, bb) —OC(S)NR⁶R⁶, cc) —NR⁶C(S)OR⁶, dd) —NR⁶C(S)NR⁶R⁶, ee) —NR⁶C(NR)NR⁶R⁶, ff) —S(O)_pR⁶, gg) —SO₂NR⁶R⁶, and hh) R⁶;

[0068] R⁶, at each occurrence, independently is selected from the group consisting of:

[0069] a) H, b) C_1-6 alkyl, c) C_2-6 alkenyl, d) C_2-6 alkynyl, e) C_3-14 saturated, unsaturated, or aromatic carbocycle, f) 3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, g) —C(O)—C_1-6 alkyl, h) —C(O)—C_2-6 alkenyl, i) —C(O)—C_2-6 alkynyl, j) —C(O)—C_3-14 saturated, unsaturated, or aromatic carbocycle, k) —C(O)-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, l) —C(O)O—C_1-6 alkyl, m) —C(O)O—C_2-6 alkenyl, n) —C(O)O—C_2-6 alkynyl, o) —C(O)O—C_3-14 saturated, unsaturated, or aromatic carbocycle, and p) —C(O)O-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,

• • • [0070] wherein any of b)-p) optionally is substituted with one or more R⁷ groups;

[0071] R⁷, at each occurrence, independently is selected from the group consisting of:

• • [0072] a) F, b) Cl, c) Br, d) I, e) ═O, f) ═S, g) ═NR⁸, h) ═NOR⁸, i) ═N—NR⁸R⁸, j) —CF₃, k) —OR⁸, l) —CN, m) —NO₂, n) —NR⁸R⁸, o) —C(O)R⁸, p) —C(O)OR⁸, q) —OC(O)R⁸, r) —C(O)NR⁸R⁸, s) —NR⁸C(O)R⁸, t) —OC(O)NR⁸R⁸, u) —NR⁸C(O)OR⁸, v) —NR⁸C(O)NR⁸R⁸, w) —C(S)R⁸, x) —C(S)OR⁸, y) —OC(S)R⁸, z) —C(S)NR⁸R⁸, aa) —NR⁸C(S)R⁸, bb) —OC(S)NR⁸R⁸, cc) —NR⁸C(S)OR⁸, dd) —NR⁸C(S)NR⁸R⁸, ee) —NR⁸C(NR⁸)NR⁸R⁸, ff) —S(O)_pR⁸, gg) —SO₂NR⁸R⁸, hh) C_1-6 alkyl, ii) C_2-6 alkenyl, jj) C_2-6 alkynyl, kk) C_3-14 saturated, unsaturated, or aromatic carbocycle, and ll) 3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
    • [0073] wherein any of hh)-ll) optionally is substituted with one or more moieties selected from the group consisting of R⁸, F, Cl, Br, I, —CF₃, —OR⁸, —SR⁸, —CN, —NO₂, —NR⁸R⁸, —C(O)R⁸, —C(O)OR⁸, —OC(O)R⁸, —C(O)NR⁸R⁸, —NR⁸C(O)R⁸, —OC(O)NR⁸R⁸, —NR⁸C(O)OR⁸, —NR⁸C(O)NR⁸R⁸, —C(S)R⁸, —C(S)OR⁸, —OC(S)R⁸, —C(S)NR⁸R⁸, —NR⁸C(S)R⁸, —OC(S)NR⁸R⁸, —NR⁸C(S)OR⁸, —NR⁸C(S)NR⁸R⁸, —NR⁸C(NR⁸)NR⁸R⁸, —SO₂NR⁸R⁸, and —S(O)_pR⁸;

[0074] R⁸, at each occurrence, independently is selected from the group consisting of:

• • [0075] a) H, b) C_1-6 alkyl, c) C_2-6 alkenyl, d) C_2-6 alkynyl, e) C_3-14 saturated, unsaturated, or aromatic carbocycle, f) 3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, g) —C(O)—C_1-6 alkyl, h) —C(O)—C_2-6 alkenyl, i) —C(O)—C_2-6 alkynyl, j) —C(O)—C_3-14 saturated, unsaturated, or aromatic carbocycle, k) —C(O)-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, l) —C(O)O—C_1-6 alkyl, m) —C(O)O—C_2-6 alkenyl, n) —C(O)O—C_2-6 alkynyl, o) —C(O)O—C_3-14 saturated, unsaturated, or aromatic carbocycle, and p) —C(O)O-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
    • [0076] wherein any of b)-p) optionally is substituted with one or more moieties selected from the group consisting of F, Cl, Br, I, —CF₃, —OH, —OCH₃, —SH, —SCH₃, —CN, —NO₂, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)CH₃, —C(O)OCH₃, —C(O)NH₂, —NHC(O)CH₃, —SO₂NH₂, —SO₂NHCH₃, —SO₂N(CH₃)₂, and —S(O)_pCH₃;

[0077] m is 0, 1, 2, 3, or 4;

[0078] n is 0, 1, 2, 3, or 4; and

[0079] p, at each occurrence, independently is 0, 1, or 2,

and wherein the compound does not have the formula corresponding to any of the structures listed in Table 1.

[0080]

TABLE 1

[0081] Particular embodiments of the invention include compounds having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein A, B, L, M, R¹, R², R³, m, and n are defined above.

[0082] Other embodiments include compounds having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein A, B, L, M, R¹, R², R³, m, and n are defined as described above.

[0083] Particular compounds include those where A is selected from the group consisting of phenyl and pyridyl; B is selected from the group consisting of phenyl and pyridyl; m is 0, 1, or 2; and n is 0, 1, or 2.

[0084] In some embodiments, A-B is:
wherein A, R², and n are defined as described above. In particular embodiments, A-B is:
wherein A is defined as described above.

[0085] In various embodiments, A-B is:
wherein B is defined as described in above.

[0086] In some embodiments, R³ is —NHC(O)R⁴. Particular compounds according to these embodiments include those where R⁴ is —CH₃ or

[0087] Particular embodiments of the invention include compounds having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein A, B, L, M, R¹, R², m, and n are defined as described above.

[0088] Other embodiments of the invention include compounds having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein A, L, M, R¹, R³, and m are defined as described above.

[0089] Still other embodiments of the invention include compounds having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein A, L, M, R¹, and m are defined as described above.

[0090] Some embodiments of the invention include compounds having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein L, M, and R³ are defined as described above. Particular compounds according to these embodiments include those wherein R³ is —NHC(O)CH₃.

[0091] Other embodiments of the invention include compounds having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein A, L, M, R¹, R³, and m are defined as described above.

[0092] Still other embodiments of the invention include compounds having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein A, L, M, R¹, and m are defined as described above.

[0093] Some embodiments of the invention include compounds having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein L, M, and R³ are defined as described above. Particular compounds according to these embodiments include those wherein R³ is —NHC(O)CH₃.

[0094] In some embodiments, M-L is M-L¹, and L¹ is C_1-6 alkyl. In particular embodiments, M-L¹ is M—CH₂—.

[0095] In other embodiments, M-L is M-L¹-X-L², and X is —NR⁴—. In particular compounds according to these embodiments, X is —NH—, —N(O)—, or —N(OR⁴)—, where R⁴ is H or C_1-6 alkyl. Other compounds include those where X is
In certain compounds according to these embodiments, L¹ is C_1-6 alkyl, and L² is C_1-6 alkyl. In some embodiments, L¹ is —CH₂— and L² is —CH₂—. Particular examples of compounds according to these embodiments include those where M-L is M—CH₂—NH—CH₂— or

[0096] In still other embodiments, M-L is M—S—L¹—NR⁴—L², wherein L¹ is C_1-6 alkyl, and L² is C_1-6 alkyl. In particular compounds according to these embodiments, M-L is M—S—CH₂CH₂—NH—CH₂—.

[0097] In particular embodiments, M is selected from the group consisting of:

• • [0098] a) phenyl, b) pyridyl, c) pyrazinyl, d) pyrimidinyl, e) pyridazinyl, f) oxiranyl, g) aziridinyl, h) furanyl, i) thiophenyl, j) pyrrolyl, k) oxazolyl, l) isoxazolyl, m) imidazolyl, n) pyrazolyl, o) isothiazolyl, p) thiazolyl, q) triazolyl, r) tetrazolyl, s) indolyl, t) purinyl, u) benzofuranyl, v) benzoxazolyl, w) benzisoxazolyl, x) quinolinyl, y) isoquinolinyl, z) quinoxalinyl, aa) quinazolinyl, bb) cinnolinyl, cc) cyclopropyl, dd) cyclobutyl, ee) cyclopentyl, ff) cyclohexyl, gg) cycloheptyl, hh) oxetanyl, ii) tetrahydrofuranyl, jj) tetrahydropyranyl, kk) azetidinyl, ll) pyrrolidinyl, mm) piperidinyl, nn) thietanyl, oo) tetrahydrothiophenyl, pp) tetrahydrothiopyranyl, qq) piperazinyl, rr) quinuclidinyl, ss) 1-azabicyclo[2.2.1]hyeptanyl, tt) morpholinyl, uu) thiomorpholinyl, vv) thiooxomorpholinyl, ww) thiodioxomorpholinyl, and xx) benzothiophenyl
    wherein any of a)-xx) optionally is substituted with one or more R⁵ groups. In particular embodiments, M is 4-isoxazolyl, [1,2,3]triazol-1-yl, 3H-[1,2,3]triazol-4-yl, 1H-tetrazol-5-yl, piperidin-1-yl, or pyrolidin-1-yl.

[0099] In preferred embodiments, A is phenyl, substituted phenyl, pyridyl, or substituted pyridyl. Under certain circumstances, when A is pyridin-4-yl substituted with M-L at the 2 position, M-L is not (imidazol-1-yl)methyl or (morpholin-4-yl)methyl.

[0100] In preferred embodiments, B is phenyl or substituted phenyl. More preferably, B is substituted phenyl. Preferred substituents include halogens, and in particular, fluorine. Under certain circumstances, when B is unsubstituted phenyl, M-L is selected from the group consisting of M-X, M-L¹-X, M-L¹-X-L², M-X-L¹-X-L², M-X-X-, M-L¹-X-X-, M-X-X-L², and M-L¹-X-X-L². Under certain circumstances, when B is pyridin-2-yl substituted with A at the 5 position, M-L is selected from the group consisting of M-X, M-L¹-X, M-L¹-X-L², M-L¹-X-L²-X, M-X-X-, M-X-X-L², and M-L¹-X-X-L².

[0101] In another aspect, the invention provides a pharmaceutical composition comprising an effective amount of one or more of the foregoing compounds and a pharmaceutically acceptable carrier. Suitable formulating agents are described in detail in section 5 hereinbelow.

[0102] One or more of the foregoing compounds may also be incorporated into a medical device. For example, a medical device, such as a medical stent, can contain or be coated with one or more of the compounds of the invention.

[0103] In another aspect, the invention provides a method for treating a microbial infection, a fungal infection, a viral infection, a parasitic disease, a proliferative disease, an inflammatory disease, or a gastrointestinal motility disorder in a mammal. The method involves administering an effective amount of one or more compounds or pharmaceutical compositions of the invention, for example, via oral, parenteral or topical routes.

[0104] The invention provides a method of treating a disorder in a mammal comprising the step of administering to the mammal an effective amount of one or more compounds of the invention thereby to ameliorate a symptom of a particular disorder. Such a disorder can be selected from the group consisting of a skin infection, nosocomial pneumonia, post-viral pneumonia, an abdominal infection, a urinary tract infection, bacteremia, septicemia, endocarditis, an atrio-ventricular shunt infection, a vascular access infection, meningitis, surgical prophylaxis, a peritoneal infection, a bone infection, a joint infection, a methicillin-resistant Staphylococcus aureus infection, a vancomycin-resistant Enterococci infection, a linezolid-resistant organism infection, and tuberculosis.

3. Synthesis of the Compounds of the Invention

[0105] The invention provides methods and intermediates for making compounds of the present invention. The following schemes depict some exemplary chemistries available for synthesizing the compounds of the invention. It will be appreciated, however, that the desired compounds may be synthesized using other alternative chemistries known in the art.

[0106] The following examples illustrate some of the compounds of the present invention. Compounds of general structures Ia through IVb (wherein X is CH or N) can be synthesized by the chemistries exemplified below in the following schemes.

[0107] Scheme A exemplifies the synthesis of biaryl amine intermediate 5, which is useful in producing certain compounds of the present invention. Known iodoaryl oxazolidinone intermediate 1 (see U.S. Pat. Nos. 5,523,403 and 5,565,571) is coupled to a substituted aryl boronic acid (the Suzuki reaction) to produce biaryl alcohol 2. Other coupling reactions (for example, the Stille reaction) using alternate coupling intermediates easily obtained or synthesized by those skilled in the art could also be employed to synthesize target biaryl intermediates similar to 2. These alternate coupling reactions are within the scope of the present invention. Alcohol 2 is then converted to amine 5 by chemistry well known to those skilled in the art.

[0108] Scheme B illustrates the synthesis of intermediates 7 and 8 of the present invention using Suzuki coupling chemistry between boronic acids and aryl triflates. Boronic ester 6 is treated with an appropriate aryl triflate to yield the BOC-protected biaryl 7. The BOC group of 7 is removed to provide amine 8, an intermediate useful in the synthesis of certain compounds of the present invention.

[0109] Scheme C depicts the synthesis of intermediates 9-13, which are useful in producing certain methoxy-substituted biaryl derivatives of the present invention. Suzuki coupling of boronic ester 6 produces biaryl aldehyde 9, which can be reduced to alcohol 10. Mesylation of 10 yields 11 that can be converted to azide 12. Reduction of azide 12 yields amine 13.

[0110] Scheme D depicts the synthesis of pyridyl intermediates, which are useful for the synthesis of compounds of the present invention, via similar chemistry to that shown in Scheme C. Coupling of boronic ester 6 to a halopyridine aldehyde produces biaryl aldehyde 14. Aldehyde 14 serves as the precursor to intermediates 15-18 via chemistry described above.

[0111] Biaryl aldehyde 19 (Scheme E) can be synthesized from a Suzuki coupling of iodide 1 and 4-formylphenylboronic acid. Scheme E illustrates how intermediate aldehydes of type 19, 9, and 14 can be converted via reductive amination chemistry to other amines, such as amines 20-22, which are useful as intermediates for the synthesis of certain compounds of the invention.

[0112] Scheme F depicts the general synthesis of compounds of type Ia and Ib from amines of type 5, 13, 18, and 20-22. Compounds of type Ia and Ib are synthesized via acylation of amines 5, 13 and 18 and 20-22 with the appropriate acids using, for example, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) as the coupling agent. Compounds 4001-4007 were specifically synthesized from amine 5 and the appropriate carboxylic acids.

[0113] Scheme G highlights the synthesis of compounds of general structure II from amines of type 5 and 18. The amine can be acylated with carboxylic acids using EDCI (or other commonly employed peptide coupling reagents known in the art) to afford amides II. Acid chlorides can be purchased or synthesized and allowed to react with amines 5 and 18, in the presence of bases such as triethylamine, to also produce amides II. Alternatively, carboxylic acids can be pre-loaded onto a solid polymeric support, such as a tetrafluorophenol containing resin (TFP resin), and reacted with amines to yield amide products of general structure II (such as compounds 4008-4015).

[0114] Scheme H illustrates the synthesis of compounds of general structure IIIa from amines of type 5, 13, and 18 using reductive amination chemistry. For example, biaryl amine compounds 4016-4028 are synthesized in this manner.

[0115] Scheme I depicts the synthesis of general structure IIIb of the present invention from amine intermediate 8. For example, compounds 4029-4031 are synthesized using this reductive amination chemistry.

[0116] Scheme J shows the synthesis of compounds of general structure IVa and IVb. Amines 20, 21, and 22 can be converted to tertiary amines IVa, such as compounds 4032-4034 and 4036, using standard reductive amination chemistry employed earlier for other derivatives. This reductive amination chemistry can be employed on biaryl aldehyde intermediates such as 19, 9, and 14 to yield optionally substituted amines of general structure IVb, illustrated by compound 4037.

[0117] It should be noted that, when X is N, any of the synthetic routes described above may be used to produce compounds having any regioisomer of pyridine (e.g., pyridin-2-yl or pyridin-3-yl).

[0118] In addition, the invention provides alternative approaches for synthesizing compounds of the invention. In one approach, the method includes the step of combining a compound of formula (I):
with a compound of formula (II):
in a solvent in the presence of a base and a palladium catalyst, wherein

[0119] Q is a boronate having the formula —BY₂, wherein

• • [0120] Y, at each occurrence, independently is selected from the group consisting of:
    • [0121] a) —OH, and b) —O—C_1-4 alkyl, alternatively, two Y groups taken together are selected from the group consisting of:
    • [0122] a) —OC(R⁴)(R⁴)C(R⁴)(R⁴)O—, and b) —OC(R⁴)(R⁴)CH₂C(R⁴)(R⁴)O—, alternatively, two Y groups taken together with the boron to which they are bound comprise a BF₃ alkali metal salt;

[0123] Z is selected from the group consisting of:

• • [0124] a) I, b) Br, c) Cl, and d) R⁴OSO₃—; and
  • [0125] A, B, Het, L, M, R¹, R², R³, R⁴, m, and n are defined as described above.

[0126] In another approach, the method includes the step of combining a compound of formula (III):
with a compound of formula (IV):
in a solvent in the presence of a base and a palladium catalyst, wherein A, B, Het, L, M, R¹, R², R³, R⁴, Q, Z, m, and n are defined as described above.

[0127] In either approach, Z can be I. Furthermore, Q can be —BF₂·KF or

[0128] In some embodiments, the base is selected from the group consisting of an alkali metal hydroxide, an alkali metal carbonate, an alkali metal fluoride, a trialkyl amine, and mixtures thereof. Examples of suitable bases include potassium carbonate, sodium carbonate, potassium fluoride, triethylamine, diisopropylethylamine, and mixtures thereof. In particular embodiments, the ratio of equivalents of base to equivalents of compound (I) or compound (III) is about 3:1.

[0129] In some embodiments, the palladium catalyst is a ligand coordinated palladium (0) catalyst, such as a tetrakis(trialkylphosphine) palladium (0) or a tetrakis(triarylphosphine) palladium (0) catalyst. An example of a suitable palladium catalyst is tetrakis(triphenylphosphine) palladium (0). In particular embodiments, the ratio of the equivalents of tetrakis(triphenylphosphine) palladium (0) to the equivalents of compound (I) or compound (III) is about 1:20.

[0130] In some embodiments, the solvent comprises an aqueous solvent. In other embodiments, the solvent comprises a mixture of water and an organic solvent, wherein the organic solvent is selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, isobutanol, secondary butanol, tertiary butanol, benzene, toluene, tetrahydrofuran, dimethylformamide, 1,2-diethyl ether, dimethoxyethane, diisopropyl ether, methyltertiarybutyl ether, methoxymethyl ether, 2-methoxyethyl ether, 1,4-dioxane, 1,3-dioxolane, and mixtures thereof. In a particular embodiment, the solvent is a mixture of water, toluene, and ethanol in a ratio, for example, of about 1:3:1 by volume.

[0131] In some embodiments, the method is carried out at a temperature between about 20° C. and about 100° C. In other embodiments, the process is carried out at the reflux temperature of the solvent.

4. Characterization of Compounds of the Invention

[0132] Compounds designed, selected and/or optimized by methods described above, once produced, may be characterized using a variety of assays known to those skilled in the art to determine whether the compounds have biological activity. For example, the molecules may be characterized by conventional assays, including but not limited to those assays described below, to determine whether they have a predicted activity, binding activity and/or binding specificity.

[0133] Furthermore, high-throughput screening may be used to speed up analysis using such assays. As a result, it may be possible to rapidly screen the molecules described herein for activity, for example, as anti-cancer, anti-bacterial, anti-fungal, anti-parasitic or anti-viral agents. Also, it may be possible to assay how the compounds interact with a ribosome or ribosomal subunit and/or are effective as modulators (for example, inhibitors) of protein synthesis using techniques known in the art. General methodologies for performing high-throughput screening are described, for example, in Devlin, High Throughput Screening, (Marcel Dekker, 1998); and U.S. Pat. No. 5,763,263. High-throughput assays can use one or more different assay techniques including, but not limited to, those described below.

[0134] (1) Surface Binding Studies. A variety of binding assays may be useful in screening new molecules for their binding activity. One approach includes surface plasmon resonance (SPR) that can be used to evaluate the binding properties of molecules of interest with respect to a ribosome, ribosomal subunit or a fragment thereof.

[0135] SPR methodologies measure the interaction between two or more macromolecules in real-time through the generation of a quantum-mechanical surface plasmon. One device, (BIAcore Biosensor RTM from Pharmacia Biosensor, Piscatawy, N.J.) provides a focused beam of polychromatic light to the interface between a gold film (provided as a disposable biosensor “chip”) and a buffer compartment that can be regulated by the user. A 100 nm thick “hydrogel” composed of carboxylated dextran that provides a matrix for the covalent immobilization of analytes of interest is attached to the gold film. When the focused light interacts with the free electron cloud of the gold film, plasmon resonance is enhanced. The resulting reflected light is spectrally depleted in wavelengths that optimally evolved the resonance. By separating the reflected polychromatic light into its component wavelengths (by means of a prism), and determining the frequencies that are depleted, the BIAcore establishes an optical interface which accurately reports the behavior of the generated surface plasmon resonance. When designed as above, the plasmon resonance (and thus the depletion spectrum) is sensitive to mass in the evanescent field (which corresponds roughly to the thickness of the hydrogel). If one component of an interacting pair is immobilized to the hydrogel, and the interacting partner is provided through the buffer compartment, the interaction between the two components can be measured in real time based on the accumulation of mass in the evanescent field and its corresponding effects of the plasmon resonance as measured by the depletion spectrum. This system permits rapid and sensitive real-time measurement of the molecular interactions without the need to label either component.

[0136] (2) Fluorescence Polarization. Fluorescence polarization (FP) is a measurement technique that can readily be applied to protein-protein, protein-ligand, or RNA-ligand interactions in order to derive IC_50S and Kds of the association reaction between two molecules. In this technique one of the molecules of interest is conjugated with a fluorophore. This is generally the smaller molecule in the system (in this case, the compound of interest). The sample mixture, containing both the ligand-probe conjugate and the ribosome, ribosomal subunit or fragment thereof, is excited with vertically polarized light. Light is absorbed by the probe fluorophores, and re-emitted a short time later. The degree of polarization of the emitted light is measured. Polarization of the emitted light is dependent on several factors, but most importantly on viscosity of the solution and on the apparent molecular weight of the fluorophore. With proper controls, changes in the degree of polarization of the emitted light depends only on changes in the apparent molecular weight of the fluorophore, which in-turn depends on whether the probe-ligand conjugate is free in solution, or is bound to a receptor. Binding assays based on FP have a number of important advantages, including the measurement of IC_50S and Kds under true homogenous equilibrium conditions, speed of analysis and amenity to automation, and ability to screen in cloudy suspensions and colored solutions.

[0137] (3) Protein Synthesis. It is contemplated that, in addition to characterization by the foregoing biochemical assays, the compound of interest may also be characterized as a modulator (for example, an inhibitor of protein synthesis) of the functional activity of the ribosome or ribosomal subunit.

[0138] Furthermore, more specific protein synthesis inhibition assays may be performed by administering the compound to a whole organism, tissue, organ, organelle, cell, a cellular or subcellular extract, or a purified ribosome preparation and observing its pharmacological and inhibitory properties by determining, for example, its inhibition constant (IC₅₀) for inhibiting protein synthesis. Incorporation of ³H leucine or ³⁵S methionine, or similar experiments can be performed to investigate protein synthesis activity. A change in the amount or the rate of protein synthesis in the cell in the presence of a molecule of interest indicates that the molecule is a modulator of protein synthesis. A decrease in the rate or the amount of protein synthesis indicates that the molecule is a inhibitor of protein synthesis.

[0139] Furthermore, the compounds may be assayed for anti-proliferative or anti-infective properties on a cellular level. For example, where the target organism is a microorganism, the activity of compounds of interest may be assayed by growing the microorganisms of interest in media either containing or lacking the compound. Growth inhibition may be indicative that the molecule may be acting as a protein synthesis inhibitor. More specifically, the activity of the compounds of interest against bacterial pathogens may be demonstrated by the ability of the compound to inhibit growth of defined strains of human pathogens. For this purpose, a panel of bacterial strains can be assembled to include a variety of target pathogenic species, some containing resistance mechanisms that have been characterized. Use of such a panel of organisms permits the determination of structure-activity relationships not only in regards to potency and spectrum, but also with a view to obviating resistance mechanisms. The assays may be performed in microtiter trays according to conventional methodologies as published by The National Committee for Clinical Laboratory Standards (NCCLS) guidelines (NCCLS. M7-A5-Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard-Fifth Edition. NCCLS Document M100-S12/M7 (ISBN 1-56238-394-9)).

5. Formulation and Administration

[0140] The compounds of the invention may be useful in the prevention or treatment of a variety of human or other animal disorders, including for example, bacterial infection, fungal infections, viral infections, parasitic diseases, and cancer. It is contemplated that, once identified, the active molecules of the invention may be incorporated into any suitable carrier prior to use. The dose of active molecule, mode of administration and use of suitable carrier will depend upon the intended recipient and target organism. The formulations, both for veterinary and for human medical use, of compounds according to the present invention typically include such compounds in association with a pharmaceutically acceptable carrier.

[0141] The carrier(s) should be “acceptable” in the sense of being compatible with the other ingredients of the formulations and not deleterious to the recipient. Pharmaceutically acceptable carriers, in this regard, are intended to include any and all solvents, dispersion media, coatings, anti-bacterial and anti-fungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. The use of such media and agents for pharmaceutically active substances is known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds (identified or designed according to the invention and/or known in the art) also can be incorporated into the compositions. The formulations may conveniently be presented in dosage unit form and may be prepared by any of the methods well known in the art of pharmacy/microbiology. In general, some formulations are prepared by bringing the compound into association with a liquid carrier or a finely divided solid carrier or both, and then, if necessary, shaping the product into the desired formulation.

[0142] A pharmaceutical composition of the invention should be formulated to be compatible with its intended route of administration. Examples of routes of administration include oral or parenteral, for example, intravenous, intradermal, inhalation, transdermal (topical), transmucosal, and rectal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose. pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide.

[0143] Useful solutions for oral or parenteral administration can be prepared by any of the methods well known in the pharmaceutical art, described, for example, in Remington's Pharmaceutical Sciences, 18th ed. (Mack Publishing Company, 1990). Formulations for parenteral administration can also include glycocholate for buccal administration, methoxysalicylate for rectal administration, or citric acid for vaginal administration. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic. Suppositories for rectal administration also can be prepared by mixing the drug with a non-irritating excipient such as cocoa butter, other glycerides, or other compositions which are solid at room temperature and liquid at body temperatures. Formulations also can include, for example, polyalkylene glycols such as polyethylene glycol, oils of vegetable origin, and hydrogenated naphthalenes. Formulations for direct administration can include glycerol and other compositions of high viscosity. Other potentially useful parenteral carriers for these drugs include ethylene-vinyl acetate copolymer particles, osmotic pumps, implantable infusion systems, and liposomes. Formulations for inhalation administration can contain as excipients, for example, lactose, or can be aqueous solutions containing, for example, polyoxyethylene-9-lauryl ether, glycocholate and deoxycholate, or oily solutions for administration in the form of nasal drops, or as a gel to be applied intranasally. Retention enemas also can be used for rectal delivery.

[0144] Formulations of the present invention suitable for oral administration may be in the form of: discrete units such as capsules, gelatin capsules, sachets, tablets, troches, or lozenges, each containing a predetermined amount of the drug; a powder or granular composition; a solution or a suspension in an aqueous liquid or non-aqueous liquid; or an oil-in-water emulsion or a water-in-oil emulsion. The drug may also be administered in the form of a bolus, electuary or paste. A tablet may be made by compressing or molding the drug optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing, in a suitable machine, the drug in a free-flowing form such as a powder or granules, optionally mixed by a binder, lubricant, inert diluent, surface active or dispersing agent. Molded tablets may be made by molding, in a suitable machine, a mixture of the powdered drug and suitable carrier moistened with an inert liquid diluent.

[0145] Oral compositions generally include an inert diluent or an edible carrier. For the purpose of oral therapeutic administration, the active compound can be incorporated with excipients. Oral compositions prepared using a fluid carrier for use as a mouthwash include the compound in the fluid carrier and are applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose; a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.

[0146] Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor ELTM (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). It should be stable under the conditions of manufacture and storage and should be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyetheylene glycol), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as manitol, sorbitol, sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

[0147] Sterile injectable solutions can be prepared by incorporating the active compound in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filter sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle which contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, methods of preparation include vacuum drying and freeze-drying which yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

[0148] Formulations suitable for intra-articular administration may be in the form of a sterile aqueous preparation of the drug that may be in microcrystalline form, for example, in the form of an aqueous microcrystalline suspension. Liposomal formulations or biodegradable polymer systems may also be used to present the drug for both intra-articular and ophthalmic administration.

[0149] Formulations suitable for topical administration, including eye treatment, include liquid or semi-liquid preparations such as liniments, lotions, gels, applicants, oil-in-water or water-in-oil emulsions such as creams, ointments or pastes; or solutions or suspensions such as drops. Formulations for topical administration to the skin surface can be prepared by dispersing the drug with a dermatologically acceptable carrier such as a lotion, cream, ointment or soap. Particularly useful are carriers capable of forming a film or layer over the skin to localize application and inhibit removal. For topical administration to internal tissue surfaces, the agent can be dispersed in a liquid tissue adhesive or other substance known to enhance adsorption to a tissue surface. For example, hydroxypropylcellulose or fibrinogen/thrombin solutions can be used to advantage. Alternatively, tissue-coating solutions, such as pectin-containing formulations can be used.

[0150] For inhalation treatments, inhalation of powder (self-propelling or spray formulations) dispensed with a spray can, a nebulizer, or an atomizer can be used. Such formulations can be in the form of a fine powder for pulmonary administration from a powder inhalation device or self-propelling powder-dispensing formulations. In the case of self-propelling solution and spray formulations, the effect may be achieved either by choice of a valve having the desired spray characteristics (i.e., being capable of producing a spray having the desired particle size) or by incorporating the active ingredient as a suspended powder in controlled particle size. For administration by inhalation, the compounds also can be delivered in the form of an aerosol spray from pressured container or dispenser which contains a suitable propellant, e.g., a gas such as carbon dioxide, or a nebulizer.

[0151] Systemic administration also can be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants generally are known in the art, and include, for example, for transmucosal administration, detergents and bile salts. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds typically are formulated into ointments, salves, gels, or creams as generally known in the art.

[0152] The active compounds may be prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. Liposomal suspensions can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Pat. No. 4,522,811.

[0153] Oral or parenteral compositions can be formulated in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and the limitations inherent in the art of compounding such an active compound for the treatment of individuals. Furthermore, administration can be by periodic injections of a bolus, or can be made more continuous by intravenous, intramuscular or intraperitoneal administration from an external reservoir (e.g., an intravenous bag).

[0154] Where adhesion to a tissue surface is desired the composition can include the drug dispersed in a fibrinogen-thrombin composition or other bioadhesive. The compound then can be painted, sprayed or otherwise applied to the desired tissue surface. Alternatively, the drugs can be formulated for parenteral or oral administration to humans or other mammals, for example, in effective amounts, e.g., amounts that provide appropriate concentrations of the drug to target tissue for a time sufficient to induce the desired effect.

[0155] Where the active compound is to be used as part of a transplant procedure, it can be provided to the living tissue or organ to be transplanted prior to removal of tissue or organ from the donor. The compound can be provided to the donor host. Alternatively or, in addition, once removed from the donor, the organ or living tissue can be placed in a preservation solution containing the active compound. In all cases, the active compound can be administered directly to the desired tissue, as by injection to the tissue, or it can be provided systemically, either by oral or parenteral administration, using any of the methods and formulations described herein and/or known in the art. Where the drug comprises part of a tissue or organ preservation solution, any commercially available preservation solution can be used to advantage. For example, useful solutions known in the art include Collins solution, Wisconsin solution, Belzer solution, Eurocollins solution and lactated Ringer's solution.

[0156] Active compound as identified or designed by the methods described herein can be administered to individuals to treat disorders (prophylactically or therapeutically). In conjunction with such treatment, pharmacogenomics (i.e., the study of the relationship between an individual's genotype and that individual's response to a foreign compound or drug) may be considered. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drug. Thus, a physician or clinician may consider applying knowledge obtained in relevant pharmacogenomics studies in determining whether to administer a drug as well as tailoring the dosage and/or therapeutic regimen of treatment with the drug.

[0157] In therapeutic use for treating, or combating, bacterial infections in mammals, the compounds or pharmaceutical compositions thereof will be administered orally, parenterally and/or topically at a dosage to obtain and maintain a concentration, that is, an amount, or blood-level or tissue level of active component in the animal undergoing treatment which will be anti-microbially effective. The term “effective amount” is understood to mean that the compound of the invention is present in or on the recipient in an amount sufficient to elicit biological activity, for example, anti-microbial activity, anti-fungal activity, anti-viral activity, anti-parasitic activity, and/or anti-proliferative activity. Generally, an effective amount of dosage of active component will be in the range of from about 0.1 to about 100, more preferably from about 1.0 to about 50 mg/kg of body weight/day. The amount administered will also likely depend on such variables as the type and extent of disease or indication to be treated, the overall health status of the particular patient, the relative biological efficacy of the compound delivered, the formulation of the drug, the presence and types of excipients in the formulation, and the route of administration. Also, it is to be understood that the initial dosage administered may be increased beyond the above upper level in order to rapidly achieve the desired blood-level or tissue level, or the initial dosage may be smaller than the optimum and the daily dosage may be progressively increased during the course of treatment depending on the particular situation. If desired, the daily dose may also be divided into multiple doses for administration, for example, two to four times per day.

6. Examples

[0158] Exemplary compounds synthesized in accordance with the invention are listed in Table 2.

[0159]

TABLE 2
Compound
Number	Structure
1001
	N-{3-[2-Fluoro-4′-(2-[1,2,3]triazol-1-yl-ethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1002
	N-{3-[2-Fluoro-4′-(2-imidazol-1-yl-ethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1003
	2-(4-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-piperazin-1-yl)-acetamide
1004
	N-{3-[4′-(4-Cyanomethyl-piperazin-1-ylmethyl)-2-fluoro-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1005
	N-{3-[4′-(4-Cyanomethyl-piperazin-1-ylmethyl)-2,3′-difluoro-biphenyl-
	4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1006
	N-{3-[2-Fluoro-4′-(4-formyl-piperazin-1-ylmethyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1007
	N-{3-[2-Fluoro-4′-(1H-tetrazol-5-ylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1008
	N-[3-(2-Fluoro-4′-imidazol-1-ylmethyl-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
1009
	N-[3-(2,3′-Difluoro-4′-[1,2,3]triazol-1-ylmethyl-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
1010
	N-[3-(2,3′-Difluoro-4′-imidazol-1-ylmethyl-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
1011
	N-{3-[4′-Aminomethyl-[1,2,3]triazol-1-ylmethyl)-2-fluoro-biphenyl-
	4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1012
	N-{3-[2-Fluoro-4′-(4-methylaminomethyl-[1,2,3]triazol-1-ylmethyl)-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1013
	N-{3-[4′-(4-Dimethylaminomethyl-[1,2,3]triazol-1-ylmethyl)-2-fluoro-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1014
	N-(1-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-1H-[1,2,3]triazol-4-ylmethyl)-2-amino-acetamide
1015
	N-[3-(2-Fluoro-4′-[1,2,3]triazol-1-ylmethyl-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
1016
	N-{3-[2-(Fluoro-4′-(5-(S)-oxo-2,5-(S)-dihydro-[1,2,4]oxadiazol-3-
	ylmethyl)-biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1017
	N-{3-[2-Fluoro-4′-(5-(S)-methyl[1,2,4]oxadiazol-3-ylmethyl)-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1018
	N-{3-[2,6-Difluoro-4′-(4-hydroxymethyl-[1,2,3]triazol-1-ylmethyl)-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1019
	N-{3-[4′-(4-Dimethylaminomethyl-[1,2,3]triazol-1-ylmethyl)-2,6-
	difluoro-biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1020
	N-[3-(2-Fluoro-4′-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-thiazol-4-
	ylmethyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
1021
	N-(3-{2-Fluoro-4′-[2-(3-methoxyt-benzylamino)-thiazol-4-ylmethyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1022
	N-{3-[4′-(3-Cyano-azetidin-1-ylmethyl)-2-fluoro-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1023
	N-[3-(2-Fluoro-4′-[1,2,3]triazol-2-ylmethyl-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
1024
	N-{3-[4′-(5-Amino-tetrazol-2-ylmethyl)-2-fluoro-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1025
	N-{3-[4′-(5-Amino-tetrazol-1-ylmethyl)-2-fluoro-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1026
	1-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-5-amino-1H-[1,2,3]triazoe-4-carboxylic acid
	amide
1027
	N-{3-[2-Fluoro-4′-(7-oxo-6,7-dihydro-[1,2,3]triazolo[4,5-d]pyrimidin-
	3-ylmethyl)-biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-
	acetamide
1028
	N-{3-[2-Fluoro-4′-(4-hydroxymethyl-[1,2,3]triazol-1-ylmethyl)-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1029
	N-(3-{2-Fluoro-4′-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1030
	N-(3-{2-Fluoro-4′-[4-(2-hydroxy-ethyl)-piperidin-1-ylmethyl]-biphenyl-
	4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1031
	N-{3-[4′-(R)-(1-Amino-2-imidazol-1-yl-ethyl)-2-fluoro-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1032
	5-(S)-Aminomethyl-3-(2-fluoro-4′-tetrazol-1-ylmethyl-biphenyl-4-yl)-
	oxazolidin-2-one
1033
	2-Chloro-N-[3-(2-fluoro-4′-tetrazol-1-ylmethyl-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
1034
	2,2-Dichloro-N-[3-(2-fluoro-4′-tetrazol-1-ylmethyl-biphenyl-4-yl)-2-
	oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
1035
	N-{3-[3-Fluoro-4-(6-tetrazol-1-ylmethyl-pyridin-3-yl)-phenyl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1036
	N-{3-[3-Fluoro-4-(6-[1,2,3]triazol-1-ylmethyl-pyridin-3-yl)-phenyl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1037
	N-[3-(2-Fluoro-4′-[1,2,4]triazol-1-ylmethyl-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
1038
	N-(3-{4′-[4-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-piperazin-1-
	ylmethyl]-2-fluoro-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-
	acetamide
1039
	[{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-yl}-(2H-tetrazol-5-(R/S)-yl)-methyl]-carbamic acid benzyl
	ester
1040
	N-(3-{4′-[Amino-(2H-tetrazol-5-(R/S)-yl)-methyl]-2-fluoro-biphenyl-4-
	yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1041
	[{4′-[5-(S)-(Acetylamino-mjethyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-yl}-(2-methyl-2H-tetrazol-5-(R/S)-yl)-methyl]-carbamic
	acid benzyl ester
1042
	N-(3-{4′-[Amino-(2-methyl-2H-tetrazol-5-(R/S)-yl)-methyl]-2-fluoro-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1043
	N-[3-(2-Fluoro-4′-pyrazol-1-ylmethyl-biphenyl-4-yl)-2-oxo-oxazolidin-
	5-(S)-ylmethyl]-acetamide
1044
	N-(3-{2-Fluoro-4′-[2-(4-formyl-piperazin-1-yl)-1-(S)-hydroxy-ethyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1045
	N-(3-{2-Fluoro-4′-[1-(R)-(4-formyl-piperazin-1-yl)-2-hydroxy-ethyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1046
	N-{3-[2-Fluoro-4′-(1-(S)-hydroxy-2-imidazol-1-yl-ethyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1047
	N-[3-(2-Fluoro-4′-tetrazol-1-ylmethyl-biphenyl-4-yl)-2-oxo-oxazolidin-
	5-(S)-ylmethyl]-acetamide
1048
	N-[3-(2,6-Difluoro-4′-tetrazol-1-ylmethyl-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
1049
	1-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-1H-pyrazole-4-carboxylic acid ethyl ester
1050
	N-{3-[2-Fluoro-4′-(4-hydroxymethyl-imidazol-1-ylmethyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1051
	1-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-1H-pyrazol-4-carboxylic acid
1052
	N-{3-[2-Fluoro-4′-(4-methyl-pyrazol-1-ylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1053
	N-{3-[4′-(3-Amino-pyrazol-1-ylmethyl)-2-fluoro-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1054
	N-[3-(2-Fluoro-4′-pyrrol-1-ylmethyl-biphenyl-4-yl)-2-oxo-oxazolidin-5-
	(S)-ylmethyl]-acetamide
1055
	N-{3-[2-Fluoro-4′-(3-formyl-pyrrol-1-ylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1056
	N-[3-(2-Fluoro-4′-tetrazol-2-ylmethyl-biphenyl-4-yl)-2-oxo-oxazolidin-
	5-(S)-ylmethyl]-acetamide
1057
	3-{4-[5-(S)-(Acetylam,ino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphjenyl-4-ylmethyl}-5-amino-3H-imidazol-4-carboxylic acid amide
1058
	N-{3-[2-Fluoro-4′-(5-methyl-tetrazol-1-ylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1059
	N-{3-[2-Fluoro-4′-(5-methyl-tetrazol-2-ylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1060
	N-(3-{2-Fluoro-4′-[1-(R)-hydroxy-2-(1H-tetrazol-5-yl)-ethyl]-biphenyl-
	4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1061
	N-{3-[2-Fluoro-4′-(1-(S)-hydroxy-2-[1,2,3]triazol-1-yl-ethyl)-biphenyl-
	4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1062
	N-{3-[4′-(2-Azeidin-1-yl-1-(S)-hydroxy-ethyl)-2-fluoro-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1063
	N-{3-[4′-(1-(R)-Azetidin-1-yl-2-hydroxy-ethyl)-2-fluoro-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1064
	N-[3-(2-Fluoro-4′-thiomorpholin-4-ylmethyl-biphenyl-4-yl)-2-oxxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
1065
	N-{3-[2-Fluoro-4′-(1-oxo-1lambda*4*-thiomorpholin-4-ylmethyl)-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1066
	N-{3-[2-Fluoro-4′-(2-methyl-imidazol-1-ylmethyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1067
	N-{3-[2-Fluoro-4′-(5-methyl-imidazol-1-ylmethyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1068
	N-{3-[4′-(2,4-DImethyl-imidazol-1-ylmethyl)-2-fluoro-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1069
	N-{3-[4′-(3-Amino-[1,2,4]triazol-1-ylmethyl,)-2-fluoro-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1070
	N-[3-(2-Fluoro-4′-thiazolidin-3-ylmethyl-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
1071
	N-{3-[3-Fluoro-4-(6-pyrrol-1-ylmethyl-pyridin-3-yl)-phenyl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1072
	N-{3-[3-Fluoro-4-(6-[1,2,4]triazol-1-ylmethyl-pyridin-3-yl)-phenyl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1073
	N-{3-[2-Fluoro-4′-(2-hydroxy-1-(R)-[1,2,3]triazol-1-yl-ethyl)-biphenyl-
	4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1074
	N-(3-{4′-[1-(R)-(3,3-Difluoro-piperidin-1-yl)-2-hydroxy-ethyl]-2-
	fluoro-biphenyl-4-yl}-2-oxooxazolidin-5-(S)-ylmethyl)-acetamide
1075
	N-(3-{4′-[2-(3,3-Difluoro-piperidin-1-yl)-1-(S)-hydroxy-ethyl]-2-
	fluoro-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1076
	N-{3-[3-Fluoro-4-(6-pyrazol-1-ylmethyl-pyridin-3-yl)-phenyl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1077
	N-{3-[3-Fluoro-4-(6-imidazol-1-ylmethyl-pyridin-3-yl)-phenyl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1078
	N-{3-[2-Fluoro-4′-(2-methylsulfanyl-4,5-dihydro-imidazol-1-ylmethyl)-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1079
	N-{3-[2-Fluoro-4′-(5-methylsulfanyl-tetrazol-1-ylmethyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1080
	N-{3-[2-Fluoro-4′-(5-methylsulfanyl-tetrazol-2-ylmethyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1081
	N-{3-[4′-(5-Ethylsulfanyl-tetrazol-1-ylmethyl)-2-fluoro-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1082
	N-{3-[4′-(5-Ethylsulfanyl-tetrazol-2-ylmethyl)-2-fluoro-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1083
	N-{3-[4′-(5-Chloro-tetrazol-1-ylmethyl)-2-fluoro-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1084
	3-(2-Fluoro-4′-imidazol-1-ylmethyl-biphenyl-4-yl)-5-(R)-[1,2,3]triazol-
	1-ylmethyl-oxazolidin-2-one
1085
	3-(2-Fluoro-4′-pyrazol-1-ylmethyl-biphenyl-4-yl)-5-(R)-[1,2,3]triazol-1-
	ylmethyl-oxazolidin-2-one
1086
	N-{3-[2-Fluorro-4′-(1H-imidazol-4-ylmethyl)-biphenyl-4-yl]-2-oxxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1087
	N-{3-[2-Fluoro-4′-(3-(S)-hydroxy-pyrrolidin-1-ylmethyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1088
	N-{3-[2-Fluoro-4′(3-(R)-hydroxy-pyrrolidin-1-ylmethyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1089
	N-{3-[2,6-Difluoro-4′-(4-hydroxymethyl-[1,2,3]triazol-1-ylmethyl)-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1090
	N-[3-(4′-Azetidin-1-ylmethyl-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-
	5-(S)-ylmethyl]-acetamide
1091
	N-{3-[4′-(3-(R)-Amino-pyrrolidin-1-ylmethyl)-2-fluoro-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1092
	N-{3-[4′-(3-(S)-Amino-pyrrolidin-1-ylmethyl)-2-fluoro-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1093
	1-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-pyrrolidine-3-(R/S)-carboxylic acid amide
1094
	N-{3-[2-Fluoro-4′-(4-fluoro-piperidin-1-ylmethyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1095
	N-{3-[2-Fluoro-4′-(5-fluoromethyl-2-oxo-oxazolidin-3-(R/S)ylmethyl)-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1096
	N-{3-[2-Fluoro-4′-(3-(R/S)-fluoro-piperidin-1-ylmethyl)-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1097
	N-{3-[4′-(3,3-Difluoro-piperidin-1-ylmethyl)-2-fluoro-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1098
	N-(3-{2-Fluoro-4′-[6-(3-fluoro-propylamino)-purtin-9-ylmethyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1099
	N-(3-{2-Fluoro-4′-[6-(2-hydroxy-ethylamino)-purin-9-ylmethyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1100
	N-{3-[4′-(6-Chloro-purin-9-ylmethbyl)-2-fluoro-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1101
	N-{3-[2-Fluoro-4′-(2-oxo-oxazolidin-3-ylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1102
	N-(3-{2-Fluoro-4′-[6-(2-fluoro-ethylamino)-purin-9-ylmethyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1103
	N-(3-{4′-[6-(2,2-Difluoro-ethylamino)-purin-9-ylmethyl]-2-fluoro-
	biphenyl-4-yl}-2-oxxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1104
	N-(3-{2-Fluoro-4′-[6-(2,2,2-trifluoro-ethylamino)-purin-9-ylmethyl]-
	biphenyl-4-yl}-2-oxxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1105
	N-{3-[4′-(6-Dimethylamino-purin-9-ylmethyl)-2-fluoro-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1106
	N-{3-[2-0Fluoro-4′-(6-methylamino-purin-9-ylmethyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1107
	N-(3-{2-Fluoro-4′-[6-(3-hydroxy-propylamino)-purin-9-ylmethyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1108
	N-(3-{2-Fluoro-4′-[6-(2-methylsulfanyl-ethylamino)-purin-9-ylmethyl-
	biphjenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1109
	N-(3-{2-Fluoro-4′-[6-(4-hydroxy-butylamino)-purin-9-ylmethyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
1110
	N-{3-[4′-(6-Amino-purin-9-ylmethyl)-2-fluoro-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1111
	N-{3-[2-Fluoro-4′-(6-oxo-1,6-dihydro-purin-9-ylmethyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1112
	N-[3-(2-Fluoro-4′-isoxazolidin-2-ylmethyl-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
1113
	N-{3-[4′-(2-Amino-imidazol-1-ylmethyl)-2-fluoro-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1114
	N-{3-[2-Fluoro-4′-(7-oxo-4,5-dihydro-[1,2,3]triazolo[1,5-c]pyrimidin-6-
	ylmethyl)-biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1115
	N-[3-(2-Fluoro-4′-pyrrolidin-1-ylmethyl-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
1116
	N-[3-(2-Fluorro-4′-piperidin-1-ylmethyl-bniphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
1117
	N-{3-[2-Fluoro-4′-(1-(S)-hydroxy-2-morpholin-4-yl-ethyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1118
	N-{3-[2-Fluoro-4′-(2-hydroxy-1-(R)-morpholin-4-yl-ethyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1119
	(1-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-pyrrolidin-3-(R)-yl)-carbamic acid tert-butyl ester
1120
	(1-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-pyrrolidin-3-(S)-yl)-carbamic acid tert-butyl ester
1121
	1-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-piperidine-3-(R/S)-carboxylic acid amide
1122
	1-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-pyrrolidine-2-(S)-carboxylic acid amide
1123
	N-{3-[2-Fluoro-4′-(3-oxo-piperazin-1-ylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1124
	N-{3-[4′-(2,2-Dimethyl-4-oxo-imidazolidin-1-ylmethyl)-2-fluoro-
	biphenyl-4-yl]-2-oxxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1125
	1-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-azetidine-3-(R/S)-carboxylic acid amide
1126
	1-{4′-[5-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-azetidine-2-carboxylic acid amide
1127
	N-{3-[2-Fluoro-4′-(2-oxo-piperazin-1-ylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
1128
	2-(4-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-3-oxo-piperazin-1-yl)-acetamide
1129
	N-{3-[4′-(4-Cyanomethyl-2-oxo-piperazin-1-ylmethyl)-2-fluoro-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
1130
	N-{3-[2-Fluoro-4′-(2-oxo-4-[1,2,3]thiazdiazol-4-ylmethyl-piperazin-1-
	ylmethyl)-biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2001
	N-{3-[2-Fluoro-4′-(5-methyl-isoxazol-4-yloxymethyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2002
	N-{3-[2-Fluoro-4′-([1,2,4]triazol-4-ylamino0methyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2003
	N-(3-{2-Fluoro-4′-[(3-methyl-isoxazol-5-ylamin)-methyl-biphenyl-4-
	yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2004
	N-(3-{2-Fluorro-4′-[(5-methyl-isoxazol-3-ylamino)-methyl]-biphenyl-4-
	yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2005
	4-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-amino)-piperidine-1-carboxylic acid ethyl ester
2006
	N-(3-{4′-[(1-Aza-bicyclo[2.2.2]oct-3-ylamino)-methyl]-2-fluoro-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2007
	2-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-amino)-benzamide
2008
	2-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-amino)-thiophene-3-carboxylic acid amide
2009
	N-(3-{2-Fluoro-4′-[(3-oxo-isoxazolidin-4-(R)-ylamino)-methyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2010
	N-(3-{2-Fluoro-4′-[(3-oxo-isoxazolidin-4-(S)-ylamino)_-methyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2011
	N-{3-[4′-(Azetidin-3-(R/S)-ylaminomethyl)-2-fluoro-biuphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2012
	N-(3-{4′-[(3-Aminomethyl-[1,2,4]thiadiazol-5-ylamino)-methyl]-2-
	fluoro-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2013
	N-[5-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-
	fluoro-biphenyl-4-ylmethyl}-amino)-[1,2,4]thiadiazol-3-ylmethyl]-2-
	(S)-amino-propionamide
2014
	2,6-Diamino-hexanoic acid [5-({4′-[5-(acetylamino-methyl)-2-oxo-
	oxazolidin-3-yl]-2′-fluoro-nbiphenyl-4-ylmethyl}-amino)-
	[1,2,4]thiadiazol-3-ylmethyl]-amide
2015
	N-{3-[2-Fluoro-4′-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-biphenyl-
	4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2016
	N-{3-[2-Fluoro-4′-(3H-[1,2,3]triazol-4-ylsulfanylmethyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2017
	N-{3-[4′-(4,6-Dioxo-1,4,5,6-tetrahydro-pyrimidin-2-ylsulfanylmethyl)-
	2-fluoro-biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2018
	N-{3-[2-Fluoro-4′-(pyridin-2-ylsulfanylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
2019
	N-{3-[2-Fluoro-4′-(pyridin-4-ylsulfanylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
2020
	N-{3-[2-Fluoro-4′-(1-methyl-1H-tetrazole-5-sulfinylmethyl)-biphenyl-
	4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2021
	N-{3-[2-Fluoro-4′-(3H-[1,2,3]triazol-4-sulfinylmethyl)-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2022
	N-{3-[2-Fluoro-4′-(pyridine-4-sulfinylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
2023
	N-{3-[2-Fluoro-4′-(pyridine-2-sulfinylmethyl)-biphenyl-4-yl]-2-oxo-
	oxaolidin-5-(S)-ylmethyl}-acetamide
2024
	N-{3-[2-Fluoro-4′-(1-methyl-1H-tetrazole-5-sulfonylmethyl)-biphenyl-
	4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2025
	N-{3-[2-Fluoro-4′-(3H-[1,2,3]triazole-4-sulfonylmethyl)-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2026
	N-(3-{2-Fluoro-4′-[2-(3H-[1,2,3]triazol-4-ylsulfanyl)-ethyl]-biphenyl-4-
	yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2027
	N-(3-{4′-[1-(2-Dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-
	2-fluoro-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl-acetamide
2028
	N-{3-[4′-(5-Amino-4H-[1,2,4]triazool-3-ylsulfanylmethyl)-2-fluoro-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2029
	N-{3-[2-Fluoro-4′-([1,3,4]thiazidazol-2-ylsulfanylmethyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2030
	N-{3-[2-Fluoro-4′-(thiazol-2-ylsulfanylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
2031
	N-{3-[2-Fluoro-4′-(4-methyl-thiazol-2-ylsulfanylmethyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2032
	N-{3-[2-Fluoro-4′-(1H-imidazol-2-ylsulfanylmethyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2033
	N-{3-[2-Fluorro-4′-(2-methyl-2H-[1,2,4]triazol-3-ylsulfanylmethyl)-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2034
	N-{3-[2-Fluoro-4′-(2-methyl-2H-[1,2,4]triazol-3-ylsulfanylmethyl)-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2035
	N-{3-[2-Fluoro-4′-([1,3,4]-thiadiazole-2-sulfinylmethyl)-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2036
	N-{3-[2-Fluoro-4′-(thiazole-2-sulfinylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
2037
	N-{3-[2-Fluoro-4′-(4-methyl-thiazole-2-sulfinylmethyl)-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2038
	N-{3-[2-Fluoro-4′-(1H-imidazole-2-sulfinylmethyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2039
	N-{3-[2-Fluoro-4′-(2-methyl-2H-[1,2,4]triazole-3-sulfinylmethyl)-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2040
	N-(3-{3-Fluoro-4-[6-(3H-[1,2,3]triazol-4-ylsulfanylmethyl)-pyridin-3-
	yl]-phenyl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2041
	N-{3-[2-Fluoro-4′-(pyridin-2-yl-hydrazonomethyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2042
	N-(3-{2-Fluoro-4′-[(4-trifvluoromethyl-pyrimidin-2-yl)-
	hydrazonomethyl]-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-
	acetamide
2043
	N-(3-{2-Fluoro-4′-[(1-methyl-1H-imidazole-4-sulfonylamino)-methyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2044
	N-(3-{2-Fluoro-4′-[(6-morpholin-4-yl-pyridine-3-sulfonylamino)-
	methyl]-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2045
	N-{3-[2-Fluoro-4′-(pyridin-3-ylsulfamoylmethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-05-(S)-ylmethyl}-acetamide
2046
	N-{3-[2-Fluoro-4′-([1,2,4]triazol-4-ylaminomethyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2047
	N-{3-[2-Fluoro-4′-(2H-[1,2,4]triazol-3-ylsulfanylmethyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2048
	N-{3-[2-Fluoro-4′-(N′-pyridin-2-yl-hydrazinomethyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
2049
	N-(3-{4′-[N′-(4,5-Dihydro-1H-imidazol-2-yl)-hydrazinomethyl]-2-
	fluoro-biphenyl-4-yl}-2-oxo-oxazoliddin-5-(S)-ylmethyl)-acetamide
2050
	N-{3-[2-Fluoro-4′-(isoxazol-3-ylaminomethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
2051
	N-(3-{2-Fluoro-4′-[(quinoline-8-sulfonylamino)-methyl]-biphenyl-4-
	yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2052
	N-(3-{2-Fluoro-4′-[(1-methyl-1H-imidazole-4-sulfonylzamino)-methyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2053
	N-(3-{2-Fluoro-4′-[(6-morpholin-4-yl-pyridine-3-sulfonylamino)-
	methyl]-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2054
	N-{3-[2-Fluoro-4′-pyridin-3-ylsulfamoylmethyl)-biphenyl-4-yl]2-oxo-
	oxazolidin-5-(S)-ylmethyl}acetamide
2055
	5-({4′-[5-(S)-(Acetylamino-methyl)-2-oxxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-amino)-3H-imidazole-4-carboxylic acid amide
2056
	N-{3-[2-Fluoro-4′-(morpholin-4-ylaminomethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
2057
	N-(3-{2-Fluoro-4′-[(4-methyl-piperazin-1-ylamino)-methyl]-biphenyl-4-
	yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2058
	N-(3-{2-Fluoro-4′-[(4-trifluoromethyl-benzenesulfonylamino)-methyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
2059
	N-(3-{2-Fluoro-4′-[(2-oxo-piperidin-3-(S)-ylamino)-methyl]-biphenyl-
	4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
3001
	N-{3-[2-Fluoro-4′-(pyridin-4-ylmethylsulfanyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
3002
	N-{3-[2-Fluoro-4′-(pyridin-4-ylmethylsulfinyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
3003
	N-{3-[2-Fluoro-4′-pyridin-4-ylmethanesulfonyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
3004
	N-{3-[2-Fluoro-4′-(1-oxy-pyridin-4-ylmethanesulfonyl)-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
3005
	N-(3-{2-Fluoro-4′-[(pyridin-4-ylmethyl)-sulfamoyl]-biphenyl-4-yl}-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
3006
	N-(3-{2-Fluoro-4′-[(pyridin-2-ylmethyl)-sulfamoyl]-biphenyl-4-yl}-2-
	oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
3007
	N-{3-[2-Fluoro-4′-(2-pyridin-2-yl-ethylsulfamoyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4001
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-3-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-
	pyrimidin-5-yl)-acrylamide
4002
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-3-pyridin-3-yl-acrylamide
4003
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-3-(2,4-dimethoxy-6-methyl-pyrimidin-5-yl)-
	acrylamide
4004
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-3-(4-hydroxy-2-methoxy-6-methyl-pyrimidin-5-
	yl)-acrylamide
4005
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-3-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-
	pyrimidin-5-yl)-acrylamide
4006
	N-{4′[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-3-pyrimidin-5-yl-acrylamide
4007
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-3-(1-methyl-6-oxo-1,6-dihydro-pyrimidin-5-yl)-
	acrylamide
4008
	Quinoline-4-carboxylic acid {4′-[5-(S)-(acetylamino-methyl)-2-oxo-
	oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4009
	Quinoline-3-carboxylic acid {4′-[5-(S)-(acetylamino-methyl)-2-oxo-
	oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4010
	1-Methyl-1H-pyrrole-2-carboxylic acid {4′-[5-(S)-(acetylamino-
	methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4011
	1H-Imdole-6-carboxylic acid {4′-[5-(S)-(acetylamino-methyl)-2-oxxo-
	oxazolidin-03-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4012
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-3-methanesulfonyl-benzamide
4013
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphjenyl-4-ylmethyl}-4-fluoro-benzamide
4014
	Benzo[1,3]dioxole-5-carboxylic acid {4′-[5-(S)-(acetylamino-methyl)-2-
	oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4015
	5-Methoxy-1H-indole-2-carboxylic acid {4′-[5-(S)-(acetylamino-
	methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4016
	N-[3-(2-Fluoro-4′-{[(quinolin-4-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-
	acetamide
4017
	N-(3-{2-Fluoro-4′-[(4-pyridin-2-yl-benzylamino)-methyl]-biphenyl-4-
	yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4018
	N-[3-(2-Fluoro-4′-{[(pyridin-4-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4019
	N-[3-(2-Fluoro-4′-{[(quinolin-2-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4020
	N-[3-(4′-{[(Benzofuran-2-ylmethyl)-amino]-methyl}-2-fluoro-biphenyl-
	4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4021
	N-[3-(2-Fluoro-4′-{[(quinolin-3-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4022
	N-[3-(2-Fluoro-4′-{[(naphthalen-1-ylmethyl)-amino]-methyl}-biphenyl-
	4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4023
	N-[3-(2-Fluoro-4′-{[(furan-3-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-
	2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4024
	N-[3-(2-Fluoro-4′-{[(pyridin-2-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4025
	N-[3-(2-Fluoro-4′-{[(pyridin-3-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4026
	N-[3-(2-Fluoro-4′-{[(furan-2-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-
	2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4027
	N-[3-(2-Fluoro-2′-methoxy-4′-{[(pyridin-4-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4028
	N-[3-(2-Fluoro-4′-{[(furan-3-ylmethyl)-amino]-methyl}-2′-methoxy-
	biphenylk-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4029
	N-[3-(2-Fluoro-4′-{2-hydroxy-1-(R)[(pyridin-4-ylmethyl)-amino]-
	ethyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4030
	N-[3-(4′-{1-(R)-[(2,4-Dihydroxy-6-methyl-pyrimidin-5-ylmethyl)-
	amino]-2-hydroxy-ethyl}-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-
	(S)-ylmethyl]-acetamide
4031
	N-[3-(2-Fluoro-4′-{2-hydroxy-1-(R)-[(quinolin-4-ylmethyl)-amino]-
	ethyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4032
	N-(3-{2-Fluoro-4′-[(methyl-quinolin-4-ylmethyl-amino)-methyl]-
	biphenyl-4-yl}-2-oxo-oxaolidin-5-(S)-ylmethyl)-
	acetamide
4033
	N-(3-{2-Fluoro-2′-methoxy-4′-[(methyl-pyridin-4-ylmethyl-amino)-
	methyl]-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4034
	N-(3-{2-Fluoro-4′-[(furan-3-ylmethyl-methyl-amino)-methyl]-2′-
	methoxy-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4035
	N-(3-{4′-[(Ethyl-pyridin-4-ylmethyl-amino)-methyl]-2-fluoro-biphenyl-
	4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4036
	N-[3-(4′-{[(2,4-Dihydroxy-6-methyl-pyrimidin-5-ylmethyl)-methyl-
	amino]-methyl}-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-
	ylmethyl]-acetamide
4037
	N-[3-(4′-{[Bis-(4-hydroxy-3-methoxy-benzyl)-amino]-methyl}-2-
	fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4038
	N-[3-(2-Fluoro-4′-{[(isoxazol-4-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4039
	N-(3-{2-Fluoro-2′-methoxy-4′-[(methyl-pyridin-4-ylmethyl-amino)-
	methyl]-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl-acetamide
4040
	N-[3-(2-Fluoro-2′-methoxy-4′-{[(pyridin-4-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4041
	N-(3-{2-Fluoro-2′-methoxy-4′-[(methyl-pyridin-4-ylmethyl-amino)-
	methyl]-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4042
	N-[3-(2-Fluoro-4′-{[furan-3-ylmethyl)-amino]-methyl}-2′-methoxy-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4043
	N-(3-{2-Fluoro-4′-[(furan-3-ylmethyl-methyl-amino)-methyl]-2′-
	methoxy-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4044
	N-(3-{2-Fluoro-4′-[(methyl-pyridin-4-ylmethyl-amino)-methyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4045
	N-(3-{2-Fluoro-4′-[(methyl-pyridin-2-ylmethyl-amino)-methyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4046
	N-[3-(4′-{[(3,5-Dichloro-benzyl)-methyl-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4047
	N-(3-{2-Fluoro-4′-[(methyl-pyridin-3-ylmethyl-amino)-methyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4048
	N-[3-(2-Fluoro-4′-{[(1H-pyrrol-2-ylmethyl)-amino]-methyl}-biphenyl-
	4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4049
	N-[3-(2-Fluoro-4′-{[(1-methyl-1H-indol-2-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4050
	1H-Indole-6-carboxylic acid {4′-[5-(S)-(acetylamino-methyl)-2-oxo-
	oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-methyl-amide
4051
	1-Methyl-1H-pyrrole-2-carboxylic acid {4′-[5-(S)-(acetylamino-
	methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-methyl-
	amide
4052
	N-{3-[3-Fluoro-4-(5-{[(pyridin-4-ylmethyl)-aamino]-methyl}-pyridin-2-
	yl)-phenyl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4053
	N-{3-[3-Fluoro-4-(5-{[(furan-3-ylmethyl)-amino]-methyl}-pyridin-2-
	yl)-phenyl]-2-ox-oxazolidin-5-(S)-ylmethyl}-acetamide
4054
	N-[3-(2-Fluoro-4′-{[(6-methoxy-pyridin-3-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4055
	N-[3-(2-Fluoro-4′-{[(6-methoxy-pyridin-3-ylmethyl)-methyl-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4056
	N-(3-{4′-[(2,5-Bis-trifluoromethyl-benzylamino)-methyl]-2-fluoro-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4057
	N-[3-(2-Fluoro-4′-{[(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-
	5-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-
	ylmethyl]-acetamide
4058
	N-[3-(2-Fluoro-4′-{[(furan-3-ylmethyl)-amino]-methyl}-2′-methoxy-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4059
	N-[3-(2-Fluoro-4′-{[(1-methyl-1H-pyrrol-2-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4060
	N-[3-(2-Fluoro-4′-{[(isoquinolin-4-ylmethyl)-amino]-methyl}-biphenyl-
	4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4061
	N-(3-{2-Fluoro-4′-[(furan-3-ylmethyl-methyl-amino)-methyl]-biphenyl-
	4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4062
	N-(3-{4′-[(4-Dimethylamino-benzylamino)-methyl]-2-fluoro-biphenyl-
	4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4063
	N-(3-{4′-[(4-Chloro-benzylamino)-methyl]-2-fluoro-biphenyl-4-yl}-2-
	oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4064
	N-(3-{4′-[(2,4-Dichloro-benzylamino)-methyl]-2-fluoro-biphenyl-4-yl}-
	2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4065
	N-[3-(2-Fluoro-4′-{[(isoquinolin-5-ylmethyl)-amino]-methyl}-biphenyl-
	4-yl)-2-oxo-oxazllidin-5-(S)-ylmethyl]-acetamide
4066
	N-[3-(2-Fluoro-4′-{[(3H-imidazol-4-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4067
	N-[3-(2-Fluoro-4′-{[(3H-imidazol-4-ylmethyl)-methyl-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4068
	N-[3-(2-Fluoro-4′-{[(1H-imidazol-4-ylmethyl)-(3H-imidazol-4-
	ylmethyl)-amino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-
	ylmethyl]-acetamide
4069
	N-[3-(2-Fluoro-4′-{[(5-nitro-furan-2-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4070
	N-(3-{4′-[(3-Cyano-benzylamino)-methyl]-2-fluoro-biphenyl-4-yl}-2-
	oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4071
	N-[3-(2-Fluoro-4′-{[(quinolin-6-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4072
	N-[3-(2-Fluoro-4′-{[(6-methyl-pyridin-2-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4073
	N-{3-[3-Fluoro-4-(6-{[(pyridin-4-ylmethyl)-amino]-methyl}-pyridin-3-
	yl)-phenyl-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4074
	N-[3-(2-Fluoro-4′-{[(thiazol-2-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4075
	N-[3-(2-Fluoro-4′-{[(5-hydroxymethyl-furan-2-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4076
	N-[3-(2-Fluoro-4′-{[(1-methyl-1H-imidaol-2-ylmethyl)-amino]-
	methyl)-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4077
	N-[3-(4′-{[(Benzo[b]thiophen-3-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4078
	N-[3-(4′-{[(5-Bromo-furan-2-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazoliddin-5-(S)-ylmethyl]-acetamide
4079
	N-(3-{2-Fluoro-4′-[(3-imidazol-1-yl-propylamino)-methyl]-biphenyl-4-
	yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4080
	N-{3-[2-Fluoro-4′-(N-pyridin-4-ylmethyl-carbamimidoyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4081
	N-[3-(2-Fluoro-4′-{[(5-methyl-furan-2-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4082
	N-[3-(2-Fluoro-4′-{[(5-methyl-3H-imidazol-4-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4083
	N-[3-(2-Fluoro-4′-{[(1H-indol-3-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4084
	N-[3-(2-Fluoro-4′-{[(5-phenyl-thiophen-2-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4085
	N-[3-(4′-{[(4,5-Dimethyl-furan-2-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4086
	N-[3-(2-Fluoro-4′-{[(thiophen-3-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4087
	N-(3-{2-Fluoro-4′-[(2-pyridin-2-yl-ethylamino)-methyl]-biphenyl-4-yl}-
	2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4088
	N-[2-Oxo-3-(2,2′,3′-trifluoro-4′-{[(furan-2-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)oxazolidin-5-(S)-ylmethyl]-acetamide
4089
	N-[2-Oxo-3-(2,2′,3′-trifluoro-4′-{[(pyridin-4-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-oxazolidin-5-(S)-ylmethyl]-acetamide3
4090
	N-[-Oxo-3-(2,2′,3′-trifluoro-4′-{[(pyridin-2-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-oxazolidin-5-(S)-ylmethyyl]-acetamide
4091
	N-[3-(2-Fluoro-4′-{[(1H-imidazol-2-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4092
	N-[3-(4′-{[(1H-Benzoimidazol-2-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4093
	N-(3-{2-Fluoro-4′-[(4-sulfamoyl-benzylamino)-methyl]-biphenyl-4-yl}-
	2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4094
	N-[3-(2-Fluoro-4′-{[2-(4-sulfamoyl-phenyl)-ethylamino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4095
	N-[3-(2-Fluoro-4′-{[(3-hydroxy-5-hydroxymethyl-2-methyl-pyridin-4-
	ylmethyl)-amino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-
	ylmethyl]-acetamide
4096
	N-[3-(2-Fluoro-4′-{[2-(4-methyl-thiazol-5-yl)-ethylamino]-methyyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4097
	N-{3-[2-Fluoro-4′-(N-pyridin-2-ylmethyl-carbamimidoyl)-biphenyl-4-
	yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4098
	N-[3-(2-Fluoro-4′-{[(5-methoxy-1H-indol-3-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4099
	N-[3-(2-Fluoro-4′-{[(3-methyl-thiophen-2-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4100
	N-[3-(4′-{[(1-Benzenesulfonyl-1H-pyrrol-2-ylmethyl)-amino]-methyl}-
	2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4101
	N-[3-(4′-{[(2,4-Dioxo-1,2,3,4-tetrahydro-pyrimidin-5-ylmethyl)-
	amino]-methyl}-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-
	ylmethyl]-acetamide
4102
	4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-carboxylic acid (pyridin-4-ylmethyl)-amide
4103
	N-[3-(4′-{[(2,5-Dimethyl-furan-3-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4104
	N-[3-(2-Fluoro-4′-{[(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4105
	N-[3-(2-Fluoro-4′-{[(5-methyl-2-trifluoromethyl-furan-3-ylmethyl)-
	amino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-
	acetamide
4106
	N-{4′-[5-(R)-(Acetylamino-methyl)-4,5-dihydro-isoxazol-3-yl]-
	biphenyl-4-ylmethyl}-phthalamic acid
4107
	N-(4-{5-[5-(R)-(Acetylamino-methyl)-4,5-(S)-dihydro-isoxazol-3-yl]-
	pyridin-2-yl}-benzyl)-phthalamic acid
4108
	N-[3-(4′-{[(2,4-Dimethyl-thiazol-5-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4109
	N-[3-(4′-{[(3,5-Dimethyl-isoxazol-4-ylmethyl)-amino]-methyl}-2-
	fluoro-biphenyl-4-yl)-2-oxo-oxazoloidin-5-(S)-ylmethyl]-acetamide
4110
	4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-carboxylic acid (pyridin-2-ylmethyl)-amide
4111
	4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-carboxylic acid (furan-2-ylmethyl)-amide
4112
	4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-carboxylic acid [2-(4-methyl-thiazol-5-yl)-ethyl]-amide
4113
	N-[3-(2-Fluoro-4′-{[(2-thiophen-2-yl-thiazol-4-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4114
	N-[3-(2-Fluoro-4′-{[(2-(2-oxo-imidazolidin-1-yl)-ethylamino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4115
	4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-carboxylic acid (2-pyridin-2-yl-ethyl)-amide
4116
	4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-carboxylic acid [2-(3H-imidazol-4-yl)-ethyl]-amide
4117
	N-[3-(2-Fluoro-4′-{[(2-morpholin-4-yl-pyridin-3-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4118
	N-[3-(2-Fluorro-4′-{[(6-morpholin-4-yl-pyridin-3-ylmethyl)-amino]-
	methyl}-biphjenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4119
	N-[3-(2-Fluoro-4′-{[(5-pyridin-2-yl-thiophen-2-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4120
	5-[({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-amino)-methyl]-2-methyl-furan-3-carboxylic acid
	methyl ester
4121
	N-[3-(4′-{[(Benzothiazol-2-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4122
	N-[3-(2-Fluoro-4′-{[(2-phenyl-thiazol-4-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4123
	N-[3-(2-Fluoro-4′-{[(2-phenyl-1H-imidazol-4-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ymethyl]-acetamide
4124
	N-[3-(4′-{[(2-Ethyl-3H-imidazol-4-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4125
	N-[3-(4′-{[(5-Chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-
	ylmethyl)-amino]-methyl}-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-
	(S)-ylmethyl]-acetamide
4126
	N-[3-(4′-{[(5-Chloro-1,3-dimethyl-1H-pyrazol-4-ylmethyl)-amino]-
	methyl}-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-
	acetamide
4127
	N-[3-(2-Fluoro-4′-{[(3-thiophen-2-yl-1H-pyrazol-4-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4128
	N-[3-(4′-{[(5-Cyano-6-methylsulfanyl-pyridin-2-ylomethyl)-amino]-
	methyl}-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-
	acetamide
4129
	N-[3-(4′-{[(2-Amino-4-oxo-4H-chromen-3-ylmethyl)-amino]-methyl}-
	2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4130
	N-[3-(2-Fluoro-4′-{[(2-methyl-5-phenyl-furan-3-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4131
	N-[3-(4′-{[(3,4-Dihydro-2H-pyran-2-ylmethyl)-amino]-methyl}-2-
	fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4132
	N-[3-(4′-{[(Pyridin-4-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-4,5-
	dihydro-isoxazol-5-(R)-ylmethyl]-acetamide
4133
	N-{3-[6-(4-{[(Pyridin-4-ylmethyl)-amino]-methyl}-phenyl)-pyridin-3-
	yl]-4,5-dihydro-isoxazol-5-(R)-ylmethyl}-acetamide
4134
	N-{2-Oxo-3-[6-(4-{[(pyridin-4-ylmethyl)-amino]-methyl}-phenyl)-
	pyridin-3-yl]-oxazolidin-5-(S)-ylmethyl}-acetamide
4135
	N-[3-(4′-{[(4-Amino-pyridin-3-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4136
	N-[3-(4′-{[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-
	ethanesulfonylamino]-methyl}-2-fluoro-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
4137
	N-[3-(2-Fluoro-4′-{[(thiuophen-2-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4138
	N-[3-(2-Fluoro-4′-{[(quinolin-7-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4139
	N-[3-(4′-{[(4-Chloro-1-methyl-1H-pyrazol-3-ylmethyl)-amino]-
	methyl}-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-
	acetamide
4140
	N-[3-(2-Fluoro-4′-{[(3-methyl-[1,2,4]oxadiazol-5-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4141
	N-[3-(2-Fluoro-4′-{[(5-methyl-[1,2,4]oxadiazol-3-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4142
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-isonicotinamide
4143
	4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-carboxylic acid (thiazol-2-ylmethyl)-amide
4144
	N-[3-(2-Fluoro-4′-{1-(R/S)-[(furan-3-ylmethyl)-amino]-ethyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4145
	N-[3-(2-Fluoro-4′-{1-(R/S)-[(thiazol-2-ylmethyl)-amino]-ethyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4146
	N-[3-(2-Fluoro-4′-{[(5-methyl-2-phenylk-2H-[1,2,3]triazol-4-ylmethyl)-
	amino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-
	acetamide
4147
	N-(3-{2-Fluoro-4′-[(4-pyrrol-1-yl-benzamino)-methyl]-biphenyl-4-
	yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4148
	N-[3-(2-Fluoro-4′-{[3-(5-methyl-1H-pyrazol-4-yl)-propylamino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4149
	N-[3-(2-Fluoro-4′-{2-[(pyridin-4-ylmethyl-amino]-ethyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4150
	N-[3-(2-Fluoro-4′-{[2-(R/S)-(1-methyl-pyrrolidin-2-yl)-ethylamino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4151
	N-[3-(2-Fluoro-4′-{[(2-methoxy-pyridin-3-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4152
	N-[3-(4′-{[(2-Amino-pyridin-3-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4153
	N-[3-(2-Fluoro-4′-{[(pyrrolidin-3-(R/S)-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4154
	N-[3-(2,3′-DFifluoro-4′-{[(thiazol-2-ylmethyl)-amino]-methyl}-biphenyl-
	4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4155
	N-[3-(2,3′-Difluoro-4′-{[(pyridin-4-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4156
	N-[3-(2-Fluoro-4′-{[3-(2-oxxo-pyrrolidin-1-yl)-propylamino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4157
	4-[({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-amino)-methyl]-1-cyclopropyl-2,5-dimethyl-1H-
	pyrrole-3-carboxylic acid ethyl ester
4158
	N-{3-[2-Fluoro-4′-({[5-(3-sulfamoyl-phenyl)-furan-2-ylmethyl]-
	amino}-methyl)-biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-
	acetamide
4159
	N-(3-{2-Fluoro-4′-[(1-pyridin-4-(R/S)-yl-ethylamino)-methyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4160
	N-(3-{2-Fluoro-4′-[1-(R/S)-(1-pyridin-4-(R/S)-yl-ethylamino)-ethyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4161
	N-[3-(4′-{[(5-Ethyl-furan-2-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4162
	N-[3-(4′-{[(5-Ethyl-thiophen-2-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4163
	N-[3-(2-Fluoro-4′-{[(1,3,5-trimethyl-1H-pyrazol-4-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4164
	N-[3-(2,3′-Difluoro-4′{[([1,2,3]thiadiazol-4-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4165
	N-[3-(2-Fluoro-4′-{[(2-methyl-1H-imidazol-4-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4166
	N-[3-(2-Fluoro-3′-{[([1,2,3]thiadiazol-4-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4167
	N-[3-(2-Fluoro-4′-{[(5-methylsulfanyl-thiophen-2-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4168
	N-[3-(4′-{[(4-Bromo-1-methyl1-H-pyrazol-3-ylmethyl)-amino]-
	methyl}-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-
	acetamide
4169
	N-[3-(4′-{[(4-Bromo-2H-pyrazol-3-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4170
	N-{3-[4′-(Benzylsulfamoyl-methyl)-2-fluorro-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
4171
	N-[3-(2-Fluoro-4′-{2-hydroxy-1-[([1,2,3]thiadiazol-4-(R/S)-ylmethyl)-
	amino]-ethyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-
	acetamide
4172
	N-[3-(2-Fluoro-4′-{2-hydroxy-1-[([1,2,3]thiadiazol-4-(R/S)-ylmethyl)-
	amino]-ethyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-
	acetamide
4173
	4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-carboxylic acid [1-carbamoyl-2-(S)-(3H-imidazol-4-yl)-
	ethyl]-amide
4174
	2-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-amino)-3-(S)-(1H-imidazol-4-yl)-propionamide
4175
	2-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-amino)-3-(S)-(1H-indol-3-yl)-propionamide
4176
	N-[3-(2-Fluoro-2′,5′-dimethyl-4′-{[(pyrimidin-4-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4177
	N-(3-{4′-[(2,2-Difluoro-2-pyridin-2-yl-ethylamino)-methyl]-2-fluoro-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4178
	N-[3-(2-Fluoro-4′-{[(5-(S)-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-
	ylmethyl)-amino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-
	ylmethyl]-acetamide
4179
	N-[3-(2-Fluoro-4′-{[(3-fluoro-pyridin-4-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4180
	N-[3-(2-Fluoro-4′-{[(5-methylamino-[1,2,4]thiadiazol-3-ylmethyl)-
	amino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-
	acetamide
4181
	N-[3-(4′-{[(6-Bromo-pyridin-3-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4182
	N-[3-(4′-{[(5-Bromo-pyridin-2-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4183
	N-[3-(2-Fluoro-4′-{[(isoxazol-3-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4184
	2-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-yl}-2-(R)-[9pyridin-4-ylmethyl)-amino]-acetamide
4185
	2-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-yl}-2-(R)-[(pyridin-2-ylmethyl)-amino]-acetamide
4186
	N-[3-(2-Fluoro-4′-{[(piperidin-4-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4187
	5-{4-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2-fluoro-
	phenyl}-pyridin-2-carboxylic acid (pyridin-2-ylmethyl)-amide
4188
	5-{4-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2-fluoro-
	phenyl}-pyridin-2-carboxylic acid (pyridin-4-ylmethyl)-amide
4189
	5-{4-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2-fluoro-
	phenyl}-pyridine-2-carboxylic acid (thiazol-2-ylmethyl)-amide
4190
	4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-3,2′-difluoro-
	biphenyl-4-carboxylic acid (pyridin-2-ylmethyl)-amide
4191
	4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-3,2′-difluoro-
	biphenyl-4-carboxylic acid [2-(3H-imidazol-4-yl)-ethyl]-amide
4192
	N-{3-[2-Fluoro-4′-(pyridin-2-ylmethoxymethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
4193
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-3-(1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-
	acrylamide
4194
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-3-(1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-
	acrylamide
4195
	N-(3-{3-Fluoro-4-[6-(pyridin-2-ylmethoxymethyl)-pyridin-3-yl]-
	phenyl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4196
	N-{3-[2-Fluoro-4′-(pyridin-4-ylmethoxymethyl)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
4197
	N-(3-{3-Fluoro-4-[5-(pyridin-2-ylmethoxymethyl)-pyridin-2-yl]-
	phenyl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4198
	N-{3-[2-Fluoro-4′-(1-oxy-pyridin-4-ylmethoxymethyl)-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4199
	N-[3-(2-Fluoro-4′-{1-(R)-hydroxy-2-[(oxazol-4-ylmethyl)-amino]-
	ethyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4200
	N-[3-(2-Fluoro-4′-{2-hydroxy-1-(S)-[(oxazol-4-ylmethyl)-amino]-
	ethyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4201
	N-[3-(2-Fluoro-4′-{1-(R)-hydroxy-2-[(pyridin-4-ylmethyl-amino]-
	ethyl}-bniphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4202
	N-[3-(2-Fluoro-4′-{2-hydroxy-1-(R)-[(pyridin-4-ylmethyl)-amino]-
	ethyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4203
	N-[3-(2-Fluoro-4′-{[(pyrimidin-5-ylmethyl)-amino]-methyl}-biphenyl-
	4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4204
	N-(3-{4′-[(Acetyl-[1,2,3]thiadiazol-4-ylmethyl-amino)-methyl]-2-
	fluoro-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4205
	4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-carboxylic acid (oxazol-4-ylmethyl)-amide
4206
	N-[3-(2-Fluoro-4′-{[([1,2,4]thiadiazol-3-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4207
	2-(4-Chloro-benzylamino)-thiazole-4-carboxylic acid {4′-[5-(S)-
	(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-
	ylmethyl}-amide
4208
	N-[3-(2-Fluoro-4′-{[(oxazol-5-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4209
	N-[3-(4′-{[([1,3]Dioxolan-2-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4210
	N-(3-{2-Fluoro-4′-[(oxiranylmethyl-amino)-methyl]-biphenyl-4-yl}-2-
	oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4211
	N-{3-[2-Fluoro-4′-(pyridin-4-ylmethylsulfanylmethyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4212
	N-{3-[2-Fluoro-4′-(pyridin-4-ylmethanesulfinylmethyl)-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4213
	3-(2-Fluoro-4′-{[(pyridin-4-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-
	5-(R)-hydroxymethyl-oxazolidin-2-one
4214
	N-{3-[2-Fluoro-4′-(pyridin-4-ylmethanesulfonylmethyl)-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4215
	N-(3-{2-Fluoro-4′-[(methyl-quinolin-3-ylmethyl-amino)-methyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4216
	N-{3-[2-Fluoro-4′-(pyridin-2-ylmethylsulfanylmethyl)-biphenyl-4-yl]-2-
	oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4217
	N-{3-[2-Fluoro-4′-(pyridin-2-ylmethanesulfinylmethyl)-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4218
	N-[3-(2-Fluoro-4′-{[(1-methyl-1H-indol-3-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4219
	N-[3-(2-Fluoro-4′-{[(tetrahydro-furan-3-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4220
	N-[3-(2-Fluoro-4′-{[(tetrahydro-furan-3-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4221
	N-[3-(2-Fluoro-4′-{[(thiophen-2-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4222
	N-{3-[2-Fluoro-4′-(N-furanm-2-ylmethyl-carbamimidoyl)-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4223
	5-{4-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2-fluoro-
	phenyl}-pyridine-2-carboxylic acid [2-(3H-imidazol-4-yl)-ethyl]-amide
4224
	4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-carboxylic acid ([1,2,4]oxadiazol-3-ylmethyl)-amide
4225
	4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-carboxylic acid ([1,2,4]thiadiazol-3-ylmethyl)-amide
4226
	N-[3-(2-Fluoro-4′-oxiranylmethylsulfanylmethyl-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
4227
	N-[3-(2-Fluoro-4′-{[2-(1H-imidazol-4-yl)-ethylamino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4228
	N-[3-(2-Fluoro-4′-{[2-(5-methyl-3H-indol-3-yl)-ethylamino]-methyl}-
	biphenyl-4-yl)-2-oxxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4229
	N-[3-(2-Fluoro-4′-{[(5-methyl-isoxazol-3-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4230
	3-(2-Fluoro-4′-{[(pyridin-4-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-
	5-(R)-[1,2,4]triazol-1-ylmethyl-oxazolidin-2-one
4231
	3-(2-Fluoro-4′-{[(pyridin-4-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-
	5-(R)-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-oxazolidin-2-one
4232
	N-[3-(2-Fluoro-4′-{1-(R/S)-[(pyridin-4-ylmethyl)-amino]-ethyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4233
	N-[3-(2-Fluoro-4′-{[([1,2,4]oxadiazol-3-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4234
	N-[3-(2-Fluoro-4′-{[(ocxazol-4-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4235
	N-{3-[3-Fluoro-4-(6-{[(oxazol-4-ylmethyl)-amino]-methyl}-pyridin-3-
	yl)-phenyl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4236
	N-(3-{2-Fluoro-4′-[N′-(pyridine-4-carbonyl)-hydrazinomethyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4237
	N-(3-{2-Fluoro-4′-[N′-(pyridin-3-carbonyl)-hydrazinomethyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4238
	N-[3-(2-Fluoro-4′-{[(oxazol-5-ylmethyl)-amino]-methyl}-biphenyl-4-
	yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4239
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-2-[1,2,3]triazol-1-yl-acetamide
4240
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-2-(4-hydroxymethyl-[1,2,3]triazol-1-yl)-
	acetamide
4241
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-2-[4-(2-hydroxy-butyl)-[1,2,3]triazol-1-yl]-
	acetamide
4242
	2-Methyl-thiazole-4-carboxylic acid {4′-[5-(S)-(acetylamino-methyl)-2-
	oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4243
	2-Methy-thiazole-4-carboxylic acid {4′-[5-(S)-(acetylamino-methyl)-2-
	oxo-oxaolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4244
	N-{3-[2-Fluoro-4′-([1,2,4]oxadiazol-3-ylmethylsulfanylmethyl)-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4245
	N-[3-(2-Fluoro-4′-{[(1-oxy-pyridin-4-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4246
	N-{3-[4′-(2-Benzylamino-1-(S)-hydroxy-ethyl)-2-fluoro-biphenyl-4-yl]-
	2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4247
	N-[3-(4′-{2-[Benzyl-(3-fluoro-propyl)-amino]-1-(S)-hydroxy-ethyl}-2-
	fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4248
	N-[3-(4′-{2-[Benzyl-(2-methylsulfanyl-ethyl)-amino]-1-(S)-hydroxy-
	ethyl}-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-
	acetamide
4249
	N-[3-(4′-{2-[Benzyl-(3-chloro-3,3-difluoro-propyl)-amino]-1-(S)-
	hydroxy-ethyl}-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-
	ylmethyl]-acetamide
4250
	N-(2-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-yl}-2-(S)-hydroxy-ethyl)-N-nbenzyl-acetamide
4251
	N-(3-{4′-[2-(Benzyl-methyl-amino)-1-(S)-hydroxy-ethyl]-2-fluoro-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4252
	N-{3-[3-Fluoro-4-(6-{[(isoxazol-4-ylmethyl)-amino]-methyl}-pyridin-
	3-yl)-phenyl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4253
	N-[3-(4′-{[(3-Bromo-isoxazol-5-ylmethyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4254
	N-[3-(2-Fluoro-4′-{2-[(isoxazol-4-ylmethyl)-amino]-1-methoxyimino-
	ethyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4255
	N-[3-(2-Fluoro-4′-{1-methoxyimino-2-[(oxazol-4-ylmethyl)-amino]-
	ethyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4256
	N-[3-(4′-{[3-(1-Benzyl-1H-[1,2,3]triazol-4-yl)-propylamino]-methyl}-
	2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4257
	N-[3-(2-Fluoro-4′-{[(2-fluoro-pyridin-3-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4258
	N-[3-(2-Fluoro-4′-{[3-(3H-[1,2,3]triazol-4-yl)-propylamino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4259
	N-(3-{2-Fluoro-4′-[(2-pyrrolidin-1-yl-ethylamino)-methyl]-biphenyl-4-
	yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4260
	N-[3-(3-Fluoro-4-morpholin-4-yl-phenyl)-2-oxo-oxazolidin-5-(S)-
	ylmethyl]-3-(5-pyrimidin-2-yl-pyridin-2-yl)-propionamide
4261
	N-[3-(2-Fluoro-2′-methoxy-4′-{[(pyridin-4-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4262
	N-(3-{2-Fluoro-4′-[(2-[1,2,3]triazol-1-yl-ethylamino)-methyl]-biphenyl-
	4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4263
	N-{3-[4′-(Benzyloxyamino-methyl)-2-fluoro-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
4264
	N-(3-{2-Fluoro-4′-[(3-[1,2,3]triazol-1-yl-propylamino)-methyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4265
	N-[3-(4′-{[Benzyloxy-(3-fluoro-propyl)-amino]-methyl}-2-fluoro-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4266
	N-[3-(2-Fluoro-4′-{[2-(3H-[1,2,3]triazol-4-yl)-ethylamino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4267
	N-[3-(2-Fluoro-4′-{[(3H-[1,2,3]triazol-4-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4268
	3-(2-Fluoro-4′-{[(3H-[1,2,3]triazol-4-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-5-(R)-[1,2,3]triazol-1-ylmethyl-oxazolidin-2-one
4269
	N-[3-(2-Fluoro-4′-{[(5-methyl-3H-[1,2,3]triazol-4-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4270
	N-[3-(4′-{[Bis(5-methyl-3H-[1,2,3]-triazol-4-ylmethyl)-amino]-
	methyl}-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-
	acetamide
4271
	N-(3-{2-Fluoro-4′-[N′-(4-methyl-[1,2,3]thiadiazole-carbonyl)-
	hydrazinomethyl]-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-
	acetamide
4272
	N-[3-(2-Fluoro-4′-{[(3-methyl-3H-[1,2,3]triazol-4-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4273
	N-[3-(2-Fluoro-4′-{[(2-methyl-2H-[1,2,3]triazol-4-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4274
	N-(3-{2-Fluoro-4′-[(3-fluoro-2-[1,2,3]triazol-1-yl-propylamino)-
	methyl]-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4275
	N-[3-(2-Fluoro-4′-{[2-(4-fluoro-phenyl)-2-(R/S)-hydroxy-ethylamino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4276
	N-[3-(2-Fluoro-4′-{[methyl-(3H-[1,2,3]triazol-4-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4277
	N-{3-[3-Fluoro-4-(6-{[(3H-[1,2,3]triazol-4-ylmethyl)-amino]-methyl}-
	pyridin-3-yl)-phenyl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4278
	N-[3-(2-Fluoro-4′-{[1-(R/S)-(3H-[1,2,3]triazol-4-yl)-ethylamino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4279
	N-[3-(2-Fluoro-4′-{[(pyrrolidin-2-(R/S)-ylmethyl)-amino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4280
	{4′-[5-(S)-(Acetylamino-methyl)-2-oxco-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-(1-methyl-1H-tetrazol-5-ylmethyl)-carbamic acid
	tert-butyl ester
4281
	{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-(2-methyl-2H-tetrazol-5-ylmethyl)-carbamic acid
	tert-butyl ester
4282
	N-[3-(2-Fluoro-4′-{[(1H-tetrazol-5-ylmethyl)-amino]-methyl}-biphenyl-
	4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4283
	N-[3-(2-Fluoro-4′-{[(1-methyl-1H-tetrazol--5-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4284
	N-[3-(2-Fluoro-4′-{[(2-methyl-2H-tetrazol-5-ylmethyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4285
	N-[3-(2-Fluoro-4′-{[(N-hydroxy-pyridine-4-carboxyimidoyl)-amino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
4286
	N-[3-(4′-{2-[Benzyl-(2-methanesulfonyl-ethyl)-amino]-1-(S)-hydroxy-
	ethyl}-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-
	acetamide
4287
	N-[3-(4′-{[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-
	ethanesulfonylamino]-methyl}-2-fluoro-biphenyl-4-yl)-2-oxo-
	oxazolidin-5-(S)-ylmethyl]-acetamide
4288
	N-{3-[4′-(Benzylsulfamoyl-methyl)-2-fluoro-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
4289
	5-Oxo-pyrrolidin-2-carboxylic acid {4′-[5-(S)-(acetylamino-methyl)-2-
	oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4290
	3-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-carbamoyl)-azetidine-1-carboxylic acid tert-butyl
	ester
4291
	Azetidine-3-carboxylic acid {4′-[5-(S)-(acetylamino-methyl)-2-oxo-
	oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4292
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-2-(R)-amino-3-(3H-imidazol-4-yl)-propionamide
4293
	2-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-amino)-2-pyridin-3-yl-acetamide
4294
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-2-amino-2-pyridin-3-yl-acetamide
4295
	2-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-carbamoyl)-azetidine-1-carboxylic acid tert-butyl
	ester
4296
	Azetidine-2-carboxylic acid {4′-[5-(S)-(acetylamino-methyl)-2-oxo-
	oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4297
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-2-(R)-amino-2-(4-fluoro-phenyl)-acetamide
4298
	4-[({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-amino)-methyl]-piperidine-1-carboxylic acid tert-
	butylester
4299
	N-{3-[2-Fluoro-4′-(1-[1,2,3]thiadiazol-4-ylmethyl-ureidomethyl)-
	biphenyl-4-yl]-2-oxo-oxazolidin-5-(S)-ylmethyl}-acetamide
4300
	N-(3-{4′[(Cyclopropylmethyl-amino)-methyl]-2-fluoro-biphenyl-4-yl}-
	2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4301
	4-(R)-Hydroxy-pyrrolidine-2-(S)-carboxylicacid {4′-[5-(S)-
	(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-
	ylmethyl}-amide
4302
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-2-(S)-amino-3-pyridin-2-yl-propionamide
4303
	[1-(S)-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-
	fluoro-biphenyl-4-ylmethyl}-carbamoyl)-2-pyridin-2-yl-ethyl]-carbamic
	acid tert-butyl ester
4304
	[1-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-carbamoyl)-cyclopropyl]-carbamic acid tert-butyl
	ester
4305
	2-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-carbamoyl)-2,5-dihydro-pyrrole-1-(S)-carboxylic
	acid tert-butylester
4306
	2,5-Dioxo-1H-pyrerole-2-(S)-carboxylic acid {4′-[5-(S)-(acetylamino-
	methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4307
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-2-(R)-amino-3-(1H-indol-3-yl)-propionamide
4308
	[1-(R)-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-
	fluoro-biphenyl-4-ylmethyl}-carbamoyl)-2-(1H-indol-3-yl)-ethyl]-
	carbamic acid tert-butyl ester
4309
	Pyrrolidine-2-(S)-carboxylic acid {4′-[5-(S)-(acetylamino-methyl)-2-
	oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4310
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-2-(R)-amino-3-pyridin-3-yl-propionamide
4311
	2-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmetrhyl}-carbamoyl)-4-(R)-hydroxy-pyrrolidin-1-(S)-
	carboxylic acid tert-butyl ester
4312
	2-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-amino)-3-(S)-(1H-indol-3-yl)-propionamide
4313
	2-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-amino)-3-(1H-imidazol-4-yl)-propionamide
4314
	N-(3-{2-Fluoro-4′-[(2-oxo-2-piperazin-1-yl-ethylamino)-methyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4315
	4-[2-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-
	fluoro-biphenyl-4-ylmethyl}-amino)-acetyl]-piperazine-1-carboxylic
	acid tert-butyl ester
4316
	N-(3-{2-Fluoro-4′-[(2-morpholin-4-yl-2-oxo-ethylamino)-methyl]-
	biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4317
	3-[({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-amino)-methyl]-pyrrolidin-1-carboxylic acid
	tert-butyl ester
4318
	N-(3-{2-Fluoro-4′-[(2-morpholin-4-yl-ethylamino)-methyl]-biphenyl-4-
	yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4319
	Cyclopropyanecarboxylic acid {4′-[5-(S)-(acetylamino-methyl)-2-oxo-
	oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4320
	N-(3-{2-Fluoro-4′-[(furan-3-ylmethyl-methyl-amino)-methyl]-2′-
	methoxy-biphenyl-4-yl}-2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
4321
	1-Amino-cyclopropanecarboxylic acid {4′-[5-(S)-(acetylamino-methyl)-
	2-oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
4322
	Piperazine-2-(R/S)-carboxylic acid {4′-[5-(S)-(acetylamino-methyl)-2-
	oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-amide
5001
	N-[3-(2-Fluoro-4′-{[2-(3H-[1,2,3]triazol-4-ylsulfanyl)-ethylamino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
5002
	N-[3-(2-Fluoro-4′-{[3-(3H-[1,2,3]triazol-4-ylsulfanyl)-propylamino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
5003
	N-[3-(2-Fluoro-4′-{[2-([1,3,4]thiazdiazol-2-ylsulfanyl)-ethylamino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
5004
	N-[3-(2-Fluoro-4′-{[2-(pyridin-2-ylsulfanyl)-ethylamino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
5005
	N-[3-(2-Fluoro-4′-{[2-(4H-[1,2,4]triazol-3-ylsulfanyl)-ethylamino]-
	methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
5006
	N-[3-(2-Fluoro-4′-{[2-(thiazol-2-ylsulfanyl)-ethylamino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
5007
	3-(2-Fluoro-4′-{[2-(3H-[1,2,3]triazol-4-ylsulfanyl)-ethylamino]-
	methyl}-biphenyl-4-yl)-5-(R)-[1,2,3]triazol-1-ylmethyl-oxazolidin-2-
	one
5008
	N-[3-(2-Fluoro-4′-{[2-(1H-imidazol-2-ylsulfanyl)-ethylamino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
5009
	N-[3-(2-Fluoro-4′-{[2-(pyrimidin-2-ylsulfanyl)-ethylamino]-methyl}-
	biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-ylmethyl]-acetamide
5010
	2-[2-({4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-
	fluoro-biphenyl-4-ylmethyl}-amino)-ethylsulfanyl]-1H-imidazole-4-
	carboxylic acid ethyl ester
5011
	N-[3-(2-Fluoro-4′-{[2-(S)-(hydroxy-3-(4H-[1,2,4]triazol-3-ylsulfanyl)-
	propylamino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-
	ylmethyl]-acetamide
5012
	N-(3-{2-Fluoro-4′-[(3-pyridin-4-yl-ureido)-methyl]-biphenyl-4-yl}-2-
	oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
5013
	N-(3-{2-Fluoro-4′-[3-(3-fluoro-phenyl)-ureidomethyl]-biphenyl-4-yl}-
	2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
5014
	N-{4′-[5-(S)-(Acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-
	biphenyl-4-ylmethyl}-2-(2,4-dichloro-phenoxy)-acetamide
5015
	N-[3-(4′-{[3-(3-Chloro-5-trifluoromethyl-pyridin-2-ylamino)-
	propylamino]-methyl}-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-(S)-
	ylmethyl]-acetamide
6001
	N-(3-{2-Fluoro-4′-[3-(3-imidazol-1-yl-propyl)-ureido]-biphenyl-4-yl}-
	2-oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
6002
	N-{3-[2-Fluoro-4′-(3-thiazol-2-ylmethyl-ureido)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
6003
	N-(3-{2-Fluoro-4′-[3-(2-pyridin-2-yl-ethyl)-ureido]-biphenyl-4-yl}-2-
	oxo-oxazolidin-5-(S)-ylmethyl)-acetamide
6004
	N-{3-[2-Fluoro-4′-(3-pyridin-4-ylmethyl-ureido)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide
6005
	N-{3-[2-Fluoro-4′-(3-pyridin-2-ylmethyl-ureido)-biphenyl-4-yl]-2-oxo-
	oxazilidin-5-(S)-ylmethyl}-acetamide
6006
	N-{3-[2-Fluoro-4′-(3-pyridin-4-yl-ureido)-biphenyl-4-yl]-2-oxo-
	oxazolidin-5-(S)-ylmethyl}-acetamide

[0160] Nuclear magnetic resonance (NMR) spectra were obtained on a Bruker Avance 300 or Avance 500 spectrometer, or in some cases a GE-Nicolet 300 spectrometer. Common reaction solvents were either high performance liquid chromatography (HPLC) grade or American Chemical Society (ACS) grade, and anhydrous as obtained from the manufacturer unless otherwise noted. “Chromatography” or “purified by silica gel” refers to flash column chromatography using silica gel (EM Merck, Silica Gel 60, 230-400 mesh) unless otherwise noted.

[0161] Scheme 1 depicts the synthesis of various biaryl intermediates useful in producing compounds of the present invention. Known iodoaryl oxazolidinone intermediate 50 (see U.S. Pat. Nos. 5,523,403 and 5,565,571) is coupled to a substituted aryl boronic acid (the Suzuki reaction) to produce biaryl alcohol 51. Mesylate 52, azide 53, and amine 54 are then synthesized using chemistry well known to those skilled in the art.
Synthesis of alcohol 51

[0162] A suspension of N-[3-(3-fluoro-4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 50 (14.0 g, 37 mmol) in toluene (120 mL) was treated with 4-(hydroxymethyl) phenylboronic acid (7.87 g, 51.8 mmol, 1.4 equiv), potassium carbonate (K₂CO₃, 15.32 g, 111 mmol, 3.0 equiv), ethanol (EtOH, 40 mL), and H₂O (40 mL) at 25° C., and the resulting mixture was degassed three times under a steady stream of argon at 25° C. Tetrakis(triphenylphosphine)palladium (Pd(PPh₃)₄, 2.14 g, 1.85 mmol, 0.05 equiv) was subsequently added to the reaction mixture, and the resulting reaction mixture was degassed three times again before being warmed to gentle reflux for 6 h. When thin layer chromatography (TLC) and HPLC showed the coupling reaction was complete, the reaction mixture was cooled to room temperature before being treated with H₂O (240 mL). The resulting mixture was then stirred at room temperature for 10 min before being cooled to 0-5° C. for 1 h. The solid precipitates were collected by filtration, washed with H₂O (2×100 mL) and 20% ethyl acetate (EtOAc)/hexane (2 X 50 mL), and dried in vacuo. The crude desired N-[3-(2-Fluoro4′ -hydroxymethyl-biphenyl4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 51 (12.50 g, 94% yield) was obtained as off-white solids. This material was found to be essentially pure by HPLC and ¹H NMR and was directly used in the subsequent reaction without further purification. ¹H NMR (300 MHz, DMSO-d₆) δ1.76 (s, 3H, COCH₃), 3.35 (t, 2H, J=5.4 Hz), 3.69 (dd, 1 H, J=6.4, 9.2 Hz), 4.08 (t, 1H, J =9.1 Hz), 4.46 (d, 2 H, J=5.7 Hz, CH₂OH), 4.68 (m, 1 H), 5.16 (t, 1 H, J=5.7 Hz, OH), 7.25-7.52 (m, 7 H, aromatic-H), 8.18 (t, 1 H, J=5.8 Hz, NHCOCH₃). LCMS (ESI) m/e 359 (M+H)+.

Synthesis of mesylate 52

[0163] A suspension of 51 (12.49 g, 34.90 mmol) in methylene chloride (CH₂Cl₂, 150 mL) was treated with triethylamine (Et₃N, 7.07 g, 9.7 mL, 70 mmol, 2.0 equiv) at 25° C., and the resulting mixture was cooled to 0-5° C. before being treated dropwise with methanesulfonyl chloride (4.80 g, 3.24 mL, 41.9 mmol, 1.2 equiv) at 0-5° C. The resulting reaction mixture was subsequently stirred at 0-5° C. for 2 h. When TLC and HPLC showed the reaction was complete, the reaction mixture was treated with H₂O (100 mL) at 0-5° C. The mixture was then concentrated in vacuo to remove most of the CH₂Cl₂, and the resulting slurry was treated with H₂O (150 mL). The mixture was stirred at room temperature for 10 min before being cooled to 0-5° C. for 30 min. The solid precipitates were collected by filtration, washed with H₂O (2×100 mL) and 20% EtOAc/hexane (2 X 50 mL), and dried in vacuo. The crude desired methanesulfonic acid 4′-[5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl4-ylmethyl ester 52 (11.84 g, 78% yield) was obtained as off-white solids, which by TLC and HPLC was found to be essentially pure and was directly used in the subsequent reaction without further purification. LCMS (ESI) m/e 437 (M+H)+.

Synthesis of azide 53

[0164] A solution of 52 (9.27 g, 21.26 mmol) in anhydrous N,N-dimethylformamide (DMF, 50 mL) was treated with sodium azide (NaN₃, 5.53 g, 85.04 mmol, 4.0 equiv) at 25° C., and the resulting reaction mixture was warmed to 70-80° C. for 4 h. When TLC and HPLC showed the reaction was complete, the reaction mixture was cooled to room temperature before being treated with H₂O (150 mL). The resulting mixture was stirred at room temperature for 10 min before being cooled to 0-5° C. for 1 h. The solid precipitates were collected by filtration, washed with H₂O (2×100 mL) and 20% EtOAc/hexane (2 X 50 mL), and dried in vacuo. The crude desired N-[3-(4′-azidomethyl-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 53 (7.16 g, 88% yield) was obtained as off-white solids. The material was found to be essentially pure by TLC and HPLC and was directly used in the subsequent reaction without further purification. LCMS (ESI) m/e 384 (M+H)+.

Synthesis of amine 54

[0165] A solution of 53 (7.16 g, 18.69 mmol) in tetrahydrofaran (THF) (100 mL) was treated with triphenylphosphine (PPh₃, 5.88 g, 22.43 mmol, 1.2 equiv) and H₂O (3.6 g, 3.6 mL, 0.2 mmol, 11.0 equiv) at 25° C., and the resulting reaction mixture was warmed to 50-55° C. for 12 h. When TLC and HPLC showed the reduction reaction was complete, the reaction mixture was cooled to room temperature before the solvents were removed in vacuo. The residue was directly purified by flash column chromatography (0-15% MeOH-CH₂Cl₂ gradient elution) to afford the desired N-[3-(4′-Aminomethyl-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 54 (5.82 g, 87% yield) as off-white crystals, which were of sufficient purity to be directly used in subsequent reactions. ¹ H NMR (300 MHz, DMSO-d₆) δ1.85 (s, 3H, COCH₃), 3.04 (br. s, 2 H, NH₂), 3.44 (t, 2 H, J=5.4 Hz), 3.78 (m, 3 H), 4.18 (t, 1 H, J=9.1 Hz), 4.77 (m, 1 H), 7.25-7.60 (m, 7 H, aromatic-H), 8.20 (t, 1 H, J=5.8 Hz, NHCOCH₃). LCMS (ESI) m/e 359 (M+2 H)²⁺.

[0166] Scheme 2 illustrates the synthesis of triazole 1001 and imidazole 1002. Aryl bromide 60 was converted to boronic acid 61 which was used in a Suzuki coupling with aryl iodide 50 to afford alcohol 63 after desilylation. The alcohol was converted to mesylate 64 and then to azide 65. The cycloaddition of azide 65 with trimethylsilylacetylene followed by desilylation afforded triazole 1001. Alkylation of mesylate 64 with imidazole yielded compound 1002.
Synthesis of bromide 60

[0167] To a solution of 4-bromophenethyl alcohol (5.60 g, 27.9 mmol), imidazole (3.80 g, 55.7 mmol) and a catalytic amount of 4-dimethylaminopyridine (DMAP) in DMF (55 mL) was added t-butyldiphenylchlorosilane (TBDPSCl, 7.20 mL, 27.9 mmol) at 0° C. and the mixture was stirred at ambient temperature for 72 h. The reaction was quenched with ice cold water (50 mL) and extracted with ether (4×50 mL). The combined etheral layer was washed with water (4×100 mL), dried over anhydrous sodium sulfate (Na₂SO₄), concentrated and purified by flash chromatography (2% ethyl acetate in hexanes) to yield 10.6 g of 60.

Synthesis of boronic acid 61

[0168] To a solution of 60 (10.5 g, 24.0 mmol) in THF (50 mL) was added n-butyl lithium (n-BuLi, 2.5 M in hexane, 11.5 mL, 28.8 mmol) at −78° C. and the mixture was stirred for 1 h before the addition of trimethyl borate (3.54 mL, 31.2 mmol). The solution was then stirred overnight at ambient temperature and quenched with 1 M potassium hydrogen sulfate (KHSO₄, 25 mL). The resulting mixture was extracted with CH₂Cl₂ (3×50 mL), washed with brine (3×100 mL), dried (anhydrous Na₂SO₄), concentrated and purified by flash chromatography (25% ethyl acetate in hexanes) to yield 5 g of boronic acid 61 as mixture of acid and cyclic anhydrides.

Synthesis of alcohol 63

[0169] To a mixture of boronic acid 61 (4.7 g, 11.7 mmol), known oxazolidinone 50 (4.00 g, 10.6 mmol; see U.S. Pat. Nos. 5,523,403 and 5,565,571), potassium carbonate (K₂CO₃, 4.40 g, 31.8 mmol) and Pd(PPh₃)₄ (0.613 g, 5 mol %) was added toluene (90 mL), ethanol (30 mL) and H₂O (30 mL). The reaction mixture was refluxed overnight under argon atmosphere, concentrated and redissolved in CH₂Cl₂ (100 mL). The organic phase was washed with brine solution (2×100 mL), dried (anhydrous Na₂SO₄), concentrated and used for the next step without further purification. To a solution of this crude material in THF (70 mL) was added tetrabutylammonium fluoride (TBAF, 20 mL, 20 mmol) and the mixture was stirred overnight at ambient temperature. The reaction mixture was concentrated and washed with water (4×100 mL) to yield 3.5 g of 63. LCMS (ESI) m/z 373 (M+H).

Synthesis of mesylate 64 and azide 65

[0170] To a solution of 63 (1.0 g, 2.7 mmol) in CH₂Cl₂ (15 mL), DMF (4 mL) and N,N-diisopropylethylamine (Hunig's base, 0.75 mL, 4.05 mmol) was added methanesulfonyl chloride (0.32 mL, 2.7 mmol) at 0° C. After 2 h the reaction mixture was poured into CH₂Cl₂ (150 mL) and the organic layer was washed with water (3×100 mL), dried, concentrated to afford 64 as a solid. The crude solid 64 thus obtained was heated with NaN₃ (0.35 g, 5.4 mmol) at 90° C. overnight. The reaction mixture was poured into ethyl acetate (100 mL). The ethyl acetate layer was washed with water (3×50 mL), dried and concentrated to yield 1.1 g of pure azide 65. LCMS (ESI) m/z 398 (M+H).

Synthesis of triazole 1001

[0171] A solution of azide 65 (100 mg, 0.252 mmol) and trimethylsilylacetylene (0.072 mL, 0.504 mmol) in DMF (3 mL) was heated at 90° C. until the azide was consumed. The reaction mixture was concentrated and treated with TBAF (1 mL, 1 mmol) and acetic acid (0.028 mL, 0.504 mmol) in THF (3 mL). The solution was stirred for 72 h and concentrated. The crude product was purified by flash chromatography using 4% methanol (MeOH) in CH₂Cl₂ to yield 85 mg of 1001. LCMS (ESI) m/z 424 (M+H).

Synthesis of imidazole 1002

[0172] To a solution of imidazole (70 mg, 1.0 mmol) in DMF (5 mL) was added sodium hydride (NaH, 60%, 41 mg, 1 mmol) at 0° C. and the mixture was stirred for 30 minutes before the addition of mesylate 64 (114 mg, 0.250 mmol). The resulting solution was heated to 80° C. for 3h, concentrated and purified by flash chromatography (5% MeOH in CH₂Cl₂). After trituration with ether, the residue afforded 40 mg of 1002. LCMS (ESI) m/z 423 (M+H).

[0173] Scheme 3 illustrates the synthesis of compounds 1003-1006. Mesylate 52 served as alkylating agent for piperazine intermediates 68, 69 and 70 to afford compounds 1003, 1004 and 1006 respectively. Mesylate 67 was employed to alkylate piperazine intermediate 69 to provide compound 1005.
Synthesis of mesylate 67

[0174] Mesylate 67 was synthesized by coupling iodide 50 and 4-formyl-3-fluorophenylboronic acid following the procedure described above for the synthesis of N-[3-(2-fluoro4′-hydroxymethyl-biphenyl4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide (see Example 1). The biaryl aldehyde obtained (1.0 g, 2.67 mmol) was suspended in 40 mL methanol and the mixture was cooled to 0° C. Sodium borohydride (0.112 g, 2.943 mmol) was added, and the mixture was stirred for 50 min. Water was added (20 mL), and after stirring another 20 min the mixture was partitioned between methylene chloride and brine. The aqueous phase was extracted twice with methylene chloride. The aqueous phase was acidified to pH 7, then extracted twice with methylene chloride. The combined organic phase was washed with brine, dried over Na₂SO₄, and concentrated. The crude material was azeotroped with toluene to afford the expected alcohol (900 mg).

[0175] The above alcohol (900 mg) was dissolved in methylene chloride (20 mL), DMF (13 mL) and Hunig's base (1.23 mL) and the mixture was cooled to 0° C. Methanesulfonyl chloride (557 uL, 7.20 mmol) was added and the mixture was stirred for 1.5 h at 0° C. LCMS indicated a mixture of desired mesylate and some of the corresponding benzyl chloride. The mixture was stirred for another 30 min and then concentrated. The residue was treated with 400 mL water, and the precipitate was filtered and washed with water. Drying under vacuum overnight yielded 750 mg crude mesylate 67 (as a mixture with some of the corresponding chloride).

Synthesis of piperazine 68

[0176] A solution of tert-butyl-1-piperazine carboxylate (1 g, 5.4 mmol), bromoacetamide (820 mg, 5.94 mmol) and Hunig's base (1.2 mL, 7.2 mmol) in a mixture of CH₂Cl₂ (10 mL) and MeOH (10 mL) was heated to reflux for 4 h. The reaction mixture was concentrated and the crude product thus obtained was purified by flash chromatography (19 :1 :0.01 CH₂Cl₂/MeOH/ NH₄OH) to yield 1.3 g of pure BOC-protected piperazinyl acetamide. To a solution of the acetamide (250 mg, 1 mmol) in CH₂Cl₂ (10 mL) was added trifluoroacetic acid (TFA, 5 mL) at 0° C. and the mixture was stirred at that temperature for 2 h. The reaction mixture was concentrated to yield 68 which was used for subsequent reactions without further purification.

Synthesis of piperazine 69

[0177] A solution of tert -butyl-1-piperazine carboxylate (1 g, 5.4 mmol), bromoacetonitrile (0.5 mL, 5.94 mmol) and Hunig's base (1.2 mL, 7.2 mmol) in a mixture of CH₂Cl₂ (10 mL) and MeOH (10 mL) was stirred at ambient temperature for 4 h. The reaction mixture was concentrated and the crude product thus obtained was purified by flash chromatography (19:1:0.01 CH₂Cl₂/MeOH/NH₄OH) to yield 1.3 g of pure BOC-protected piperazinyl acetonitrile. To a solution of the piperazinyl acetonitrile (300 mg, 1.3 mmol) in CH₂Cl₂ (10 mL) was added TFA (5 mL) at 0° C. and the mixture was stirred at that temperature for 2 h. The reaction mixture was concentrated to yield 69 which was used for subsequent reactions without further purification.

Synthesis of compound 1003

[0178] A solution of mesylate of 52 (138 mg, 0.320 mmol) and 68 (˜1 mmol) in Hunig's base (2 mL) and DMF (8 mL) was heated to 90° C. for 2 h. Then the solution was concentrated and purified by flash chromatography over silica gel (20:1:0.01 CH₂Cl₂/MeOH/NH₄OH) to yield 1003. LCMS (ESI) m/z 484 (M+H)+.

Synthesis of compound 1004

[0179] Compound 1004 was synthesized from mesylate 52 and piperazine intermediate 69 in the same manner as described above for the synthesis of compound 1003. LCMS (ESI) m/z 466 (M+H)+.

Synthesis of compound 1005

[0180] Compound 1005 was synthesized from mesylate 67 and piperazine intermediate 69 in the same manner as described above for the synthesis of compound 1003. LCMS (ESI) m/z 484 (M+H)+.

Synthesis of compound 1006

[0181] Compound 1006 was synthesized from mesylate 52 and available piperazine intermediate 70 in the same manner as described above for the synthesis of compound 1003. LCMS (ESI) m/z 455 (M+H)+.

[0182] Scheme 4 illustrates the synthesis of compounds 1007-1010. Mesylate 52 was converted to nitrile 71, which was subsequently transformed to tetrazole 1007. Mesylate 52 served as alkylating agent for the anion derived from imidazole to afford imidazole derivative 1008. Mesylate 67 was converted to azide 72, which was then subsequently converted to triazole 1009. Mesylate 67 served as alkylating agent for the anion derived from imidazole to afford imidazole derivative 1010.
Synthesis of tetrazole 1007

[0183] To a solution of mesylate 52 (2.0 g, 4.6 mmol) in DMF (30 mL) was added sodium cyanide (NaCN, 0.45 g, 9.2 mmol) and the mixture was heated to 70° C. for 3 h. The reaction mixture was cooled to ambient temperature and poured into water (800 mL). The solid thus obtained was filtered and passed through a small bed of silica gel (CH₂Cl₂: MeOH=12:1) to yield 1.8 g of nitrile 71. LCMS (ESI) m/z 368 (M+H)+.

[0184] A mixture of 71 (100 mg, 0.272 mmol), NaN₃ (40 mg, 0.598 mmol) and ammonium chloride (NH₄Cl, 32 mg, 0.598 mmol) in DMF (2 mL) was heated to 90° C. for 3 days. The reaction mixture was concentrated and purified by flash chromatography (10% MeOH in CH₂Cl₂) to yield 35.6 mg of tetrazole 1007. LCMS (ESI) m/z 411 (M+H)+.

Synthesis of imidazole 1008

[0185] To a solution of imidazole (37.4 mg, 0.550 mmol) in DMF (5 mL) was added NaH (60%, 20 mg, 0.50 mmol) at 0° C. and the mixture was stirred for 30 minutes before the addition of mesylate 52 (200 mg, 0.459 mmol). The resulting solution was heated to 60° C. for 2 h and poured into water (75 mL). The aqueous suspension was extracted with 10% MeOH in CH₂Cl₂ (3×75 mL) and the combined organic layer was washed with saturated NH₄Cl solution (2×100 mL). The organic layer was dried (anhydrous Na₂SO₄), concentrated and triturated with ether to yield 170 mg of imidazole 1008. LCMS (ESI) m/z 409 (M+H)+.

Synthesis of azide 72

[0186] Crude mesylate 67 (100 mg, 0.224 mmol; as a mixture with some corresponding benzyl chloride) was dissolved in DMF (10 mL) and sodium azide (114.6 mg, 1.762 mmol) was added. The mixture was stirred at room temperature for 14 h, and then partitioned between ethyl acetate and water. The organic phase was washed with water, dried over Na₂SO₄, and concentrated to provide azide 72 as a solid (190 mg).

Synthesis of triazole 1009

[0187] Compound 1009 was synthesized from azide 72 and trimethylsilylacetylene in the same manner as described above for the synthesis of triazole 1001. LCMS (ESI) m/z 428 (M+H)+.

Synthesis of imidazole 1010

[0188] Compound 1010 was synthesized from mesylate 67 and imidazole in the same manner as described above for the synthesis of imidazole derivative 1008. LCMS (ESI) m/z 427 (M+H)+.

[0189] Scheme 5 illustrates the synthesis of compounds 1011-1015. The cycloaddition of azide 53 with alkynes 74-76 afforded triazoles 1011-1013 respectively. The cycloaddition of azide 53 with alkyne 77 gave BOC-protected intermediate 78 which was subsequently cleaved to provide derivative 1014. The cycloaddition of azide 53 with trimethylsilylacetylene, followed by desilylation, yielded triazole 1015.
Synthesis of triazole 1011

[0190] A solution of azide 53 (0.10 g, 0.26 mmol) in propargyl amine 74 (0.50 mL) was treated with copper iodide (0.05 g, 0.26 mmol) and was stirred at 23° C. for 0.5 h. The reaction mixture was diluted with CH₂Cl₂ and MeOH and purified by flash chromatography and preparative TLC to afford 1011 as a brown solid (0.027 g; 24%). LCMS (ESI) m/z 439 (M+H)+.

Synthesis of triazole 1012

[0191] A solution of azide 53 (0.10 g, 0.26 mmol) in N-methylpropargyl amine 75 (0.50 mL) was treated with copper iodide (5.00 mg, 0.026 mmol) and stirred at 23° C. for 12 h. The solvent was removed in vacuo, and the crude product was purified by preparative TLC to afford 1012 as a brown solid (0.038 g; 32%). LCMS (ESI) m/z 453 (M+H)+.

Synthesis of triazole 1013

[0192] A solution of azide 53 (0.10 g, 0.26 mnnol) in N, N-dimethylpropargyl amine 76 (0.056 mL, 0.520 mmol) was treated with copper iodide (5.00 mg, 0.026 mmol) and stirred at 23° C. for 12 h. The solvent was removed in vacuo, and the crude product was purified by flash chromatography to afford 1013 as a yellow film (0.073 g; 60%). LCMS (ESI) m/z 467 (M+H)+.

Synthesis of alkyne 77

[0193] A solution of propargyl amine 74 (0.34 mL, 5.0 mmol) in methylene chloride (25 mL) was treated with BOC-glycine (0.96 g, 5.5 mmol) and EDCl (1.1 g, 5.5 mmol) and stirred at 23° C. for 0.5 h. The reaction mixture was diluted with CH₂Cl₂, washed with 1.0 M HCl (aqueous), washed with saturated aqueous sodium bicarbonate (NaHCO₃), dried over Na₂SO₄, and the solvent evaporated in vacuo to afford alkyne 77 (0.51 g; 48%).

Synthesis of triazole 1014

[0194] A solution of azide 53 (0.15 g, 0.39 mmol) in THF (2 mL) was treated with alkyne 77 (0.17 g, 0.78 mmol) and copper iodide (7.00 mg, 0.039 mmol) and stirred at 23° C. for 16 h. The solvent was removed in vacuo, and the crude product was purified by flash chromatography to afford 78 as a white powder (0.16 g; 68%). LCMS (ESI) m/z 618 (M+Na)+.

[0195] A solution of 78 (0.15 g, 0.25 mmol) was treated with HCl (1.3 mL of 4.0 M solution in dioxane) and was stirred at 23° C. for 2 h. The solvent was removed in vacuo, and the residue twice redissolved in methylene chloride and evaporated to afford 1014 as a white film (0.14 g, 100%). LCMS (ESI) m/z 496 (M+H)+.

Synthesis of triazole 1015

[0196] A solution of azide 53 (0.75 mg, 2.0 mmol) in DMF (10 mL) was treated with trimethylacetylene (2.3 mL, 20 mmol) and was stirred at 90° C. for 12 h. The reaction mixture was cooled to 23° C. and the solvent was removed in vacuo to afford the expected silyl-substituted triazole as a brown foam (0.24 mg; 25%). LCMS (ESI) m/z 482 (M+H)+.

[0197] A solution of the above silyl-substituted triazole (0.050 g, 0.10 mmol) in THF (0.20 mL) was treated with acetic acid (6 μL, 0.10 mmol) and tetrabutylammonium fluoride (0.21 mL of 1.0 M solution in THF) and was stirred at 23° C. for 16 h. The reaction mixture was diluted with CH₂Cl₂, washed with water, dried (Na₂SO₄), and the solvent removed in vacuo. The crude product was purified to afford 1015 as a white powder (0.020 g; 47%). LCMS (ESI) m/z 432 (M+Na)+.

[0198] Scheme 6 illustrates the synthesis of compounds 1016-1017. Hydroxyamidine 79 was converted to bromide 80 which was subsequently coupled to boronate 81 to afford compound 1016. Hydroxyamidine 79 was transformed to oxadiazole 82, which was coupled to boronate 81 to afford compound 1017.
Synthesis of hydroxyamidine 79

[0199] A solution of 4-bromophenylacetonitrile (10 g, 54 mmol) in methanol (100 mL) was treated with sodium bicarbonate (2.2 g, 57 mmol) and hydroxylamine hydrochloride (4.0 g, 57 mmol) and refluxed for 1.5 h. Additional sodium bicarbonate (0.21 g, 5.4 mmol) and hydroxylamine hydrochloride (0.38 g, 5.4 mmol) were added, and the reaction mixture was refluxed for 12 h. The reaction mixture was cooled to 23° C. and the solvent removed in vacuo to afford hydroxyamidine 79 as a blue powder (4.0 g; 34%).

Synthesis of bromide 80

[0200] A solution of hydroxyamidine 79 (0.20 g, 0.91 mmol) in 1,4-dioxane (1 mL) was treated with 1,1′-carbonyldiimidazole (0.18 g, 1.1 mmol) and diazabicycloundecene (DBU, 0.15 mL, 0.97 mmol) and stirred at 105° C. for 1 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The water layer was treated with 1.0 M HCl (aqueous) until the pH was 2, and then extracted with ethyl acetate. The organic layer was dried over Na₂SO₄, and the solvent removed in vacua to afford bromide 80 as a yellow powder (0.11 g; 49%).

Synthesis of boronate 81

[0201] A suspension of N-[3-3-fluoro4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl]acetamide 62 (20.0 g, 52.8 mmol) in anhydrous 1,4-dioxane (130 mL) was treated with 4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (10.2 g, 11.6 mL, 80.0 mmol) and triethylamine (16.0 g, 22.4 mL, 158.4 mmol) at room temperature, and the resulting reaction mixture was degassed three times under a steady stream of argon before being treated with dichloro[1,1′-bis(diphenylphosphino)ferrocene] palladium (II) (Pd(dppf)₂Cl₂, 1.32 g, 1.6 mmol, 0.03 equiv) at room temperature. The reaction mixture was then degassed three times again under a steady stream of argon before being heated to reflux for 7 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was cooled down to room temperature before being treated with water (100 mL) and ethyl acetate (100 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with water (2×50 mL) and saturated aqueous NaCl solution (50 mL), dried over magnesium sulfate (MgSO₄), and concentrated in vacuo. The residual brown oil was further dried in vacuo to afford the crude desired N- {3-[3-fluoro-4-(4,4,5,5-tetramethyl-[ 1,3,2]dioxaborolan-2-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}acetamide 81 (18.8 g, 20.0 g theoretical, 94%) as a brown solid which was of sufficient purity to be used in subsequent reactions.

Synthesis of compound 1016

[0202] A solution of boronate ester 81 (0.085 g, 0.220 mmol), bromide 80 (0.055 g, 0.220 mmol), and potassium carbonate (0.12 g, 0.90 mmol) in dioxane (1.4 mL), ethanol (0.46 mL) and water (0.46 mL) was degassed and treated with Pd(dppf)C1₂ (6.0 mg, 6.7 μmol), degassed again, and heated at 80° C. for 1.5 h. The reaction mixture was diluted with CH₂Cl₂ and water, and the precipitate in the water layer was recovered by vacuum filtration to afford 1016 as a grey powder (0.034 g; 36%). LCMS (ESI) m/z 427 (M+H)+.

Synthesis of bromide 82

[0203] A solution of hydroxyamidine 79 (0.25 g, 1.1 mmol) in pyridine (5 mL) was cooled to 0° C. and treated with a solution of acetic anhydride (0.11 mL, 1.1 mmol) in pyridine (5 mL) and then stirred at 120° C. for 1.5 h. The reaction mixture was diluted with ethyl acetate, washed with 1.0 M HCl (aqueous), washed with saturated aqueous sodium bicarbonate, dried over Na₂SO₄, and the solvent evaporated in vacuo. The crude product was purified by flash chromatography to afford bromide 82 as a clear film (0.10 g; 36%).

Synthesis of compound 1017

[0204] A solution of boronate ester 81 (0.15 g, 0.40 mmol), bromide 82 (0.10 g, 0.40 mmol), and potassium carbonate (0.22 g, 1.6 mmol) in dioxane (2.5 mL), ethanol (0.83 mL) and water (0.83 mL) was degassed and treated with Pd(dppf)Cl₂(10.0 mg, 0.012 mmol), degassed again, and stirred at 80° C. for 2 h. The reaction mixture was diluted with CH₂Cl₂ and washed with water. The water layer was extracted with 2×CH₂Cl₂, dried over Na₂SO₄, and the solvent evaporated in vacuo. The crude product was purified by flash chromatography and preparative TLC to afford 1017 as a white powder (0.054 g; 32%). LCMS (ESI) m/z 425 (M+H)+.

[0205] Scheme 7 illustrates the synthesis of compounds 1018-1019. Known aryl iodide 83 was coupled to 4-hydroxymethylboronic acid to afford biaryl alcohol 84. Alcohol 84 was converted to azide 85, which was used in alkyne cycloaddition reactions to afford triazoles 1018 and 1019.
Synthesis of azide 85

[0206] Known aryl iodide 83 (Gravestock, M.B., International Patent Application WO9910342) (1.00 g, 2.52 mmol) was dissolved in 6 mL DMF. 4-Hydroxymethyl-phenylboronic acid (0.461 g, 3.03 mmol) was added, followed by potassium phosphate (K₃PO₄, 0.804 g, 3.79 mmol) and Pd(PPh₃)₄ (0.292 g, 0.253 mmol). The mixture was degassed by evacuating the air from the flask, and refilling with argon (3 times), and then heated to 100° C. for 4 hours. The mixture was allowed to cool and was then partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate, and the combined organic phase was washed with brine, dried over MgSO₄, and evaporated. The residue was chromatographed on silica using a gradient mixture of methanol/methylene chloride (1% to 8%) to afford alcohol 84 (0.315 g, 0.838 mmol; 33%) as an ivory solid. An analytical sample was obtained by recrystallizing the material from methanol/methylene chloride/pentane. LCMS (ESI) m/z 377.

[0207] Alcohol 84 (0.889 g, 2.36 mmol) was suspended in 0.3 mL methylene chloride and 0.3 mL DMF. Triethylamine (0.66 mL, 4.74 mmol) was added, and the mixture was cooled to 0° C. Methanesulfonyl chloride (0.260 mL, 3.36 mmol) was added dropwise, and the mixture was stirred for 25 minutes. The mixture was then partitioned with ethyl acetate and water, and the organic layer was washed with brine, dried over MgSO₄, and evaporated. The residue was dissolved in 3 mL DMF, and sodium azide (0.384 g, 5.91mmol) was added. The mixture was heated to 70° C. for 4 hours. The reaction mixture was partitioned with ethyl acetate and water, and the organic layer was washed with brine, dried over MgSO₄, and evaporated. The residue was chromatographed on silica using a gradient mixture of methanol/methylene chloride (1% to 4%) to afford azide 85 (0.480 g, 1.20 mmol; 51%) as a tan solid. LCMS (ESI) m/z 402.

Synthesis of triazole 1018

[0208] Azide 85 (0.084 g, 0.209 mmol) was dissolved in 0.7 mL THF and propargyl alcohol (25 μL, 0.400 mmol) was added, followed by Hunig's base (73 μL, 0.400 mmol) and copper(I) iodide (0.040 g, 0.210 mmol). The mixture was allowed to stir overnight at room temperature, and then was placed in a −20° C. freezer for 2 days. The mixture was then partitioned with ethyl acetate and water, and the aqueous layer was extracted with ethyl acetate and then 2% methanol/methylene chloride. The combined organic layer was washed with brine, dried over MgSO₄ and evaporated. The residue was chromatographed on silica using a gradient mixture of methanol/methylene chloride (1% to 8%) to afford triazole 1018 (0.060 g, 0.131 mmol; 63%) as an ivory solid. LCMS (ESI) m/z 458.

Synthesis of triazole 1019

[0209] Azide 85 (0.135 g, 0.337 mmol) was dissolved in 1.5 mL THF and dimethyl-prop-2-ynyl-amine (72 μL, 0.674 mmol) was added, followed by i-Pr₂NEt (117 μL, 0.674 mmol) and copper(I)iodide (0.064 g, 0.337 mmol). The mixture was allowed to stir overnight at room temperature (the solvents evaporated overnight with positive pressure from argon gas). The residue was suspended in ethyl acetate and methylene chloride and filtered through celite. The pad of celite was washed with ethyl acetate and methylene chloride, and the combined organic washes were evaporated. The residue was chromatographed on silica using a gradient mixture of methanol/methylene chloride (0% to 14%) and the product obtained was triturated with methylene chloride and pentane. The tan solid was collected to afford triazole 1019 (0.072 g, 0.149 mmol; 44%). LCMS (ESI) m/z 485.

[0210] Scheme 8 illustrates the synthesis of compounds 1020-1021. Bromoketone 86 was subjected to alkylation with thioureas 87a and 87b to afford thiazoles 88a and 88b respectively. Coupling of 88a and 88b with boronate 81 yielded thiazoles 1020 and 1021.
Synthesis of thiazole 88a

[0211] Bromoketone 86 (0.29 g, 1.0 mmol) was dissolved in dioxane (10 mL). Thiourea 87a (0.19 g, 1.2 mmol) and potassium carbonate (0.28 g, 2 mmol) were added sequentially and the resulting slurry stirred at 50° C. for 4 h. The mixture was cooled to room temperature, diluted with 100 mL CH₂Cl₂, and washed with sat. aq. NaHCO₃, and brine. The aqueous washes were back-extracted with CH₂Cl₂ (2×50 mL). The combined organic extracts were dried over K₂CO₃, filtered and concentrated in vacuo to afford 88a as a yellow solid (0.32 g) which was used without further purification. LCMS (ESI) m/z 353 (M+H)+.

Synthesis of thiazole 1020

[0212] The crude aryl bromide 88a obtained above (0.20 g, 0.56 mmol), boronate ester 81 (0.25 g, 0.66 mmol), and K₂CO₃ (0.14 g, 1.0 mmol) were combined with a 1:1:1 mixture of toluene, ethanol and water (2 mL each). The slurry was degassed by alternately applying high vacuum to the reaction mixture and flushing with dry argon. The reaction vessel was then sealed and heated in an 80° C. oil bath for 14 h. The reaction mixture was cooled to room temperature, diluted with 100 mL 9:1 CH₂Cl₂/MeOH, and washed with water and brine (50 mL each). The aqueous washes were back-extracted once with 50 mL 9:1 CH₂Cl₂/MeOH. The combined organic extracts were dried on K₂CO₃, filtered, and concentrated in vacuo to afford 0.48 g of a brown solid which was purified by silica gel chromatography (25mm×6″ column eluted with 7:3 acetone/hexane) to yield 1020 as an off-white solid (0.17 g, 0.32 mmol). LCMS (ESI) m/z 525 (M+H)+.

Synthesis of thiazole 1021

[0213] Compound 21 was synthesized according to the procedure described above for 1020, using thiourea 88b in place of 88a. The reaction yielded 1021 as a white solid (0.12 g, 0.21 mmol). LCMS (ESI) m/z 561 (M+H)+.

[0214] Scheme 9 illustrates the synthesis of compounds 1022-1025. Azetidine 89 was deprotected and alkylated with chloride 90 to afford amide 91. The amide of 91 was dehydrated with trifluoroacetic anhydride to produce nitrile 1022. The alkylation of 1,2,3-triazole with benzyl chloride 90 gave triazole 1023. Similarly, the alkylation of 5-aminotetrazole with benzyl chloride 90 yielded a mixture of tetrazole 1024 and tetrazole 1025.
Synthesis of chloride 90

[0215] N-[3-(2-fluoro-4′-hydroxymethyl-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 51 (3.0 g, 8.4 mmol) 51 was dissolved in CH₂Cl₂ (20 mL) and Hunig's base (2 mL). Methanesulfonyl chloride (1.4 mL, 12.6 mmol) was added dropwise and the resulting solution stirred at room temperature for 4 h. The mixture was poured into 100 mL sat. aqueous NaHCO₃ and extracted with CH₂Cl₂ (3×50 mL). The combined organic extracts were washed with brine, dried over MgSO₄, filtered, and concentrated to give 3.9 g of an oily yellow solid. The crude material was purified by silica gel chromatography to give chloride 90 as an off-white solid (2.7 g, 7.2 mmol). LCMS (ESI) m/z 377 (M+H)+, 418 (M+CH₃CN +H)+, 440 (M+CH₃CN +Na)+.

Synthesis of amide 91

[0216] A solution of 89 (J. Med. Chem. 1993, 36, 801) (33 mg, 0.17 mmol) in CH₂Cl₂ (1.0 mL) was treated with 4.0 M HCl-dioxane (0.2 mL) and stirred at 23° C. for 2 h. The reaction mixture was evaporated and the residue dissolved in DMF (1.0 mL) and treated with benzyl chloride 90 (63 mg, 0.17 mmol) and Hunig's base (0.17 mL, 1.0 mmol) and stirred at 60° C. for 2 h. The reaction mixture was cooled to 23° C., diluted with H₂O (10 mL) and extracted with CH₂Cl₂ (4×25 mL), dried (Na₂SO₄) and evaporated. The crude residue was purified by preparative TLC (1% NH₄OH-10% MeOH-89% CH₂Cl₂) to afford 91 (36 mg; 50%) as a tan powder. LCMS (ESI) m/z 441.1 (M+H)+.

Synthesis of nitrile 1022

[0217] A solution of 91 (26 mg, 0.06 mmol) in CH₂Cl₂ (1.0 mL) was treated with pyridine (0.02 mL, 0.2 mmol) and trifluoroacetic anhydride (0.035 mL, 0.21 mmol) and stirred at 0° C. for 1 h. The reaction mixture was directly purified by preparative TLC (1% NH₄OH-10% MeOH-89% CH₂Cl₂) to afford 1022 (6.0 mg; 24%) as a tan powder. LCMS (ESI) m/z 423.1 (M+H)+.

Synthesis of triazole 1023

[0218] A solution of 90 (0.19 g, 0.50 mmol) in DMF (2.0 mL) was treated with 1,2,3-triazole (0.058 mL, 1.0 mmol) and cesium carbonate (Cs₂CO₃, 0.33 g, 1.0 mmol) and stirred at 23° C. for 16 h. The reaction mixture was diluted with H₂O (100 mL) and the resulting precipitate was isolated by filtration and purified by preparative TLC (10% MeOH-45% CH₂Cl₂-45% EtOAc) to afford 1023 (39 mg; 19%) as a white powder. LCMS (ESI) m/Z 473.2 (M+CH₃CN +Na)+.

Synthesis of tetrazoles 1024 and 1025

[0219] A solution of 90 (0.19 g, 0.50 mmol) in DMF (2.0 mL) was treated with 5-aminotetrazole (87 mg, 1.0 mmol) and Cs₂CO₃ (0.33 g, 1.0 mmol) and stirred at 23° C. for 12 h. The reaction mixture was diluted with H₂O (100 mL) and the resulting precipitate was isolated by filtration and suspended in 50 mL of a 1:1 mixture of CH₂Cl₂ and MeOH. The insoluble material (55 mg; 26%) was isolated by filtration and assigned the structure of 1024. LCMS (ESI) m/z 426.1 (M+H)+. The soluble material was isolated by evaporation and purified by preparative TLC (1% NH₄OH-10% MeOH-89% CH₂Cl₂) to afford a white powder assigned the structure of 1025 (39 mg; 19%). LCMS (ESI) m/z 489.2 (M+CH₃CN+Na)+.

[0220] Scheme 10 illustrates the synthesis of compounds 1026 and 1027. Azide 53 was converted to triazole 1026, which was then subsequently cyclized to compound 1027.
Synthesis of triazole 1026

[0221] A solution of azide 53 (383 mg, 1.0 mmol) in ethanol (4.0 mL) was treated with cyanoacetamide (101 mg, 1.2 mmol) and a solution of sodium ethoxide (21% wt solution in ethanol, 648 mg, 0.75 mL) at room temperature under N₂. The resulting reaction mixture was stirred for 10 min at room temperature before being warmed up to reflux for 2 h. When TLC showed that the reaction was complete, the reaction mixture was cooled down to room temperature before being treated with H₂O (10 mL). The white precipitate was then collected by filtration, washed with H₂O (2×10mL), and dried in vacuo to afford the desired triazole 1026 (312 mg; 67%) as an off-white powder, which was of sufficient purity to be used directly in subsequent reactions. LCMS (ESI) m/z 468 (M+H)+.

Synthesis of compound 1027

[0222] A suspension of 1026 (165 mg, 0.353 mmol) in anhydrous THF (5 mL) was treated with p-toluenesulfonic acid monohydrate (34.2 mg, 0.18 mmol) and trimethyl orthoformate (374 mg, 0.386 mL, 3.53 mmol) at 25° C. under N₂, and the resulting mixture was warmed up to reflux for 2 h. The solvents were removed in vacuo, and the residue was directly purified by column chromatography (5-10% MeOH/CH₂Cl₂ gradient elution) to afford the desired compound 1027 (42 mg; 25%) as a white powder. LCMS (ESI) m/z 478 (M+H)+.

[0223] A suspension of azide 53 (124 mg, 0.324 mmol) in anhydrous 1,4-dioxane (5.0 mL) was treated with propargyl alcohol (182 mg, 0.19 mL, 3.24 mmol) at 25° C., and the resulting reaction mixture was warmed up to reflux for 12 h. When TLC and LCMS showed the reaction was complete, the reaction mixture was concentrated in vacuo, and the residue was directly purified by column chromatography (0-5% MeOH/CH₂Cl₂ gradient elution) to afford triazole 1028 (93.9 mg; 66%) as a pale-yellow solid. LCMS (ESI) m/z 440 (M+H)+.

[0224] Scheme 11 illustrates the reductive amination chemistry used to synthesize 1029 and 1030.
Synthesis of piperazine 1029

[0225] A solution of aldehyde 92 (made from iodide 50 and 4-formylboronic acid in the same fashion as N-[3-(2-fluoro4′-hydroxymethyl-biphenyl4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide in Example 1) (180 mg, 0.5 mmol) and 2-piperidin4-yl-ethanol (65 mg, 0.065 mL, 0.5 mmol) in anhydrous THF (4.0 mL) and anhydrous DMF (1.0 mL) was treated with sodium triacetoxyborohydride (160 mg, 0.75 mmol) at 25° C., and the resulting mixture was stirred at 25° C. for 12 h. When TLC and LCMS showed the reductive amination reaction was complete, the reaction mixture was concentrated in vacuo. The residue was directly purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford piperazine 1029 (306 mg; 65%) as a colorless oil, which solidified upon standing at room temperature in vacuo. LCMS (ESI) m/z 471 (M+H)+.

Synthesis of piperidine 1030

[0226] A solution of aldehyde 92 (356 mg, 1.0 mmol) and 2-piperazin-1-yl-ethanol (130 mg, 0.123 mL, 1.0 mmol) in anhydrous THF (8.0 mL) and anhydrous DMF (1.6 mL) was treated with sodium triacetoxyborohydride (NaB(OAc)₃H, 318 mg, 1.5 mmol) at 25° C., and the resulting mixture was stirred at 25° C. for 12 h. When TLC and LCMS showed the reductive amination reaction was complete, the reaction mixture was concentrated in vacuo. The residue was directly purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford piperidine 1030 (169 mg; 72%) as a colorless oil, which solidified upon standing at room temperature in vacuo. LCMS (ESI) m/z 470 (M+H)+.

[0227] Scheme 12 depicts the synthesis of tetrazole derivative 1031. D-p-Hydroxyphenyl-glycine was converted to triflate 95, which was subsequently coupled to boronate 81 to afford alcohol 96. Mesylation of 96, followed by displacement with the anion of imidazole and deprotection of the BOC group yielded imidazole derivative 1031.
Synthesis of triflate 95

[0228] A solution of D-p-hydroxyphenylglycine (23.8 g, 142.3 mmol) and potassium carbonate (39.3 g, 284.6 mmol) in THF (200 mL) and H₂O (200 mL) was treated with di-tert-butyl dicarbonate (BOC₂O, 34.14 g, 156.6 mmol) at 25° C., and the resulting reaction mixture was stirred at 25° C. for 2 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was treated with ethyl acetate (200 mL) and H₂O (200 mL). The two layers were separated, and the aqueous solution was extracted with ethyl acetate (200 mL), and the combined organic extracts were discarded. The aqueous layer was then acidified with a 2 N HCl aqueous solution to pH 4 before being extracted with ethyl acetate (2×200 mL). The combined organic extracts were then washed with water (2×100 mL) and saturated aqueous NaCl solution (100 mL), dried over MgSO₄, and concentrated in vacuo. The residual white solids were further dried in vacuo to afford the crude desired acid 93 (36.5 g; 96%), which was of suitable purity for use in subsequent reactions.

[0229] A solution of acid 93 (4.005 g, 15 mmol) in anhydrous THF (20 mL) was treated dropwise with a 1 M solution of BH₃-THF in THF (30 mL, 30 mmol) at 0-5° C., and the resulting reaction mixture was stirred at 0-5° C. for an additional 2 h. When TLC and LCMS showed that the reduction reaction was complete, the reaction mixture was treated with water (50 mL) and ethyl acetate (50 mL). The mixture was then stirred at 25° C. for 30 min before being separated, and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic extracts were then washed with water (2×20 mL) and saturated aqueous NaCl solution (20 mL), dried over MgSO₄, and concentrated in vacuo. The residue was then directly purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford desired alcohol 94 (2.50 g; 66%) as a white powder which was of suitable purity for use in subsequent reactions.

[0230] A suspension alcohol 94 (670 mg, 2.65 mmol) in CH₂Cl₂ (10 mL) was treated with N-phenyltrifluoromethane sulfonamide (947 mg, 2.65 mmol) and triethylamine (535.3 mg, 0.74 mL, 5.3 mmol) at 25° C., and the resulting reaction mixture was stirred at 25° C. for an additional 2 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was quenched with water (10 mL) and CH₂Cl₂ (20 mL). The two layers were then separated, and the aqueous layer was extracted with CH₂Cl₂ (2×20 mL). The combined organic extracts were then washed with water (2×10 mL) and saturated aqueous NaCl solution (10 mL), dried over MgSO₄, and concentrated in vacuo. The residue was then directly purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford triflate 95 (945 mg; 93%) as a white powder which was of suitable purity for use in subsequent reactions.

Synthesis of alcohol 96

[0231] A solution of boronate 81 (2.162 g, 5.72 mmol) and triflate 95 (1.70 g, 4.4 mmol) in toluene (24 mL) was treated with solid potassium carbonate (1.82 g, 13.2 mmol), ethanol (8.0 mL) and H₂O (8.0 mL) at room temperature, and the resulting reaction mixture was degassed three times under a steady stream of argon before being treated with Pd(dppf)₂Cl₂ (184 mg, 0.22 mmol) at room temperature. The reaction mixture was then degassed three times again under a steady stream of argon before being warmed up to reflux for 2 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was cooled down to room temperature before being treated with water (20 mL) and ethyl acetate (20 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic extracts were washed with water (2×20 mL) and saturated aqueous NaCl solution (20 mL), dried over MgSO₄, and concentrated in vacuo. The residue was then purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford (1-{4′[5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-yl}-2-hydroxyethyl)carbamic acid tert-butyl ester 96 (1.543 g; 72%) as yellow oil, which solidified upon standing at room temperature in vacuo.

Synthesis of mesylate 97

[0232] A suspension of alcohol 96 (694 mg, 1.43 mmol) in anhydrous CH₂Cl₂ (10 mL) was treated with diisopropylethylamine (388 mg, 0.522 mL, 2.85 mmol) and methanesulfonyl chloride (196 mg, 0.132 mL, 1.71 mmol) at 0-5° C., and the resulting reaction mixture was stirred at 0-5° C. for an additional 2 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was quenched with water (10 mL). The two layers were separated, and the aqueous layer was extracted with CH₂Cl₂ (2×10 mL). The combined organic extracts were washed with water (2×10 mL) and saturated aqueous NaCl solution (10 mL), dried over MgSO₄, and concentrated in vacuo. The residue was then purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford mesylate 97 (647 mg; 80%) as a pale-yellow solid, which was of suitable purity for use in subsequent reactions.

Synthesis of imidazole 98

[0233] A solution of imidazole (41 mg, 0.6 mmol) in anhydrous THF (3 mL) was treated with NaH (60% oil dispersion, 29 mg, 0.72 mmol) at 0° C., and the resulting mixture was stirred at 0-5° C. for 30 min before a solution of mesylate 97 (170 mg, 0.3 mmol) in anhydrous DMF (3.0 mL) was added. The resulting reaction mixture was then stirred at 0-5° C. for 30 min before being gradually warmed up to room temperature for 12 h. When TLC and LCMS showed that the reaction was complete, the solvents were removed in vacuo, and the residue was directly purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford imidazole 98 (46 mg; 29%) as a yellow solid.

Synthesis of imidazole 1031

[0234] A solution of imidazole 99 (23 mg, 0.043 mmol) in MeOH (1.0 mL) was treated with a solution of 4 N HCl in 1,4-dioxane (3.0 mL), and the resulting reaction mixture was stirred at room temperature for 30 min. When TLC and LCMS showed that the reaction was complete, the solvents were removed in vacuo, and the desired N-{3-[4′-(1-amino-2-imidazol-1-yl-ethyl) 2-fluoro-biphenyl-4-yl]-2-oxo-oxazolidin-5-ylmethyl} acetamide hydrochloride 1031(18.8 mg; 100%) was obtained as a yellow solid. LCMS (ESI) m/z 438 (M+H)+.

[0235] Scheme 13 depicts the synthesis of tetrazole derivatives 1032-1034. Iodide 99 was converted to boronate 100 which served as the coupling partner for bromide 101 to afford tetrazole 102. Deprotection of 102 afforded tetrazole amine 1032, which was subsequently acylated to afford tetrazole 1033 and 1034.
Synthesis of iodide 99

[0236] A solution of known 5-aminomethyl-3-(3-fluoro4-iodo-phenyl)-oxazolidin-2-one (2.02 g, 6.0 mmol; see U.S. Pat. Nos. 5,523,403 and 5,565,571) and potassium carbonate (1.66 g, 12.0 mmol) in THF (20 mL) and H₂O (20 mL) was treated with BOC₂O (1.334 g, 6.12 mmol) at 25° C., and the resulting reaction mixture was stirred at 25° C. for 2 h. When TLC and LCMS showed the reaction was complete, the reaction mixture was treated with ethyl acetate (20 mL) and H₂O (20 mL). The two layers were separated, and the aqueous solution was extracted with ethyl acetate (20 mL), and the combined organic extracts were then washed with water (2×10 mL) and saturated aqueous NaCl solution (10 mL), dried over MgSO₄, and concentrated in vacuo. The residual white solids were further dried in vacuo to afford the crude, desired iodide 99 (2.40 g; 92%), which was of suitable purity for use in subsequent reactions.

Synthesis of boronate 100

[0237] A solution of iodide 99 (1.11 g, 2.55 mmol) in 1,4-dioxane (25 mL) was treated with 4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (489 mg, 0.56 mL, 3.82 mmol) and triethylamine (772 mg, 1.07 mL, 7.65 mmol) at room temperature, and the resulting reaction mixture was degassed three times under a steady stream of argon before being treated with Pd(dppf)₂Cl₂ (107 mg, 0.13 mmol) at room temperature. The reaction mixture was then degassed three times again under a steady stream of argon before being warmed up to reflux for 6 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was cooled down to room temperature before being treated with water (20 mL) and ethyl acetate (20 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic extracts were washed with water (2×20 mL) and saturated aqueous NaCl solution (20 mL), dried over MgSO₄, and concentrated in vacuo. The residual brown oil was then purified by flash column chromatography (10-30% EtOAc-hexanes gradient elution) to afford boronate 100 (646 mg; 58%) as a brown oil, which solidified upon standing at room temperature in vacuo and was of suitable purity for use in subsequent reactions.

Synthesis of bromide 101

[0238] A solution of 4-bromobenzylamine hydrochloride (2.22 g, 10.0 mmol) in acetic acid (30 mL) was treated with triethyl orthoformate (2.964 g, 3.29 mL, 20.0 mmol) and sodium azide (2.30 g, 20.0 mmol) at room temperature, and the resulting reaction mixture was subsequently stirred at reflux for 12 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was cooled down to room temperature, and the cooled reaction mixture was poured into ice-water (100 mL). The precipitate was then collected by filtration, washed with water (2×20 mL), and dried in vacuo to afford crude bromide 101 (460 mg; 19%) as a white solid, which was of suitable purity for use in subsequent reactions.

Synthesis of tetrazole 102

[0239] A solution of boronate 100 (658 mg, 1.5 mmol) and bromide 101 (300 mg, 1.25 mmol) in toluene (9.0 mL) was treated with solid potassium carbonate (621 mg, 4.5 mmol), ethanol (3.0 mL) and H₂O (3.0 mL) at room temperature, and the resulting reaction mixture was degassed three times under a steady stream of argon before being treated with Pd(dppf)₂Cl₂ (52.3 mg, 0.063 mmol) at room temperature. The reaction mixture was then degassed three times again under a steady stream of argon before being warmed up to reflux for 3 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was cooled down to room temperature before being treated with water (10 mL) and ethyl acetate (20 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic extracts were washed with water (2×5 mL) and saturated aqueous NaCl solution (5 mL), dried over MgSO₄, and concentrated in vacuo. The residue was then purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford tetrazole 102 (357 mg; 61%) as a yellow oil, which solidified upon standing at room temperature in vacuo.

Synthesis of tetrazole 1032

[0240] A solution of tetrazole 102 (350 mg, 0.748 mmol) in EtOAc (5.0 mL) was treated with a solution of 4 N HCl in 1,4-dioxane (5.0 mL), and the resulting reaction mixture was stirred at room temperature for 30 min. When TLC and LCMS showed that the reaction was complete, the solvents were removed in vacuo, and the residue was treated with an aqueous sodium bicarbonate solution (10 mL) and EtOAc (15 mL). The mixture was stirred at room temperature for 30 min before the two layers were separated. The aqueous layer was extracted with EtOAc (10 mL), and the combined organic extracts were washed with H₂O (10 mL) and saturated aqueous NaCl solution (10 mL), dried over MgSO₄, and concentrated in vacuo to afford tetrazole amine 1032 (266 mg; 97%) as a pale-yellow solid. LCMS (ESI) m/z 369 (M+H)+.

Synthesis of tetrazole 1033

[0241] A suspension of tetrazole arnine 1032 (74 mg, 0.2 mmol) in anhydrous CH₂Cl₂ (5.0 mL) was treated with diisopropylethylamnine (52 mg, 0.07 mL, 0.4 mmol) and chloroacetyl chloride (34 mg, 0.024 mL, 0.3 mmol) at 0-5° C., and the resulting reaction mixture was stirred at 0-5° C. for 2 h. When TLC and LCMS showed the reaction was complete, the reaction mixture was concentrated in vacuo. The residue was directly purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford tetrazole 1033 (43 mg; 48% yield) as a white solid. LCMS (ESI) m/z 445 (M+H)+.

Synthesis of tetrazole 1034

[0242] A suspension of tetrazole amine 1032 (74 mg, 0.2 mmol) in anhydrous CH₂Cl₂ (5.0 mL) was treated with diisopropylethylamine (52 mg, 0.07 mL, 0.4 mmol) and dichloroacetyl chloride (44 mg, 0.029 mL, 0.3 mmol) at 0-5° C., and the resulting reaction mixture was stirred at 0-5° C. for 2 h. When TLC and LCMS showed the reaction was complete, the reaction mixture was concentrated in vacuo. The residue was directly purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford tetrazole 1034 (41 mg; 43% yield) as a white solid. LCMS (ESI) m/z 479 (M+H)+.

[0243] Scheme 14 depicts the synthesis of tetrazole derivatives 1035 and 1036. Aldehyde 103 was reduced to 104 which was coupled to boronate 81 to yield alcohol 105. Mesylation of 105, followed by displacement with sodium azide, yielded azide 107. Reduction of 107 to amine 108 was followed by conversion to tetrazole 1035. Cycloaddition of azide 107 with trimethylsilylacetylene, followed by desilylation, afforded triazole 1036.
Synthesis of aldehyde 103

[0244] A solution of 2,5-dibromopyridine (25 g, 105.5 mmol) in toluene (1.24 L) was cooled down to −78° C. before being treated dropwise with a 2.5 M solution of n-BuLi in hexane (50.6 mL, 126.6 mmol) at −78° C. under N₂. The resulting reaction mixture was stirred at −78° C. for 1 h before being treated with anhydrous DMF (11.6 g, 12.2 mL, 158.0 mmol) at −78° C. The reaction mixture was stirred at −78° C. for an additional 1 h before being gradually warmed up to room temperature for 6 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was quenched with water (200 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic extracts were then washed with H₂O (2×200 mL), and saturated aqueous NaCl solution (100 mL), and dried over MgSO₄. The solvents were then removed in vacuo, and the residual pale-yellow oil was purified by flash column chromatography (0-15% EtOAc-hexane gradient elution) to afford aldehyde 103 (10.2 g; 52%) as a pale-yellow solid.

Synthesis of bromide 104

[0245] A solution aldehyde 103 (4.91 g, 26.4 mmol) in methanol (120 mL) was treated with sodium borohydride (1.18 g, 31.7 mmol) at 0-5° C., and the resulting reaction mixture was stirred at 0-5° C. for an additional 1 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was quenched with water (20 mL). The solvents were then removed in vacuo, and the residue was directly purified by flash column chromatography (5-25% EtOAc-hexane gradient elution) to afford bromide 104 (4.23 g; 85%) as a white solid.

Synthesis of alcohol 105

[0246] A solution of boronate 81 (11.05 g, 29.2 mmol) and bromide 104 (4.227 g, 22.5 mmol) in toluene (150 mL) was treated with solid potassium carbonate (9.315 g, 67.5 mmol), ethanol (50 mL) and H₂O (50 mL) at room temperature, and the resulting reaction mixture was degassed three times under a steady stream of argon before being treated with Pd(dppf)₂Cl₂ (564 mg, 0.675) at room temperature. The reaction mixture was then degassed three times again under a steady stream of argon before being warmed up to reflux for 1 h. When LCMS showed that the reaction was complete, the reaction mixture was cooled down to room temperature before being treated with water (200 mL) and ethyl acetate (100 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with water (2×50 mL) and saturated aqueous NaCl solution (50 mL), dried over MgSO₄, and concentrated in vacuo. The residue was then purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford alcohol 105 (6.16 g; 76%) as a grey solid.

Synthesis of azide 107

[0247] A suspension of alcohol 105 (2.15 g, 6.0 mmol) in CH₂Cl₂ (25 mL) was treated with diisopropylethylamine (1.551 g, 2.10 mL, 12.0 mmol) and methanesulfonyl chloride (756 mg, 0.511 mL, 6.6 mmol) at 0-5° C., and the resulting reaction mixture was stirred at 0-5° C. for an additional 2 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was treated with water (20 mL) and CH₂Cl₂ (40 mL). The two layers were separated, and the aqueous layer was extracted with CH₂Cl₂ (20 mL). The combined organic extracts were washed with water (20 mL) and saturated aqueous NaCl solution (20 mL), dried over MgSO₄, and concentrated in vacuo. The residue was then purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford mesylate 106 (2.47 g; 94%) as a yellow solid.

[0248] A solution of mesylate 106 (874 mg, 2.0 mmol) in DMF (8.0 mL) was treated with sodium azide (260 mg, 4.0 mmol) at room temperature, and the resulting reaction mixture was warmed up to 40-45° C. for 3 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was treated with water (20 mL), and the precipitate was collected by filtration, washed with water (2×10 mL), and dried in vacuo to afford crude azide 107 (699 mg; 91%) as a grey solid, which was of suitable purity for use in subsequent reactions.

Synthesis of amine 108

[0249] A suspension of azide 107 (2.611 g, 6.8 mmol) in THF (25 mL) was treated with water (0.13 mL, 68 mmol) and triphenylphosphine (PPh₃, 2.14 g, 8.2 mmol) at room temperature, and the resulting reaction mixture was subsequently stirred at room temperature for 12 h. When TLC and LCMS showed that the reaction was complete, the solvents were removed in vacuo, and the residue was directly purified by flash column chromatography (0-15% MeOH-CH₂Cl₂ gradient elution) to afford amine 108 (2.233 g; 92%) as a yellow solid.

Synthesis of tetrazole 1035

[0250] A solution of amine 108 (90 mg, 0.25 mmol) in acetic acid (3.0 mL) was treated with triethyl orthoformate (0.1 mL) and sodium azide (40 mg) at room temperature, and the resulting reaction was subsequently stirred at reflux for 4 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was cooled down to room temperature and concentrated in vacuo. The residue was then directly purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford tetrazole 1035 (43 mg; 36%) as a white solid. LCMS (ESI) m/z 412 (M+H)+.

Synthesis of triazole 1036

[0251] A solution of azide 107 (142 mg, 0.37 mmol) in DMF (5 mL) was treated with thimethylsilyl acetylene (0.5 mL) at room temperature, and the resulting reaction mixture was subsequently stirred at 70-80° C. for 12 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was cooled down to room temperature before being concentrated in vacuo. The residue was then directly purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford triazole 109 (152 mg; 85%) as a pale-yellow oil, which was directly used in the subsequent reaction.

[0252] A solution of triazole 109 (152 mg, 0.315 mmol) in THF (10 mL) was treated with a 1 N solution of tetrabutylammonium fluoride in THF (2.0 mL) at 0-5° C., and the resulting reaction mixture was stirred at 0-5° C. for 1 h before being gradually warmed up to room temperature for 10 h. When TLC and LCMS showed that the reaction was complete, the reaction mixture was cooled down to room temperature before being concentrated in vacuo. The residue was then directly purified by flash column chromatography (0-5% MeOH-CH₂Cl₂ gradient elution) to afford triazole 1036 (67 mg; 52%) as a pale-yellow oil, which solidified upon standing at room temperature in vacuo. LCMS (ESI) m/z 411 (M+H)+