Pharmaceutical composition comprising a dual antagonist against PGD₂/TXA₂ receptors having a [2.2.1] or [3.1.1] bicyclic skeleton

[0001] This is a national stage application under 35 USC § 371 of PCT/JP00/01223, filed Mar. 2, 2000.

[0002] The present invention relates to a compound having a [2.2.1] or [3.1.1] bicyclic skeleton and a pharmaceutical composition comprising the same having a dual antagonistic activity against PGD₂/TXA₂ receptors.

[0003] Some compounds similar to those of the present invention having a [2.2.1] or [3.1.1] bicyclic skeleton have been described as thromboxane A₂ (TXA₂) antagonists in the Japanese Patent Publication (Kokoku) No. 53295/1991. TXA₂ is known to possess various activities such as platelet aggregation, thrombogenesis, contraction of airway smooth muscle, advance of respiratory anaphylaxis and the like. The TXA₂ antagonists have, therefore, been considered to be useful as anti-thrombotic agents, anti-vasoconstrictor, anti-respiratory contractile agents as well as medicines for treating myocardial infarction or asthma. The TXA₂ antagonists can be used for treating or improving conditions of diseases such as arteriosclerosis, myocardial infarction, acute myocardial ischemia angina, cardiovascular shock or preventing unexpected death and the like.

[0004] Further, other compounds similar to those of the present invention having a [2.2.1] or [3.1.1] bicyclic skeleton have been described as prostaglandin D₂ (PGD₂) antagonists in WO97/00853. PGD₂ is a prostanoid released from mast cells in which it is produced through PGG₂ and PGH₂ from arachidonic acid by the action of cyclooxygenase activated by immunological or unimmunological stimulation.

[0005] PGD₂ can cause strong contraction of smooth muscle of bronchus to lead to bronchial asthma, and dilate the peripheral vessels to cause an anaphylactic shook in a systemic allergic state.

[0006] Accordingly, PGD₂ antagonists are useful for the improvement of conditions caused by excessive production of PGD₂, particularly as medicines for treating diseases involved with mast cell dysfunction, for example, systemic mastocytosis and disorder of systemic mast cell activation as well as tracheal contraction, allergic rhinitis, allergic conjunctivitis, urticaria, itching, atopic dermatitis, alimentary allergy, ischemic reperfusion injury, cerebrovascular disorder, and inflammation.

[0007] As shown above, PGD₂ receptor antagonists have a quite different character from that of TXA₂ receptor antagonists in the site and mechanism of action and indications thereof.

[0008] On the other hand, a compound having a dual antagonistic activity against both a TXA₂ receptor and a PGD₂ receptor can be useful as therapeutic agents for various diseases caused by TXA₂ or PGD₂.

[0009] For example, in the case of bronchial asthma, it is known that TXA₂ cause potent tracheal contraction and respiratory anaphylaxis and PGD₂ effects infiltration of eosionophils. From these comprehension, TXA₂ and PGD₂ are thought to be one of causative substances of the pathopoiesis and advance of asthma, thus the dual antagonistic compounds are expected to be more potent agents for treating asthma than ever known antagonists.

[0010] Further, in the case of allergic rhinitis, it is recognized that TXA₂ and PGD₂ cause the swelling of nasal mucosa through the aggravation of vascular permeability, and PGD₂ induces the nasal blockage through the enlargement of vascular volume. Therefore, the dual antagonistic compounds are expected to be more potent agents for treating nasal blockage than ever known antagonists.

[0011] These diseases and condition thereof might be treated by administering both a TXA₂ receptor antagonist and a PGD₂ receptor antagonist at the same time, for example, in combination therapy or as a mixture thereof. But the administration of two or more agents often causes some problems due to the difference of their metabolic rate. For example, when the antagonists are different from each other in the time to reach a maximum blood concentration or the duration of action, they do not always efficiently exhibit each receptor antagonistic effect at the same time, failing to give a desired additive or synergic effect.

[0012] It has therefore been desired to develop medicines having a dual antagonistic activity against TXA₂/PGD₂ receptors, which exhibit new excellent therapeutic effects and can be used for many indications.

[0013] The present inventors have studied intensively to develop a pharmaceutical composition having a dual antagonistic activity against TXA₂/PGD₂ receptors and found out new compounds and pharmaceutical compositions comprising them.

[0014] The present invention provides:

[0015] (1) a pharmaceutical composition having a dual antagonistic activity against PGD₂/TXA2 receptors which comprises a compound of the formula (I):

[0016]

[0017] R¹ is —CH₂—CH═CH—CH₂—CH₂—CH₂—COOR² or —CH═CH—CH₂—CH₂—CH₂—COOR₂;

[0018] R2 is hydrogen or alkyl;

[0019] m is 0 or 1;

[0020] p is 0 or 1, provided that when p=0, X¹ is not bonded to X³ via X⁴;

[0021] X¹ and X³ are independently optionally substituted aryl or optionally substituted heteroaryl;

[0022] X² is a single bond, —CH₂—, —CH₂—CH₂—, —C(═O)—, —O—, —S—, —SO—, —SO₂—, —NH—, —N(CH₃)—, —C(═N—O—CH₃)—, —N═N—, —CH═CH—, —(C═O)—NH—, —NH—(C═O)—, —CH₂NH—, —NH—CH₂—, —CH₂—O—, —O—CH₂—, —CH₂—S—, —S—CH₂—, —CH₂—SO₂—, —SO₂—CH₂—, —SO₂—NH— or —NH—SO₂—;

[0023] X⁴ is —CH₂—, —CH₂—CH₂—, —C(═O)—, —SO—, —SO₂—, —(C═O)—NH—, —NH—(C═O)—, —CH₂NH—, —NH—CH₂—, —CH₂—O—, —O—CH₂—, —CH₂—S—, —S—CH₂—, —CH₂—SO₂—, —SO₂—CH₂—, —SO₂—NH— or —NH—SO₂—, a prodrug, a pharmaceutically acceptable salt or a hydrate thereof,

[0024] (2) the pharmaceutical composition having a dual antagonistic activity against PGD₂/TXA₂ receptors according to the above (1) wherein at least one of X¹ and X³ is optionally substituted heteroaryl,

[0025] (3) the pharmaceutical composition having a dual antagonistic activity against PGD₂/TXA₂ receptors according to the above (1) or (2) wherein R¹ is —CH₂—CH═CH—CH₂—CH₂—CH₂—COOH, m is 0 and p is 0,

[0026] (4) the pharmaceutical composition having a dual antagonistic activity against PGD₂/TXA₂ receptors according to any one of the above (1) to (3) which is used for asthma,

[0027] (5) the pharmaceutical composition having a dual antagonistic activity against PGD₂/TXA₂ receptors according to any one of the above (1) to (3) which is used for nasal blockage,

[0028] (6) use of the compound according to any one of the above (1) to (3) for manufacturing a pharmaceutical composition for asthma or nasal blockage,

[0029] (7) a method for treating asthma or nasal blockage which comprises administering the compound according to any one of the above (1) to (3),

[0030] (8) a compound of the formula (I):

[0031]

[0032] R¹ is —CH₂—CH═CH—CH₂—CH₂—CH₂—COOR₂ or —CH═CH—CH₂—CH₂—CH₂—COOR₂;

[0033] R² is hydrogen or alkyl;

[0034] m is 0 or 1;

[0035] p is 0 or 1, provided that when p=0, X¹ is not bonded to X³ via X⁴;

[0036] X¹ and X³ are independently optionally substituted aryl or optionally substituted heteroaryl;

[0037] X² is a single bond, —CH₂—, —CH₂—CH₂—, —C(═O)—, —O—, —S—, —SO—, —SO₂—, —NH—, N(CH₃)—, —C(═N—O—CH₃)—, —N═N—, —CH═CH—, —(C═O)—NH—, —NH—(C═O)—, —CH₂—NH—, —NH—CH₂—, —CH₂—O—, —O—CH₂—, —CH₂—S—, —S—CH₂—, —CH₂—SO₂—, —SO₂—CH₂—, —SO₂—NH— or —NH—SO₂—;

[0038] X⁴ is —CH₂—, —CH₂—CH₂—, —C(═O)—, —SO—, —SO₂—, —(C═O)—NH—, —NH—(C═O)—, —CH₂—NH—, —NH—CH₂—, —CH₂—O—, —O—CH₂—, —CH₂—S—, —S—CH₂—, —CH₂—SO₂—, —SO₂—CH₂—, —SO₂—NH—, or —NH—SO₂—;

[0039] provided that when

[0040]
a compound wherein R¹ is —CH₂—CH═CH—CH₂—CH₂—CH₂—COOR², R² is hydrogen or methyl, m is 0, p is 0, X¹ is phenyl optionally substituted with methoxy, X² is a bond, —O—, —CH₂—, —C(═O)—NH—, —S— or —N═N—, and X³ is phenyl optionally substituted with hydroxy, acetoxy or methoxy, and a compound wherein R¹ is —CH₂—CH═CH—CH₂—CH₂—CH₂—COOH, m is 1, p is 0, X¹ is phenyl, X² is —N═N—, and X³ is phenyl, are excluded, and when

[0041]
R¹ is —CH₂—CH═CH₂—CH₂—CH₂—COOR², R² is hydrogen or methyl, m is 0, and p is 0, a compound wherein X¹ is phenyl optionally substituted with methyl or methoxy, X² is a single bond, —CH₂—CH₂—, —C(═O)—, —NH—, —O—, —S—, —SO—, —SO₂—, —CH═CH—, —N═N—, —C(═O)—NH— or —NH—C(═O)—, and X³ is phenyl optionally substituted with methyl, hydroxy, acetoxy, methoxy, ethoxy, isopropoxy, dimethylamino, hydroxymethyl, methoxymethyl or carboxy, a compound wherein X¹ is phenyl, X² is a single bond, —CH₂— or —CH═CH—, and X³ is imidazolyl, thienyl, pyridyl or tetrazolyl optionally substituted with methyl or phenyl, and a compound wherein X¹ is benzothienyl, isoxazolyl or thienyl optionally substituted with methyl, X² is a single bond or —S—, and X³ is phenyl optionally substituted with methoxy or methyl, are excluded, a prodrug, a pharmaceutically acceptable salt, a hydrate thereof,

[0042] (9) the compound according to the above (8) wherein at least one of X¹ and X³ is optionally substituted heteroaryl, the prodrug, the pharmaceutically acceptable salt, the hydrate thereof,

[0043] (10) the compound according to the above (8) wherein X¹ and X³ each is independently optionally substituted heteroaryl, the prodrug, the pharmaceutically acceptable salt, the hydrate thereof,

[0044] (11) the compound according to the above (8) wherein at least one of X¹ and X³ is optionally substituted thienyl or optionally substituted benzothienyl, the prodrug, the pharmaceutically acceptable salt, the hydrate thereof,

[0045] (12) the compound according to any one of the above (8) to (11) wherein X² is a single bond, —CH₂—, —S—, —SO₂—, —CH₂—O—, —O—CH₂—, —CH₂—S— or —S—CH₂—, the prodrug, the pharmaceutically acceptable salt, the hydrate thereof,

[0046] (13) the compound according to any one of the above (8) to (12) wherein R¹ is —CH₂—CH═CH—CH₂—CH₂—CH₂—COOH, m is 0, and p is 0, the prodrug, the pharmaceutically acceptable salt, the hydrate thereof,

[0047] (14) a pharmaceutical composition which comprises a compound according to any one of the above (8) to (13),

[0048] (15) a pharmaceutical composition having a dual antagonistic activity against PGD₂/TXA₂ receptors which comprises a compound according to any one of the above (8) to (13),

[0049] (16) the pharmaceutical composition according to the above (14) or (15), which is used for asthma, and

[0050] (17) the pharmaceutical composition according to the above (14) or (15), which is used for nasal blockage.

[0051] A compound of the present invention is characterized in that

[0052] (A) a bicyclic ring represented by the Y ring of the above formula (I) is [2.2.1] or [3.1.1] skeleton,

[0053] (B) an ω chain attached to the bicyclic ring, a group represented by the formula:

[0054]
of the above formula (I), includes —NH—CO—, and X¹ and X³ each is independently optionally substituted aryl or optionally substituted heteroaryl,

[0055] (C) X¹ and X³ bond via X², and the like

[0056] A more preferred embodiment is a compound of the formula (I) wherein

[0057] (1) at least one of X¹ and X³ is optionally substituted heteroaryl,

[0058] (2) X¹ and X³ each is independently optionally substituted heteroaryl,

[0059] (3) at least one of X¹ and X³ is optionally substituted thienyl or optionally substituted benzothienyl,

[0060] (4) R¹ is —CH₂—CH═CH—CH₂—CH₂—CH₂—COOH, m is 0 and p is 0,

[0061] (5) X² is a bond, —CH₂—, —S—, —SO₂—, —CH₂—O—, —O—CH₂—, —CH₂—S— or —S—CH₂—,

[0062] (6) R¹ is —CH═CH—CH₂—CH₂—CH₂—COOH and m is 1, or

[0063] (7) p is 0.

[0064] The term “heteroaryl” includes a 5- to 7-membered aromatic heterocycle containing one or more oxygen atom, sulfur atom and/or nitrogen atom in the ring, or such an aromatic heterocycle as fused with one or more carbocycle or other aromatic heterocycle, which has a bond at any substitutable. Any one of aromatic heterocycle and aromatic carbocycle may have a bond. “Heteroaryl” may have a bond at a nitrogen atom as well as a carbon atom of aromatic heterocycle or aromatic carbocycle. Examples of “heteroaryl” include pyrrolyl (e.g., 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl), pyridyl (e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl), pyrazolyl (e.g., 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl), imidazolyl (e.g., 1-imidazolyl, 2-imidazolyl, 4-imidazolyl), pyrimidinyl (e.g., 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl), pyrazinyl (e.g., 2-pyrazinyl), indolyl (e.g., 1-indolyl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl), carbazolyl (e.g., 1-carbazolyl, 2-carbazolyl, 3-carbazolyl, 4-carbazolyl, 9-carbazolyl), benzimidazolyl (e.g., 1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl), indazolyl (e.g., 1-indazolyl, 2-indazolyl, 3-indazolyl, 4-indazolyl, 5-indazolyl, 6-indazolyl, 7-indazolyl), quinolyl (e.g., 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl), isoquinolyl (e.g., 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl), furyl (e.g., 2-furyl, 3-furyl), benzofuryl (e.g., 2-benzofuryl, 3-benzofuryl, 4-benzofuryl, 5-benzofuryl, 6-benzofuryl, 7-benzofuryl), thienyl (e.g., 2-thienyl, 3-thienyl), benzothienyl (e.g., benzo[b]thiophen-2-yl, benzo[b]thiophen-3-yl, benzo[b]thiophen-4-yl, benzo[b]thiophen-5-yl, benzo[b]thiophen-6-yl, benzo[b]thiophen-7-yl), dibenzothienyl (e.g., 2-dibenzothienyl, 3-dibenzothienyl), dibenzofuryl (e.g., 2-dibenzofuryl, 3-dibenzofuryl), naphthothienyl (e.g., naphtho[2,3-b]thiophen-2-yl, naphtho [2,3-b]thiophen-3-yl, naphtho[1.2-b]thiophen-2-yl, naphtho[1.2-b]thiophen-3-yl), oxazolyl (e.g., 2-oxazolyl, 4-oxazolyl, 5-oxazolyl), isoxazolyl (e.g., 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl), thiazolyl (e.g., 2-thiazolyl, 4-thiazolyl, 5-thiazolyl), isothiazolyl (e.g., 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl), imidazothiazolyl (e.g., imidazo[2.1-b]thiazol-2-yl, imidazo[2.1-b]thiazol-3-yl), benzoisoxazolyl (e.g., benzo[d]isoxazol-3-yl), benzothiazolyl (e.g., benzo[d]thiazol-2-yl) or the like.

[0065] “Aromatic carbocycle or other aromatic heterocycle” which may fuse the above “heteroaryl” includes 5- to 7-membered aromatic cycle which may contains one or more oxygen atom, sulfur atom and/or nitrogen atom in the ring, or such a aromatic ring as fused with one or more other aromatic rings.

[0066] “Aryl” includes mono aromatic carbocyclyl (e.g., phenyl) or fused aromatic heterocyclyl (e.g., 1-naphthyl, 2-naphthyl, 1-anthryl, 9-anthryl, 1-phenanthryl, 10-phenanthryl).

[0067] “Aryl” or “heteroaryl” may be fused 4- to 7-membered cycloalkane or 4- to 7-membered non-aromatic heterocycle. Examples of cycloalkane include cyclobutane, cyclopentane, cyclohexane, cycloheptane. Examples of nonaromatic heterocycle includes pyrrolidine, piperazine, oxorane, 1,3-dioxorane, 1,4-dioxane, thiorane, or the like. “cycloalkane” or “non-aromatic heterocycle” may be fused with aromatic carbocycle or aromatic heterocycle. Examples of aryl or heteroaryl fused with 4- to 7-membered cycloalkane or 4- to 7-membered non-aromatic heterocycle are illustrated below.

[0068]

[0069] Examples of the substituent on “optionally substituted aryl” or “optionally substituted heteroaryl” include a group of the formula: —Z¹–Z² wherein Z¹ is a single bond, —O—, —S—, —NH—, —NH—C(═O)—, —NH—C(═O)—O—, —NH—SO₂—, —C(═O)—, —O—C(═O)—, —C(═O)—O—, or —SO₂-; and Z² is alkyl, haloalkyl, alkenyl, alkynyl, aryl optionally substituted alkyl or halogen, heteroaryl optionally substituted with alkyl or halogen, arylalkyl optionally substituted with alkyl or halogen, heteroarylalkyl optionally substituted with alkyl or halogen, carboxy, halogen (F, Cl, Br, I), hydroxyalkyl, hydroxy, nitro, cyano, mercapto, thioformyl, thioacetyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfamoyl, sulfoamino, optionally substituted amino, optionally substituted aminoalkyl, hydroxyamino, carbamoyl, hydorazino. One to three substituents may be at any suitable position on the above aryl or heteroaryl.

[0070] “Alkyl” includes a straight or branched C1 to C8 alkyl group or a C3 to C8 cycloalkyl group , for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, n-octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or the like.

[0071] “Haloalkyl” includes a straight or branched C1 to C8 alkyl or C3 to C8 cycloalkyl group substituted with one or more halogen, for example, chloromethyl, fluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 1,1-difluoroethyl, trichloromethyl, 2,2,2-trichloroethyl, 1,1-dichloroethyl or the like.

[0072] “Alkenyl” includes a straight or branched C2 to C8 alkenyl or C3 to C8 cycloalkenyl group having one or more double bonds, for example, vinyl, 1-propenyl, 2-propenyl, isopropenyl, 2-cyclobuten-1-yl, 2-cyclopenten-1-yl, 3-cyclopenten-1-yl, 2-cyclohexen-1-yl or the like.

[0073] “Alkynyl” includes a straight or branched C2 to C8 alkynyl or C3 to C8 cycloalkynl group having one or more triple bonds, for example, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl or the like.

[0074] “Halogen” means fluoro, chloro, bromo, iodo.

[0075] “Alkyl”, “aryl” and “heteroaryl” used in the term “arylalkyl” or “heteroarylalkyl” have the same meaning of the above “alkyl”, “aryl” and “heteroaryl”.

[0076] “Hydroxy alkyl” includes the above “alkyl” substituted with one or two hydroxy, for example, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, 1,2-dihydroxy-n-propyl or the like.

[0077] Examples of the substituent of “optionally substituted amino” or “optionally substituted amino alkyl” include the above “alkyl”, the above “arylalkyl”, the above “aryl”, the above “heteroaryl”, the above “heteroarylalkyl” or the like. They may be mono- or di-substituted with these substituents. When the substituent is alkyl, alkyl may form a ring together with a nitrogen atom of an amino group.

[0078] Example of “optionally substituted amino” includes amino, dimethylamino, methylethylamino, diethylamino, pyrrolidino, piperidino, phenylmethylamino, isopropylamino, diisopropylamino or the like.

[0079] Examples of “optionally substituted aminoalkyl” include dimethylaminomethyl, methylethylaminomethyl, diethylaminomethyl, pyrrolidinomethyl, piperidinomethyl, phenylmethylaminomethyl, isopropylaminomethyl, diisopropylaminomethyl or the like.

[0080] “A pharmaceutical composition having a dual antagonistic activity against PGD₂/TXA₂ receptors” means a pharmaceutical composition comprising a compound having at least one compound of the formula (I) having an antagonistic activity against both a PGD₂ receptor and a TXA₂ receptor.

[0081] The present invention includes a method for treating asthma or nasal blockage which comprises administering a compound of the formula (I) and use of a compound of the formula (I) for manufacturing a medicine for asthma or nasal blockage.

[0082] A compound of the present invention can be any of the following stereo isomers of [2.2.1] and [3.1.1] bicyclic skeleton.

[0083]

[0084] In these stereo isomers, the most preferable is a compound having the skeleton of the formula:

[0085]

[0086] “α chain” means a group represented by the formula: —R¹, and “ω chain” means a group represented by the formula:

[0087]

[0088] The present invention includes all stereo isomers of them and the optional mixtures thereof. Namely, the bond binding to the bicyclic ring is in R configuration or S configuration, and all of the stereo isomers (diastereomer, epimer, enantiomer and the like), racemates, and optional mixture thereof are included in the present invention.

[0089] Moreover, the α chain of the compound of the present invention can be in Z configuration or E configuration, thus a compound having any of the configurations and the mixture thereof are included in the present invention.

[0090] A prodrug of a compound of the formula (I) is a derivative of the compound of the present invention having a group which can be decomposed chemically or metabolically, and such prodrug is converted to a pharmaceutically active compound of the present invention by means of solvolysis or by placing the compound in vivo under a physiological condition. Method for the selection and process of an appropriate prodrug derivative are described in the literature such as Design of Prodrugs, Elsevier, Amsterdam 1985.

[0091] When the compound of the formula (I) has a carboxyl group, an ester derivative prepared by reacting a basal acid compound with a suitable alcohol or an amide derivative prepared by reacting a basal acid compound with a suitable amine is exemplified as a prodrug. A particularly preferred ester derivative as an prodrug is an optionally substituted alkyl ester derivative (e.g., methyl ester, ethyl ester, n-propyl ester, isopropyl ester, n-butyl ester, isobutyl ester, tert-butyl ester, morpholinoethyl ester), an arylalkyl ester derivative (e.g., benzyl ester, phenethyl ester, benzhydryl ester), or the like. A particularly preferred amide derivative as a prodrug is alkyl amide derivative (e.g., N-methyl amide, N-ethyl amide, N-(n-propyl)amide, N-isopropyl amide, N-(n-butyl)amide, N-isobutyl amide, N-(tert-butyl)amide), aryl alkyl amide (e.g., N-benzyl amide, N-phenethyl amide, benzhydryl amide), or the like.

[0092] When the compound of the formula (I) has a hydroxy group, an acyloxy derivative prepared by reacting with a suitable acyl halide (e.g., acid chloride, halogenated acid) or a suitable acid anhydride (e.g., mixed acid anhydride) is exemplified as a prodrug. A particularly preferred acyloxy derivative as a prodrug is a derivative substituted with optionally substituted alkylcarbonyloxy (e.g., —OCOC₂H₅, —OCO(tert-Bu), —OCOC₁₅H₃₁, —OCOCH₂CH₂COON_a, —OCOCH(NH₂)CH₃, —OCOCH₂N(CH₃)₂—), optionally substituted arylcarbonyloxy (e.g., —OCO(m—COON_a—Ph) or the like.

[0093] When the compound of the formula (I) has an amino group, an amide derivative prepared by reacting with a suitable acid halide or a suitable acid anhydride is exemplified as a prodrug. A particularly preferred amide derivative as a prodrug is a derivative substituted with optionally substituted alkylcarbonyl (e.g., —NHCO(CH₂)₂₀CH_3, —NHCOCH(NH₂)CH₃) or the like.

[0094] Examples of a salt of the compound of the formula (I) or its prodrug include alkali metal salts such as lithium salts, sodium salts or potassium salts, alkaline-earth metal salts such as calcium salts, salts with organic bases such as tromethamine, trimethylamine, triethylamine, 2-aminobutane, tert-butylamine, diisopropylethylamine, n-butylmethylamine, cyclohexylamine, dicyclohexylamine, N-isopropylcyclohexylamine, furfurylamine, benzylamine, methylbenzylamine, dibenzylamine, N,N-dimethylbenzylamine, 2-chlorobenzylamine, 4-methoxybenzylamine, 1-naphthylene methylamine, diphenylbenzylamine, triphenylamine, 1-naphthylamine, 1-aminoanthorathene, 2-aminoanthorathene, dehydroabiethylamine, N-methylmorpholine, pyridine), basic amino acid salts such as arginine salts or lysine salts.

[0095] A hydrate means a hydrate of the compound of the formula (I), its prodrug or its pharmaceutically acceptable salt, for example, monohydrate, dihydrate or the like.

[0096] General processes for the preparation of the compounds of the formula (I) are illustrated as follows.

[0097]

[0098] R¹ is —CH₂—CH═CH—CH₂—CH₂—CH₂—COOR2 or —CH═CH—CH₂—CH₂—CH₂—COOR²;

[0099] R² is hydrogen or alkyl;

[0100] m is 0 or 1;

[0101] p is 0 or 1, provided that when p is 0, X¹ is not bonded to X³ via X⁴;

[0102] X¹ and X³ each is independently optionally substituted aryl or optionally substituted heteroaryl;

[0103] X² is a bond, —CH₂—, —CH₂—CH₂—, —C(═O)—, —O—, —S—, —SO—, —SO₂—, —NH—, —N(CH₃)—, —C(═N—O—CH₃)—, —N═N—, —CH═CH—, —(C═O)—NH—, —NH—(C═O)—, —CH₂—NH—, —NH—CH₂—, —CH₂—O—, —O—CH₂—, —CH₂—S—, —S—CH₂—, —CH₂—SO₂—, —SO₂—CH₂—, —SO₂—NH— or —NH—SO₂—;

[0104] X⁴ is —CH₂—, —CH₂—CH₂—, —C(═O)—, —SO—, —SO₂—, —(C═O)—NH—, —NH—(C═O)—, —CH₂—NH—, —NH—CH₂—, —CH₂—O—, —O—CH₂—, —CH₂—S—, —S—CH₂—, —CH₂—SO₂—, —SO₂—CH₂—, —SO₂—NH— or —NH—SO₂—.

[0105] As shown in the above process, the compound of the formula (I) can be prepared by reacting a carboxylic acid of the formula (M-2) or its reactive derivative with an amino compound of the formula (M-1).

[0106] In this process, the starting compound (M-1) wherein R¹ is —CH₂—CH═CH—CH₂—CH₂—CH₂—COOMe, m is 0, Y is [2.2.1]bicyclic skeleton, 7-(3-amino-bicyclo[2.2.1]hept-2-yl)-5-heptenoic acid methyl ester is described in the Japanese Patent Publication (Kokoku) No. 79060/1993. The other starting compounds can be prepared in accordance with methods as described in the above publication.

[0107] When p is 0, the carboxylic acid of the formula (M-2) can be prepared by reacting a carboxylic acid having X¹ or its reactive derivative with a compound having X³. A person ordinary skilled in the art can carry out such a reaction by selecting the kinds of reactions and their conditions depending on the kind of X².

[0108] The reactive derivatives of carboxylic acid of the formula (M-2) mean the corresponding acid halides (e.g., chloride, bromide, iodide), acid anhydrides (e.g., mixed acid anhydride with formic acid or acetic acid), active esters (e.g., succinimide ester), and the like, and include acylating agents used for the usual acylation of amino group.

[0109] For example, an acid halide is obtained by reacting the compound (M2) with a thionyl halide (e.g., thionyl chloride), phosphorous halide (e.g., phosphorous trichloride, phosphorous pentachloride), oxalyl halide (e.g., oxalyl chloride), and the like, in accordance with known methods as described in the literatures (e.g., Shin-Jikken-Kagaku-Koza, Vol. 14, 1787 (1978); Synthesis 852–854 (1986); Shin-Jikken-Kagaku-Koza Vol. 22, 115 (1992)).

[0110] The reaction can be conducted under a condition generally used for the acylation of amino group. For example, in the case of condensation with the acid halide, the reaction is carried out in a solvent such as an ether solvent (e.g., diethyl ether, tetrahydrofuran, dioxane), benzene solvent (e.g., benzene, toluene, xylene), halogenated hydrocarbon solvent (e.g., dichloromethane, dichloroethane, chloroform) as well as ethyl acetate, dimethylformamide, dimethyl sulfoxide, acetonitrile, or the like, if necessary, in the presence of a base (e.g., organic base such as triethylamine, pyridine, N,N-dimethylaminopyridine, N-methylmorpholine; inorganic base such as sodium hydroxide, potassium hydroxide, potassium carbonate, or the like) under cooling, at room temperature, or under heating, preferably at a temperature ranging from −20° C. to ice-cooling temperature, or from a room temperature to a refluxing temperature of the reaction system, for a period of several min to several hr, preferably for 0.5 hr to 24 hr, particularly, for 1 hr to 12 hr.

[0111] In the case of using the carboxylic acid (M-2) in a free form without converting into the reactive derivatives, the reaction is conducted in the presence of a condensing agent (e.g., dicyclohexylcarbodiimide (DCC), 1-ethyl-3-(3-methylaminopropyl)carbodiimide, N,N′-carbonyldiimidazole) usually used in the condensation reaction of amine and carboxylic acid.

[0112] When “optionally substituted aryl” or “optionally substituted heteroaryl” in X¹ or X³ of the compound of the formula (M-2) is substituted with a hydroxy group or an amino group, such a compound can be used after protection by acetyl group or the like in accordance with the well known method.

[0113] In the reaction of the other reactive derivatives or free acid (M-2) with the amine (M-1), the reaction conditions are determined according to the property of each reactive derivative or free acid, in accordance with a known method. The reaction product can be purified in accordance with a conventional purification, such as the extraction with a solvent, chromatography, recrystallization, and the like.

[0114] When p is O, a group of the formula: —NHCO—X¹—X²—X³ of the compound (I) can be introduced by reacting a carboxylic acid of the formula: X³—X²—X¹—COOH (M-2) or its reactive derivative with amine (M-1), or by reacting a carboxylic acid having X¹ or its reactive derivatives with amine (M-1) and reacting the obtained compound with a compound having X³.

[0115] In case of the introduction of a substituent(s) into the “optionally substituted aryl” or “optionally substituted heteroaryl”, the change of the functional group can be performed before or after reacting a carboxylic acid or its reactive derivative thereof (M-2) with the amine (M-1). For example, the compound having an aromatic heterocycle substituted with a nitro group can be prepared through the nitration of the compound with a nitrating acid. Moreover, the compound having an aromatic heterocycle substituted with an amino group can be prepared through the reduction of the above-obtained compound with tin in the presence of hydrochloride. Moreover, the compound having an aromatic heterocycle substituted with hydroxy group can be prepared through the diazonization of the above-obtained compound and the hydrolysis with alkali. On the other hand, the compound having an aromatic heterocycle substituted with an alkoxy group can be prepared through the reaction of the diazonium derivative with alcohol. The compound having an aromatic heterocycle substituted with halogen can be prepared through Sandmeyer reaction, the reaction of the diazonium derivative with a copper salt (e.g., CuCl₂, CuBr₂). The compound having an aromatic heterocycle substituted with halogen can be also prepared through the direct reaction of the compound having an aromatic heterocycle with chlorine and the like. Using the above-mentioned methods appropriately, halogen can be introduced into a desired position(s). The group of alkyl, alkenyl or acyl group can be directly introduced into an aromatic heterocycle through Friedel Crafts reaction with alkylating agent, an alkenylating agent, or an acylating agent, respectively, in the presence of anhydrous aluminum chloride.

[0116] The objective compound (I) of the present invention can be converted into a corresponding ester derivative, if desired. For example, the ester derivative can be prepared by esterification of a carboxylic acid in accordance with a known method.

[0117] When using the compound (I) of the present invention in treatment, it can be formulated into ordinary formulations for oral and parenteral administration. A pharmaceutical composition containing the compound (I) of the present invention can be in the form for oral and parenteral administration. Specifically, it can be formulated into formulations for oral administration such as tablets, capsules, granules, powders, syrup, and the like; or those for parenteral administration such as injectable solution or suspension for intravenous, intramuscular, or subcutaneous injection, inhalant, eye drops, nasal drops, suppositories, or percutaneous formulations such as ointment.

[0118] In preparing the formulations, carriers, excipients, solvents, and bases known to one having ordinary skill in the art may be used. In case of tablets, they are prepared by compressing or formulating an active ingredient together with auxiliary components. Examples of usable auxiliary components include pharmaceutically acceptable excipients such as binders (e.g., cornstarch), fillers (e.g., lactose, microcrystalline cellulose), disintegrants (e.g., starch sodium glycolate) or lubricants (e.g., magnesium stearate). Tablets may be coated appropriately. In case of liquid formulations such as syrups, solutions, or suspensions, they may contain suspending agents (e.g., methyl cellulose), emulsifiers (e.g., lecithin), preservatives, and the like. In case of injectable formulations, it may be in the form of solution, suspension, or oily or aqueous emulsion, which may contain suspension-stabilizing agents or dispersing agent, and the like. In case of an inhalant, it is formulated into a liquid formulation applicable to an inhaler. In case of eye drops, it is formulated into a solution or a suspension.

[0119] Especially, in case of a nasal drug for treating nasal blockage, it can be used as a solution or suspension prepared by a conventional formulating method, or administered as a powder formulated using a powdering agent (e.g., hydroxypropyl cellulose, carbopole) into the nasal cavity. Alternatively, it can be used as an aerosol filled into a special container together with a solvent of low boiling point.

[0120] Although an appropriate dosage of the compound (I) varies depending on the administration route, age, body weight, sex, or conditions of the patient, and the kind of drug(s) used together, if any, and should be determined by the physician in the end, in the case of oral administration, the daily dosage can generally be between 0.01–100 mg, preferably 0.01–10 mg, more preferably 0.01–1 mg, per kg body weight. In case of parenteral administration, the daily dosage can generally be between 0.001–100 mg, preferably 0.001–1 mg, more preferably 0.001–0. 1 mg, per kg body weight. The daily dosage can be administered in 1–4 divisions.

[0121] The following examples are provided to further illustrate the present invention and are not to be construed as limiting the scope.

[0122]
(Step 1)

[0123] To a solution of 251 mg (1.0 mmol) of (5Z)-7-[(1R,2S,3S,4S)-3-aminobicyclo[2.2.1]hept-2-yl]-5-heptenoic acid methyl ester (1) in 4 ml of tetrahydrofuran were added 257 mg (1.0 mmol) of 5 -(pyrrol-1-ylsulfonyl)thiophen-2-carboxylic acid and 13.5 mg (0.1 mmol) of 1-hydroxybenzotriazole. Under ice-cooling, 186 mg (1.2 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide was added thereto. The mixture was warmed to room temperature and stirred at 25° C. for 16 h. The mixture was diluted with water and extracted with toluene. The organic layer was washed with dilute hydrochloric acid and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was chromatographed on silica gel (toluene/ethyl acetate=6:1) to give 412 mg of (5Z)-7-{(1R,2S,3S,4S)-3-[5-(pyrrol-1-ylsulfonyl)-thiophen-2-ylcarbonylamino]-bicyclo[2.2.1]hept-2-yl}-5-heptenoic acid methyl ester (I-la). Yield 83.9%.

[0124] Colorless oil.

[0125] 300MHz ¹H-NMR(CDCl₃) δ: 1.08 (1H, m), 1.16–1.32 (2H, m), 1.56–1.73 (4H, m), 1.98–2.13 (5H, m), 2.31 (2H, t, J=7.2Hz), 2.56 (1H, m), 3.63 (3H, s), 3.79 (1H, m), 5.30–5.45 (2H, m), 6.28 (1H, d, J=7.5Hz), 6.33 and 7.16 (each 2H, each t, each J=2.1Hz), 7.40 and 7.57 (each 1H, each d, each J=3.9Hz).

(Step 2)

[0126] To a solution of 350 mg (0.713 mmol) of (5Z)-7-{(1R,2S,3S,4S)-3-[5-(pyrrol-1-ylsulfonyl)thiophen-2-ylcarbonylamino]-bicyclo[2.2.1]hept-2-yl}-5-heptenoic acid methyl ester (I-1a) in 1 ml of methanol and 0.5 ml of tetrahydrofuran was added under ice-cooling 0.5 ml (2.0 mmol) of 4N sodium hydroxide. The mixture was warmed to room temperature and stirred at 25° C. for 2 h. The reaction mixture was diluted with water and washed with ether. The aqueous layer was acidified with 0.5 ml of 5N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/hexane (3:4) to give 234 mg of (5Z)-7-{(1R,2S,3S,4S)-3-[5-(pyrrol-1-ylsulfonyl)-thiophen-2-ylcarbonylamino]-bicyclo[2.2.1]hept-2-yl}-5-heptenoic acid (I-1b) as needles.

[0127] Yield 68.8%. Mp. 113–114 ° C.

[0128] 300MHz ¹H-NMR(CDCl₃) δ: 1.09(1H, m), 1.17–1.32(2H, m), 1.34–1.52(2H, m), 1.56–1.75(4H, m), 2.00–2.18(5H, m), 2.35(2H, t, J=7.2Hz), 2.52(1H, m), 3.80(1H, m), 5.31–5.43(2H, m), 6.22(1H, d, J=6.0Hz), 6.35 and 7.17(each 2H, each t, each J=2.1Hz), 7.37 and 7.56(each 1H, each d, each J=3.9Hz).

[0129] IR(Nujol): 3369, 3143, 3124, 3068, 2678, 1710, 1626, 1593, 1374, 1200, 1171 cm⁻¹.

[0130] [α]_D^26.5+75.5±1.2° (c=1.004, MeOH)

[0131] Elemental Analysis (C₂₃H₂₈N₂O₆S₂) Calcd. (%): C, 57.96; H, 5.92; N, 5.88; S, 13.45 Found (%): C, 57.99; H, 5.88; N, 5.66; S, 13.50

[0132]
(Step 1)

[0133] Methyl (5Z)-7-[(1S,2R,3R,4R)-3-aminobicyclo[2.2.1]hept-2-yl]-5-heptenoate trifluoroacetate (2) (232 mg, 0.636 mmol), which was prepared by the method described in Reference Example 4 of the Japanese Patent Publication (Kokoku) No. 79060/1993, was dissolved in methylene chloride (5 ml). To the solution were added triethylamine (0.279 ml, 2.00 mmol) and 4-biphenylcarbonyl chloride under ice-cooling and stirred for 7 h at the same temperature. The reaction mixture was purified by column chromatography on silica gel (ethyl acetate/hexane (1:4)) to yield methyl (5Z)-7-[(1S,2R, 3R,4R)-3-(4-biphenyl)carbonylaminobicyclo[2.2.1]hept-2-yl]-5-heptenoate(I-2b) (221 mg, 0.512 mmol).

(Step 2)

[0134] The compound (I-2a) (190 mg, 0.440 mmol) was dissolved in methanol (6 ml). To the solution was added 1 N KOH (1.10 ml, 1.10 mmol) under ice-cooling and stirred for 15 h at room temperature. The reaction mixture was concentrated in vacuo. The residue, after the addition of water (20 ml) and 1 N HCl (2 ml), was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate/hexane (1:1) containing 0.3% acetic acid) to yield (5Z)-7-[(1S,2R,3R,4R)-3-(4-biphenyl)carbonylaminobicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (I-2b) (172 mg, 0.412 mmol). Yield 94%.

[0135]
(Step 1)

[0136] A mixture of 4.06 g (37 mmol) of thiophenol (3), 7.07 g (35 mmol) of 4-bromobenzoic acid (4), and 2,67 g (18.7 mmol) of copper oxide in 18 ml of quinoline was stirred under nitrogen gas at 190° C. for 1 h. The reaction mixture, cooled at 110° C. was added to 52 ml of 6N hydrochloric acid. The resulting precipitate was washed with 6N hydrochloric acid and water and recrystallized from ethyl acetate/hexane to yield 4.28 g of the compound (5).

[0137] Mp. 178–179° C. Yield 53%.

[0138] ¹H-NMR(CDCl₃) δ:7.21(2H,d,J=8.7Hz),7.40–7.42(3H,m), 7.50–7.53(2H,m),7.95(2H,d,J=8.7Hz).

[0139] IR(Nujol): 3523, 3062, 3007, 2884, 2670, 2549, 1730, 1690, 1595, 1561, 1491cm⁻¹

[0140] This preparation was carried out according to D. Hands, H. Marley, S. J. Skittrall and S. H B. Wright, J. Heterocyclic Chem., 23, 1333 (1986).

(Step2)

[0141] To a solution of 1.83 g (6.56 mmol) of methyl (5Z)-7-[(1R,2R,3S,5S)-2-amino-10-norpinan-3-yl]-5-heptenoate (6) in 3 ml of tetrahydrofuran were added 1.51 g (6.56 mmol) of 4-phenylthiobenzoic acid (5), 88 mg of 1-hydroxy benzotriazole and 1.32 g (8.53 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The mixture was allowed to stand at room temperature over night. The reaction mixture was diluted by diluted hydrochloric acid and extracted with toluene. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by column chromatography on silica gel (ethyl acetate/hexane (1:1)) to yield 3.181 g of the compound (II-1a) as oil. Yield: 98.4%.

[0142] [α]_D²²+61.8° (c=1.00, CH₃OH)

[0143] Elemental Analysis (C₃₀H₃₇NO₃S) Calcd.(%):C,73.28;H,7.59;N,2.85;S,6.52 Found(%):C,73.02;H,7.63;N,2.91;S,6.53

[0144] ¹H-NMR(CDCl₃) δ:0.96(1H,d,J=10.5Hz), 1.10 and 1.22 (each 3H, eachs), 1.49–1.73(3H,m),1.83–2.45(11H,m),3.62(3H,s),4.27(1H,m),5.32–5.49(2H,m),6.19(1H,d,J=8.1Hz),7.26(2H,d,J=8.4Hz),7.34–7.46(5H,m),7.62(2H,d,J=8.4Hz)

[0145] IR(CHCl₃): 3453, 3030, 3015, 2924, 2870, 1730, 1652, 1595, 1583, 1557, 1513, 1480 cm⁻¹

[0146] (Step 3)

[0147] To a solution of 3.181 g (6.47 mmol) of the compound (II-1a) in 32 ml of methanol was added 5.7 ml (22.6 mmol) of 4N sodium hydroxide. The mixture was stirred at 45° C. for 4.5 h. The mixture was neutralized with 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to yield 3.113 g of the compound (II-1b) as a colorless amorphous. Yield 99.5%.

[0148] [α]_D²²+61.0° (c=1.01,CH₃OH)

[0149] Elemental Analysis (C₂₉H₃₅NO₃S•0.1H₂O) Calcd.(%):C,72.65;H,7.48;N,2.92;S,6.69 Found(%):C,72.50;H,7.45;N,3.19;S,6.69

[0150] ¹H-NMR(CDCl₃) δ:0.96(1H,d,J=10.2Hz), 1.10 and 1.22 (each 3H, each s),1.51–1.79(3H,m),1.83–2.44(11H,m),4.26(1H,m),5.33–5.49(2H,m),6.21(1H,d,J=8.7Hz),7.25(2H,d,J=9.0Hz),7.34–7.47(5H,m),7.60(2H,d,J=9.0Hz)

[0151] IR(CHCl₃):3453, 3062, 3029, 3014, 2925, 2870, 1739, 1708, 1651, 1595, 1583, 1557,1515, 1481cm⁻¹

(Step 4)

[0152] To a solution of 3.113 g (6.5 mmol) of the above obtained compound (II-1b) in 30 ml of methanol was added 6.2 ml of 1 N sodium hydroxide. The mixture was concentrated under reduced pressure. The residue was dissolved in a small amount of ethyl acetate and mixed with hexane. The insoluble product was dissolved in 60 ml of water and freeze-dried to yield 3.138 g of the compound (I-1c) as a colorless amorphous. Yield 96.4%.

[0153] [α]_D²³+47.0° (c=1.00,CH₃OH)

[0154] Elemental Analysis (C₂₉H₃₄NO₃SNa•H₂O) Calcd.(%):C,67.29;H,7.01;N;2.71;S,6.19,Na,4.44 Found(%):C,67.17;H,7.00;N,2.75;S,6.29;Na,4.35

[0155] ¹H-NMR(CD₃OD) δ:0.964(1H,d,J=9.9Hz),1.13 and 1.22 (each 3H, eachs), 1.54–1.69(3H,m),1.94–2.39(11H,m),4.12(1H,bs),5.38–5.49(2H,m),7.25(1H,d,J=8.4Hz),7.36–7.46(5H,m),7.68(2H,d,J=8.4Hz)

[0156] IR (KBr): 3435, 3058, 2985, 2921, 2867, 1635, 1595, 1562, 1522, 1482, 1439, 1412cm⁻¹

[0157] The structure and physical property of the compound prepared in accordance with the above examples are shown below.

[0158]

TABLE 1
	Comp. No.	R
	I-3
	I-4
	I-5
	I-6
	I-7
	I-8
	I-9
	I-10
	I-11
	I-12
	I-13
	I-14
	I-15
	I-16
	I-17
	I-18
	I-19
	I-20
	I-21
	I-22

[0159]

TABLE 2
	Comp. No.	R
	I-23
	I-24
	I-25
	I-26
	I-27
	I-28
	I-29
	I-30
	I-31
	I-32
	I-33
	I-34
	I-35
	I-36
	I-37
	I-38
	I-39
	I-40
	I-41
	I-42

[0160]

TABLE 3
	Comp. No.	R
	I-43
	I-44
	I-45
	I-46
	I-47
	I-48
	I-49
	I-50
	I-51
	I-52
	I-53
	I-54
	I-55
	I-56
	I-57
	I-58
	I-59
	I-60
	I-61
	I-62

[0161]

TABLE 4
	Comp. No.	R
	I-63
	I-64
	I-65
	I-66
	I-67
	I-68
	I-69
	I-70
	I-71
	I-72
	I-73
	I-74
	I-75
	I-76
	I-77
	I-78
	I-79
	I-80
	I-81
	I-82

[0162]

TABLE 5
	Comp. No.	R
	I-83
	I-84
	I-85
	I-86
	I-87
	I-88
	I-89
	I-90
	I-91
	I-92
	I-93
	I-94
	I-95
	I-96
	I-97
	I-98
	I-99
	I-100
	I-101
	I-102

[0163]

TABLE 6
	Comp. No.	R
	I-103
	I-104
	I-105
	I-106
	I-107
	I-108
	I-109
	I-110
	I-111
	I-112
	I-113
	I-114
	I-115
	I-116
	I-117
	I-118
	I-119
	I-120
	I-121
	I-122

[0164]

TABLE 7
	Comp. No.	R
	I-123
	I-124
	I-125
	I-126
	I-127
	I-128
	I-129
	I-130
	I-131
	I-132
	I-133
	I-134
	I-135
	I-136
	I-137
	I-138
	I-139
	I-140
	I-141
	I-142

[0165]

TABLE 8
Comp. No.	R
I-143
I-144
I-145
I-146
I-147
I-148
I-149
I-150
I-151
I-152
I-153
I-154
I-155
I-156
I-157
I-158
I-159
I-160
I-161
I-162

[0166]

TABLE 9
	Comp. No.	R
	I-163
	I-164
	I-165
	I-166
	I-167
	I-168
	I-169
	I-170
	I-171
	I-172
	I-173
	I-174
	I-175
	I-176
	I-177
	I-178
	I-179
	I-180
	I-181
	I-182

[0167]

TABLE 10
Comp. No.	R
I-183
I-184
I-185
I-186
I-187
I-188
I-189
I-190
I-191
I-192
I-193
I-194
I-195
I-196
I-197
I-198
I-199
I-200
I-201
I-202

[0168]

TABLE 11
Comp. No.	R
I-203
I-204
I-205
I-206
I-207
I-208
I-209
I-210
I-211
I-212
I-213
I-214
I-215
I-216
I-217
I-218
I-219
I-220
I-221
I-222

[0169]

TABLE 12
Comp. No.	R
I-223
I-224
I-225
I-226
I-227
I-228
I-229
I-230
I-231
I-232
I-233
I-234
I-235
I-236
I-237
I-238
I-239
I-240
I-241
I-242

[0170]

TABLE 13
Comp. No.	R
I-243
I-244
I-245
I-246
I-247
I-248
I-249
I-250
I-251
I-252
I-253
I-254
I-255
I-256
I-257
I-258
I-259
I-260
I-261
I-262

[0171]

TABLE 14
Comp. No.	R
I-263
I-264
I-265
I-266
I-267
I-268
I-269
I-270
I-271
I-272
I-273
I-274
I-275
I-276
I-277
I-278
I-279
I-280
I-281
I-282

[0172]

TABLE 15
	Comp. No.	R
	I-283
	I-284
	I-285
	I-286
	I-287
	I-288
	I-289
	I-290
	I-291
	I-292
	I-293
	I-294

[0173]

TABLE 16
	Comp. No.	R
	II-2
	II-3
	II-4
	II-5
	II-6
	II-7
	II-8
	II-9
	II-10
	II-11
	II-12
	II-13
	II-14
	II-15
	II-16
	II-17
	II-18
	II-19
	II-20
	II-21

[0174]

TABLE 17
	Comp. No.	R
	II-22
	II-23
	II-24
	II-25
	II-26
	II-27
	II-28
	II-29
	II-30
	II-31
	II-32
	II-33
	II-34
	II-35
	II-36
	II-37
	II-38
	II-39
	II-40
	II-41

[0175]

TABLE 18
	Comp. No.	R
	II-42
	II-43
	II-44
	II-45
	II-46
	II-47
	II-48
	II-49
	II-50
	II-51
	II-52
	II-53
	II-54
	II-55
	II-56
	II-57
	II-58
	II-59
	II-60

[0176]

TABLE 19
	Comp. No.	R
	II-61
	II-62
	II-63
	II-64
	II-65
	II-66
	II-67
	II-68
	II-69
	II-70
	II-71
	II-72
	II-73
	II-74
	II-75
	II-76
	II-77
	II-78
	II-79
	II-80

[0177]

TABLE 20
Comp. No.	R
II-81
II-82
II-83
II-84
II-85
II-86
II-87
II-88
II-89
II-90
II-91
II-92
II-93
II-94
II-95
II-96
II-97
II-98
II-99
II-100

[0178]

TABLE 21
	Comp. No.	R
	II-101
	II-102
	II-103
	II-104
	II-105
	II-106
	II-107
	II-108
	II-109
	II-110
	II-111
	II-112
	II-113
	II-114
	II-115
	II-116
	II-117
	II-118
	II-119
	II-120

[0179]

TABLE 22
Comp. No.	R
II-121
II-122
II-123
II-124
II-125
II-126
II-127
II-128
II-129
II-130
II-131
II-132
II-133
II-134
II-135
II-136
II-137
II-138
II-139
II-140

[0180]

TABLE 23
Comp. No.	R
II-141
II-142
II-143
II-144
II-145
II-146
II-147
II-148
II-149
II-150
II-151
II-152
II-153
II-154
II-155
II-156
II-157
II-158
II-159
II-160

[0181]

TABLE 24
Comp. No.	R
II-161
II-162
II-163
II-164
II-165
II-166
II-167
II-168
II-169
II-170
II-171
II-172
II-173
II-174
II-175
II-176
II-177
II-178
II-179
II-180

[0182]

TABLE 25
Comp. No.	R
II-181
II-182
II-183
II-184
II-185
II-186
II-187
II-188
II-189
II-190
II-191
II-192
II-193
II-194
II-195
II-196
II-197
II-198
II-199
II-200

[0183]

TABLE 26
	Comp. No.	R
	II-201
	II-202
	II-203
	II-204

[0184]

TABLE 27
	Comp. No.	R
	III-1
	III-2
	III-3
	III-4

[0185]

TABLE 28
	Comp. No.	R
	IV-1
	IV-2

[0186]

TABLE 29
	Comp. No.	R
	V-1
	V-2
	V-3
	V-4
	V-5
	V-6
	V-7
	V-8
	V-9
	V-10
	V-11
	V-12

[0187]

TABLE 30
	Comp. No.	R
	VI-1

[0188] 300 MHz ¹H-NMR (CDCl₃-CD₃OD) δ: 1.23(1H, m), 1.28–1.32(2H, m), 1.44–1.53(2H, m), 1.57–1.74(4H, m), 2.03–2.14(5H, m), 2.32(2H, t, J=7.2Hz), 2.56(1H, m), 3.82(1H, m), 5.33–5.47(2H, m), 6.80(1H, m), 7.09–7.12(2H, m), 7.22(1H, t, J=8.1Hz), 7.63 and 7.86(each 1H, each d, each J=8.1Hz).

[0189] IR(CHCl₃): 3593 3442, 3111, 1710, 1644, 1519, 1449 cm⁻¹.

[0190] [α]_D²⁵+77.6±1.2° (c=1.010, MeOH)

[0191] Elemental Analysis (C₂₅H₂₉NO₄S•0.2H₂O) Calcd.(%): C, 67.76; H, 6.69; N, 3.16; S, 7.23 Found(%): C, 67.64; H, 6.77; N, 3.17; S, 7.18

[0192] 300MHz ¹H-NMR(CDCl₃) δ: 1.06(1H, m), 1.17–1.32(2H, m), 1.40–1.50(2H, m), 1.56–1.80(4H, m), 2.00–2.22(5H, m), 2.33(2H, t, J=7.2Hz), 2.53(1H, m), 3.84(3H, s), 3.85(1H, m), 5.29–5.42(2H, m), 6.18(1H, d, J=6.9Hz), 6.93, 7.10, 7.44 and 7.59(each 2H, each d-like).

[0193] IR(CHCl₃): 3516, 3448, 1708, 1650, 1594, 1514, 1494, 1483, 1288, 1248, 1032 cm⁻¹.

[0194] [α]_D²⁶+82.8±1.2° (c=1.000, MeOH)

[0195] Elemental Analysis (C₂₈H₃₃NO₄S•0.2H₂O) Calcd.(%): C, 69.59; H, 6.97; N, 2.90; S, 6.64 Found(%): C, 69.69; H, 6.93; N, 3.20; S, 6.57

[0196] 300MHz ¹H-NMR(CDCl₃) δ: 1.06(1H, m), 1.16–1.32(2H, m), 1.36–1.50(2H, m), 1.54–1.80(4H, m), 2.00–2.22(5H, m), 2.34(2H, t, J=7.2Hz), 2.53(1H, m), 3.82(1H, m), 3.83(3H, s), 5.29–5.42(2H, m), 6.14(1H, d, J=7.2Hz), 6.92(2H, d-like), 7.20–7.30(2H, m), 7.41–7.51(4H, m).

[0197] IR(CHCl₃): 3509, 3444, 2666, 1708, 1654, 1592, 1570, 1510, 1494, 1468, 1288, 1247, 1082 cm⁻¹.

[0198] [α]_D²⁶+58.4±1.4° (c=0.704, MeOH)

[0199] Elemental Analysis (C₂₈H₃₃NO₄S•0.2H₂O) Calcd.(%): C, 69.59; H, 6.97; N, 2.90; S, 6.64 Found(%): C, 69.55; H, 6.93; N, 3.03; S, 6.57

[0200] 300MHz ¹H-NMR(CDCl₃) δ: 1.11(1H, m), 1.20–1.34(2H, m), 1.42–1.52(2H, m), 1.56–1.78(4H, m), 2.00–2.23(5H, m), 2.35(2H, t, J=7.2Hz), 2.57(1H, m), 3.89(1H, m), 5.31–5.45(2H, m), 6.30(1H, d, J=7.2Hz), 6.37 and 7.12(each 2H, each 2H, each J=2.1Hz), 7.42 and 7.83(each 2H, each d-like).

[0201] IR(CHCl₃): 3518, 3448, 2662, 1708, 1653, 1609, 1499, 1334 cm⁻¹.

[0202] [α]_D²³+94.9±1.3° (c=1.005, MeOH)

[0203] Elemental Analysis (C₂₅H₃₀N₂O₃•0.1H₂O) Calcd.(%): C, 73.54; H, 7.45; N, 6.86 Found(%): C, 73.43; H, 7.46; N, 7.01

[0204] 300MHz ¹H-NMR(CDCl₃) δ: 1.12–1.76(9H, m), 1.96–2.24(5H, m), 2.33(2H, t, J=7.2Hz), 2.53(1H, m), 3.86(1H, m), 5.30–5.47(2H, m), 6.60(1H, d, J=6.9Hz), 7.05–7.23(5H, m), 7.55(1H, brs), 7.67 and 7.74(each 2H, each d, each J=8.7Hz).

[0205] IR(CHCl₃): 3516, 3439, 3368, 1708, 1653, 1600, 1519, 1496, 1487, 1401, 1347, 1165 cm⁻¹.

[0206] [α]D²⁵+69.9±1.1° (c=1.019, MeOH)

[0207] Elemental Analysis (C₂₇H₃₄N₂O₅S•0.1H₂O) Calcd.(%): C, 64.80; H, 6.89; N, 5.60; S, 6.41 Found(%): C, 64.73; H, 6.56; N, 5.74; S, 6.41

[0208] 300MHz ³H-NMR(CDCl₃) δ: 1.19–1.27(3H, m), 1.35–1.43(2H, m), 1.55–1.80(4H, m), 1.90–2.08(3H, m), 2.11–2.21(2H, m), 2.34(2H, t, J=7.2Hz), 2.53(1H, m), 3.74(1H, m), 5.29–5.48(2H, m), 6.44(1H, d, J=6.9Hz), 7.15(1H, d, J=1.5Hz), 7.46(2H, t, J=7.8Hz), 7.57(1H, m), 7.60(1H, d, J=1.5Hz), 7.76–7.78(2H, m), 7.89(1H, s).

[0209] IR(CHCl₃): 3440, 3360, 3107, 1708, 1637, 1518, 1448, 1329, 1163 cm⁻¹.

[0210] [α]_D²⁰+55.5±1.0° (c=1.003, MeOH)

[0211] Elemental Analysis (C₂₅H₃₀N₂O₅S₂•0.2H₂O) Calcd.(%): C, 59.31; H, 6.05; N, 5.53; S, 12.67 Found(%): C, 59.19; H, 6.12; N, 5.66; S, 12.50

[0212] mp.193–194° C.

[0213] 300MHz ¹H-NMR(d₆-DMSO) δ: 1.18–1.59(9H, m), 1.93(1H, d, J=2.4Hz), 1.99–2.07(4H, m), 2.21(2H, t, J=7.2Hz), 2.36(1H, m), 5.30–5.40(2H; m), 7.25(1H, d, J=1.5Hz), 7.54–7.63(3H, m), 7.69(1H, d, J=1.5Hz), 7.99–8.02(3H, m), 11.6(1H, s), 12.00(1H, brs).

[0214] IR(Nujol): 3367, 3221, 3186, 3091, 3055, 2654, 1711, 1631, 1566, 1541, 1321 cm⁻¹.

[0215] [α]_D²+74.6±1.1° (c=1.006, MeOH)

[0216] Elemental Analysis (C₂₆H₃₀N₂O₄S) Calcd.(%): C, 66.93; H, 6.48; N, 6.00; S, 6.87 Found(%): C, 66.76; H, 6.44; N, 5.88; S, 6.76

[0217] 300MHz ¹H-NMR(CDCl₃) δ: 1.08(1H, m), 1.18–1.34(2H, m), 1.40–1.50(2H, m), 1.56–1.77(4H, m), 2.00–2.20(5H, m), 2.35(2H, t, J=7.2Hz), 2.55(1H, m), 3.86(1H, m), 5.31–5.54(2H, m), 6.26(1H, d, J=7.8Hz), 6.31 and 7.14(each 2H, each t, each J=2.1Hz), 7.84 and 7.88(each 2H, each d, each J=8.4Hz).

[0218] IR(CHCl₃): 3515, 3441, 3144, 2669, 1708, 1662, 1515, 1486, 1455, 1376 cm⁻¹.

[0219] [α]_D²²+77.4±1.2° (c=1.004, MeOH)

[0220] Elemental Analysis (C₂₅H₃₀N₂O₅S•0.2H₂O) Calcd.(%): C, 63.32; H, 6.46; N, 6.91; S, 6.76 Found(%): C, 63.23; H, 6.49; N, 5.88; S, 6.67

[0221] 300MHz ¹H-NMR(CDCl₃) δ: 1.06(1H, m), 1.18–1.29(2H, m), 1.42–1.46(2H, m), 1.56–1.79(4H, m), 2.03–2.20(5H, m), 2.34(2H, t, J=7.2Hz), 2.52(1H, m), 3.82(1H, m), 4.12(2H, s), 5.29–5.43(2H, m), 6.04(1H, d, J=7.5Hz), 7.09(1H, d, J=1.5Hz), 7.22–7.34(5H, m), 7.67(1H, d, J=1.5Hz).

[0222] IR(CHCl₃): 3517, 3446, 2669, 1708, 1647, 1549, 1508, 1454 cm⁻¹.

[0223] [α]_D^21.5+68.8±1.1° (c=1.016, MeOH)

[0224] Elemental Analysis (C₂₆H₃₁NO₃S•0.1H₂O) Calcd.(%): C, 71.07; H, 7.16; N, 3.19; S, 7.30 Found(%): C, 71.05; H, 7.11; N, 3.38; S, 7.33

[0225] 300MHz ¹H-NMR(CDCl₃) δ: 1.09(1H, m), 1.10–1.30(2H, m), 1.40–1.46(2H, m), 1.56–1.77(4H, m), 2.00–2.22(5H, m), 2.33(2H, t, J=7.2Hz), 2.52(1H, m), 3.83(1H, m), 5.28–5.42(2H, m), 6.26(1H, d, J=6.9Hz), 7.15 and 7.63(each 2H, each d, each J=8.7Hz), 7.53(1H, m), 7.78–7.82(2H, m).

[0226] IR(CHCl₃): 3515, 3446, 3371, 3138, 1708, 1648, 1610, 1496, 1163 cm⁻¹.

[0227] [α]_D^22.5+66.5±1.1° (c=1.004, MeOH)

[0228] Elemental Analysis (C₂₇H₃₄N₂O₅S•0.4H₂O) Calcd.(%): C, 64.11; H, 6.93; N, 5.54; S, 6.34 Found(%): C, 64.05; H, 6.63; N, 5.56; S, 6.12

[0229] 300MHz ¹H-NMR(CDCl₃) δ: 1.19–1.31(3H, m), 1.36–1.44(2H, m), 1.55–1.78(4H, m), 1.85–2.02(2H, m), 2.05(1H, m), 2.13–2.47(4H, m), 2.57(1H, m), 3.71(1H, m), 5.31–5.54(2H, m), 6.53(1H, d, J=6.9Hz), 7.14–7.32(5H, m), 7.47(1H, br), 8.05 and 8.13(each 1H, each d, each J=1.5Hz).

[0230] IR(CHCl₃): 3509, 3360, 3262, 1709, 1649, 1542, 1496, 1349, 1160 cm⁻¹.

[0231] [α]_D²³+59.1±1.1° (c=1.001, MeOH)

[0232] Elemental Analysis (C₂₅H₃₀N₂O₅S₂•0.2H₂O) Calcd.(%): C, 59.31; H, 6.05; N, 5.53; S, 12.67 Found(%): C, 59.17; H, 6.01; N, 5.49; S, 12.37

[0233] 300MHz ¹H-NMR(CDCl₃) δ: 1.18–1.32(3H, m), 1.38–1.47(2H, m), 1.55–1.78(4H, m), 1.90–2.08(3H, m), 2.15–2.31(2H, m), 2.32–2.49(2H, m), 2.59(1H, m), 3.74(1H, m), 5.33–5.53(2H, m), 6.35 and 7.17(each 2H, each t, each J=2.4Hz), 6.47(1H, d, J=6.3Hz), 8.21 and 8.22(each 1H, each d, each J=1.5Hz).

[0234] IR(CHCl₃): 3506, 3412, 3144, 3107, 1727, 1709, 1656, 1540, 1504, 1456, 1382, 1166 cm⁻¹.

[0235] [α]_D²³+63.8±1.0° (c=1.005, MeOH)

[0236] Elemental Analysis (C₂₃H₂₈N₂O₅S₂•0.2H₂O) Calcd.(%): C, 57.53; H, 5.96; N, 5.83; S, 13.35 Found(%): C, 57.44; H, 5.96; N, 6.00; S, 13.35

[0237] mp.128–130° C.

[0238] 300MHz ¹H-NMR(CDCl₃) δ: 1.16–1.34(3H, m), 1.40–1.81(6H, m), 2.37(2H, t, J=7.2Hz), 2.57(1H, m), 3.89(1H, m), 5.35–5.51(2H, m), 6.37 and 7.20(each 2H, each d, each J=2.4Hz), 7.23(1H, d, J=8.7Hz).

[0239] IR(Nujol): 3371, 3097, 2662, 1716, 1703, 1671, 1652, 1530, 1367, 1361, 1187, 1162 cm⁻¹.

[0240] [α]_D²⁵+47.5±0.9° (c=1.003, MeOH)

[0241] Elemental Analysis (C₂₃H₂₈N₂O₅S₂) Calcd.(%): C, 57.96; H, 5.92; N, 5.88; S, 13.45 Found(%): C, 58.05; H, 5.91; N, 5.83; S, 13.38

[0242] 300MHz ¹H-NMR(CDCl₃) δ: 1.09(1H, m), 1.20–1.32(2H, m), 1.42–1.47(2H, m), 1.58–1.75(4H, m), 2.01(3H, d, J=1.2Hz), 2.00–2.16(5H, m), 2.35(2H, t, J=7.2Hz), 2.55(1H, m), 3.86(1H, m), 5.31–5.44(2H, m), 6.14(1H, dd, J=1.5 and 3.0Hz), 6.29(1H, d, J=7.5Hz), 6.86(1H, m), 7.04(1H, t, J=3.0Hz), 7.84(4H, s).

[0243] IR(CHCl₃): 3517, 3441, 2667, 1708, 1661, 1515, 1485, 1375, 1260, 1178 cm⁻¹.

[0244] [α]_D²⁵+73.8±1.1° (c=1.001, MeOH)

[0245] Elemental Analysis (C₂₆H₃₂N₂O₅S•0.1H₂O) Calcd.(%): C, 64.20; H, 6.67; N, 5.76; S, 6.59 Found(%): C, 64.14; H, 6.65; N, 5.85; S, 6.86

[0246] 300MHz ¹H-NMR(CDCl₃) δ: 1.20–1.31(3H, m), 1.40–1.47(2H, m), 1.57–1.80(4H, m), 2.00–2.30(5H, m), 2.37(2H, t, J=6.9Hz), 2.60(1H, m), 3.84(1H, m), 5.32–5.50(2H, m), 6.32(2H, t, J=2.4Hz), 6.63(1H, d, J=6.6Hz), 7.16(2H, t, J=2.4Hz), 7.55(1H, t, J=8.0Hz), 7.89(1H, m), 8.06(1H, d, J=7.8Hz), 8.30(1H, t, J=1.7Hz).

[0247] IR(CHCl₃): 3394, 3145, 1726, 1709, 1659, 1374 cm⁻¹.

[0248] [α]_D²⁵+6.03±1.0° (c=1.000, MeOH)

[0249] Elemental Analysis (C₂₅H₃₀N₂O₅S•0.2H₂O) Calcd.(%): C, 63.32; H, 6.46; N, 5.91; S, 6.76 Found(%): C, 63.39; H, 6.50; N, 6.16; S, 6.80

[0250] 300MHz ¹H-NMR(CDCl₃) δ: 1.10(1H, m), 1.20–1.32(2H, m), 1.45(2H, t, J=6.9Hz), 1.58–1.74(4H, m), 2.04–2.16(5H, m), 2.28(3H, s), 2.35(2H, t, J=6.9Hz), 2.55(1H, m), 3.87(1H, m), 5.31–5.44(2H, m), 5.96(1H, m), 6.18(1H, t, J=3.3Hz), 6.32(1H, d, J=7.5Hz), 7.25(1H, dd, J=1.8 and 3.3Hz), 7.78 and 7.85(each 2H, each d, each J=8.7Hz).

[0251] IR(CHCl₃): 3514, 3441, 1708, 1661, 1515, 1487, 1368, 1164 cm⁻¹.

[0252] [α]_D²⁵+74.0±1.1° (c=1.004, MeOH)

[0253] Elemental Analysis (C₂₆H₃₂N₂O₅S•0.2H₂O) Calcd.(%): C, 63.96; H, 6.69; N, 5.74; S, 6.57 Found(%): C, 63.97; H, 6.69; N, 5.98; S, 6.54

[0254] 300MHz ¹H-NMR(CDCl₃) δ: 1.07(1H, m), 1.18–1.31(2H, m), 1.41–1.49(2H, m), 1.56–1.76(4H, m), 2.00–2.21(5H, m), 2.34(2H, t, J=7.2Hz), 2.55(1H, m), 3.86(1H; m), 5.09(2H, s), 5.29–5.43(2H, m), 6.19(2H, t, J=2.1Hz), 6.25(1H, d, J=7.5Hz), 6.67(2H, t, J=2.1Hz), 7.13 and 7.70(each 2H, each d, each J=8.4Hz).

[0255] IR(CHCl₃): 3517, 3446, 3103, 2667, 1708, 1653, 1523, 1497 cm⁻¹.

[0256] [α]_D²⁵+57.7±1.0° (c=1.010, MeOH)

[0257] Elemental Analysis (C₂₆H₃₂N₂O₃) Calcd.(%): C, 73.63; H, 7.70; N, 6.60 Found(%): C, 73.72; H, 7.77; N, 6.76

[0258] 300MHz ¹H-NMR(CDCl₃) δ: 1.05(1H, m), 1.15–1.30(2H, m), 1.36–1.45(2H, m), 1.55–1.72(4H, m), 2.00–2.14(5H, m), 2.32(2H, t, J=7.2Hz), 2.51(1H, m), 3.82(1H, m), 5.28–5.42(2H, m), 6.22(2H, d, J=7.5Hz), 6.68(1H, d, J=3.6Hz), 7.22–7.34(2H, m), 7.52–7.55(2H, m), 7.76 and 7.88(each 2H, each d, each J=8.7Hz), 7.97(1H, d, J=8.1Hz).

[0259] IR(CHCl₃): 3510, 3480, 3440, 3145, 3117, 1708, 1661, 1516, 1485, 1445, 1377, 1130 cm⁻¹.

[0260] [α]D²⁵+65.9±1.1° (c=1.010, MeOH)

[0261] Elemental Analysis (C₂₉H₃₂N₂O₅S•S0.3H₂O) Calcd.(%): C, 66.21; H, 6.25; N, 5.33; S,6.10 Found(%): C, 66.34; H, 6.30; N, 5.63; S,5.84

[0262] 300MHz ¹H-NMR(CDCl₃) δ: 1.13(1H, m), 1.20–1.31(2H, m), 1.44(2H, t, J=6.8Hz), 1.59–1.72(4H, m), 2.03–2.20(5H, m), 2.32(2H, t, J=7.2Hz), 2.54(1H, m), 3.83(1H, m), 4.62(2H, s), 5.31–5.45(2H, m), 6.25–6.26(2H, m), 6.57(1H, d, J=7.2Hz), 7.25(1H, m), 7.81(4H, s).

[0263] IR(CHCl₃): 3581, 3518, 3440, 3149, 1708, 1660, 1517, 1486, 1371, 1150 cm⁻¹.

[0264] [α]_D²⁷+72.2±1.1° (c=1.007, MeOH)

[0265] Elemental Analysis (C₂₆H₃₂N₂O₆S) Calcd.(%): C, 62.38; H, 6.44; N, 5.60; S,6.40 Found(%): C, 62.17; H, 6.52; N, 5.71; S,6.40

[0266] 300MHz ¹H-NMR(d₆-DMSO) δ: 1.18–1.33(3H, m), 1.43–1.60(6H, m), 1.92–2.30(5H, m), 2.20(2H, t, J=7.5Hz), 2.38(1H, m), 3.67(1H, m), 5.30–5.36(2H, m), 6.85(1H, d, J=4.8Hz), 7.27(1H, d, J=4.8Hz), 7.86 and 7.94(each 2H, each d, each J=8.7Hz), 8.37(1H, d, J=6.9Hz).

[0267] IR(KBr): 3360, 3151, 3103, 1707, 1635, 1569, 1530, 1328, 1284, 1140 cm⁻¹.

[0268] [α]_D²⁷+67.4±1.1° (c=1.007, DMSO)

[0269] Elemental Analysis (C₂₄H₂₉N₃O₅S₂•0.3H₂O) Calcd.(%): C, 56.62; H, 5.86; N, 8.24; S,12.60 Found(%): C, 56.74; H, 5.96; N, 8.30; S,12.31

[0270] mp.231–232° C.

[0271] 300MHz ¹H-NMR(d₆-DMSO) δ: 1.19–1.61(9H, m), 1.95–2.08(5H, m), 2.21(2H, t, J=7.2Hz), 2.40(1H, m), 3.71(1H, m), 5.34–5.37(2H, m), 7.31 and 7.59(each 1H, each d, each J=3.6Hz), 7.98 and 8.16(each 2H, each d, each J=8.7Hz), 8.41(1H, d, J=7.2Hz).

[0272] IR(KBr): 3336, 3185, 2541, 1675, 1631, 1548, 1324, 1295, 1163 cm⁻¹.

[0273] [α]_D²⁷+84.5±1.3° (c=1.000, DMSO)

[0274] Elemental Analysis (C₂₄H29N₃O₄S) Calcd.(%): C, 64.22; H, 6.25; N, 8.99; S,6.86 Found(%): C, 64.13; H, 6.10; N, 8.92; S,7.08

[0275] 300MHz ¹H-NMR(CDCl₃) δ: 1.14(1H, m), 1.22–1.35(2H, m), 1.44–1.53(2H, m), 1.58–1.78(4H, m), 2.02–2.28(5H, m), 2.36(2H, t, J=7.2Hz), 2.58(1H, m), 3.87(1H, m), 5.15–5.48(2H, m), 6.29 and 7.18(each 2H, each t, J=2.4Hz), 6.38(1H, d, J=7.2Hz), 7.77(1H, dd, J=1.8 and 8.7Hz), 7.82(1H, s), 7.91(1H, d, J=8.7Hz), 8.34(1H, d, J=1.8Hz).

[0276] IR(CHCl₃): 3512, 3441, 3423, 3144, 2670, 1708, 1530, 1501, 1374, 1164 cm⁻¹.

[0277] [α]_D²⁶+96.1±1.4° (c=1.006, MeOH)

[0278] Elemental Analysis (C₂₇H₃₀N₂O₅S₂•0.2H₂O) Calcd.(%): C, 61.16; H, 5.78; N, 5.28; S, 12.09 Found(%): C, 61.17; H, 5.74; N, 5.35; S, 12.12

[0279] 300MHz ¹H-NMR(CDCl₃) δ: 1.06(1H, m), 1.17–1.31(2H, m), 1.39–1.48(2H, m), 1.56–1.77(4H, m), 1.99–2.20(5H, m), 2.34(2H, t, J=7.2Hz), 2.53(1H, m), 3.84(1H, m), 5.29–5.42(2H, m), 6.20(1H, d, J=7.2Hz), 7.10–7.17(3H, m), 7.32(1H, dd, J=1.2 and 3.6Hz), 7.54(1H, dd, J=1.2 and 5.4Hz), 7.60–7.64(2H, m).

[0280] IR(CHCl₃): 3518, 3447, 2669, 1708, 1651, 1596, 1515, 1483 cm⁻¹.

[0281] [α]_D²⁶+84.7±1.2° (c=1.003, MeOH)

[0282] Elemental Analysis (C₂₅H₂₉NO₃S₂•0.1H₂O) Calcd.(%): C, 65.64; H, 6.43; N, 3.06; S, 14.02 Found(%): C, 65.58; H, 6.41; N, 3.10; S, 13.82

[0283] 300MHz ¹H-NMR(CDCl₃) δ: 1.13(1H, m), 1.20–1.33(2H, m), 1.41–1.50(2H, m), 1.56–1.77(4H, m), 2.00–2.21(5H, m), 2.37(2H, t, J=7.2Hz), 2.55(1H, m), 3.87(1H, m), 5.31–5.45(2H, m), 6.48(1H, d, J=7.2Hz), 7.10(1H, dd, J=3.9 and 5.1Hz), 7.68(1H, dd, J=1.2 and 5.1Hz), 7.69(1H, dd, J=1.2 and 3.9Hz), 7.84–7.88 and 7.95–7.99(each 2H, each m).

[0284] IR(CHCl₃): 3518, 3441, 3382, 1708, 1659, 1515, 1329, 1158 cm⁻¹.

[0285] [α]_D²⁶+75.7±1.2° (c=1.000, MeOH)

[0286] Elemental Analysis (C₂₅H₂₉NO₅S₂) Calcd.(%): C, 61.58; H, 5.99; N, 2.87; S, 13.15 Found(%): C, 61.36; H, 6.05; N, 2.91; S, 13.13

[0287] mp.213–215° C.

[0288] 300MHz ¹H-NMR(d₆-DMSO) δ: 1.18–1.61(9H, m), 1.95–2.10(5H, m), 2.21(2H, t, J=7.5Hz), 2.40(1H, m), 3.71(1H, m), 5.33–5.38(2H, m), 7.19(1H, m), 7.87(1H, m), 7.96 and 8.10(each 2H, each d, each J=8.2Hz), 8.21(1H, d, J=8.6Hz), 8.40(1H, m), 10.92(1H, s), 12.05(1H, brs).

[0289] IR(Nujol): 3337, 3249, 3205, 3132, 2524, 1678, 1632, 1545, 1433, 1305 cm⁻¹.

[0290] [α]_D²³+85.2±2.5° (c=0.505, MeOH)

[0291] Elemental Analysis (C₂₇H₃₁N₃O₄•0.3H₂O) Calcd.(%): C, 69.72; H, 6.80; N, 9.03 Found(%): C, 69.76; H, 6.75; N, 8.76

[0292] 300MHz ¹H-NMR(CDCl₃) δ: 1.07(1H, m), 1.18–1.32(2H, m), 1.40–1.50(2H, m), 1.56–1.78(4H, m), 2.00–2.21(5H, m), 2.34(2H, t, J=7.2Hz), 2.54(1H, m), 3.85(1H, m), 5.29–5.42(2H, m), 6.17(1H, d, J=6.9Hz), 7.07(1H, dd, J=1.2 and 5.1Hz), 7.15(2H, d J=8.7Hz), 7.43(1H, dd, J=3.0 and 5.1Hz), 7.51(1H, dd, J=1.2 and 3.0Hz), 7.62(2H, d, J=8.7Hz).

[0293] IR(CHCl₃): 3510, 3447, 3110, 2666, 1708, 1651, 1596, 1515, 1482 cm⁻¹.

[0294] [α]_D²⁷+85.9±1.3° (c=1.007, MeOH)

[0295] Elemental Analysis (C₂₅H₂₉NO₃S₂) Calcd.(%): C, 65.90; H, 6.42; N, 3.07; S, 14.07 Found(%): C, 65.60; H, 6.36; N, 3.36; S, 13.86

[0296] mp. 123–125° C.

[0297] 300MHz ¹H-NMR(CDCl₃) δ: 1.12(1H, m), 1.18–1.34(2H, m), 1.42–1.50(2H, m), 1.56–1.78(4H, m), 2.02–2.21(5H, m), 2.35(2H, t, J=7.2Hz), 2.55(1H, m), 3.88(1H, m), 5.31–5.45(2H, m), 6.42(1H, d, J=6.0Hz), 7.31(1H, d, J=5.1Hz), 7.40(1H, dd, J=3.0 and 5.1Hz), 7.87 and 7.96(each 2H, each d, each J=8.7Hz), 8.11(1H, d, J=3.0Hz).

[0298] IR(Nujol): 3286, 3108, 2671, 1701, 1641, 1546, 1327, 1156 cm⁻¹.

[0299] [α]_D²⁷+75.3±1.2° (c=1.004, MeOH)

[0300] Elemental Analysis (C₂₅H₂₉NO₅S₂) Calcd.(%): C, 61.58; H, 5.99; N, 2.87; S, 13.15 Found(%): C, 61.39; H, 5.94; N, 3.02; S, 12.99

[0301] 300MHz ¹H-NMR(CDCl₃) δ: 1.12(1H, m), 1.23–1.34(2H, m), 1.43–1.52(2H, m), 1.58–1.79(4H, m), 2.02–2.24(5H, m), 2.36(2H, t, J=7.2Hz), 2.53(1H, m), 3.87(1H, m), 5.32–5.45(2H, m), 6.11(1H, d, J=3.6Hz), 6.28(1H, d, J=7.5Hz), 6.35 and 7.09(each 2H, each t, each J=2.1Hz), 7.16(1H, d, J=3.6Hz).

[0302] IR(CHCl₃): 3512, 3438, 3142, 1741, 1709, 1653, 1623, 1564, 1508 cm⁻¹.

[0303] [α]_D²⁵+102.4±1.4° (c=1.006, MeOH)

[0304] Elemental Analysis (C₂₃H₂₈N₂O₄•0.2H₂O) Calcd.(%): C, 69.05; H, 7.15; N, 7.00 Found(%): C, 69.12; H, 7.10; N, 6.95

[0305] 300MHz ¹H-NMR(CDCl₃) δ: 1.04(1H, m), 1.08–1.28(2H, m), 1.41–1.46(2H, m), 1.55–1.78(4H, m), 1.99–2.16(5H, m), 2.34(2H, t, J=7.2Hz), 2.51(1H, m), 3.81(1H, m), 4.13(2H, s), 5.29–5.42(2H, m), 5.96(1H, d, J=8.1Hz), 6.77(1H, ddd, J=0.9, 0.9 and 3.9Hz), 7.20–7.35(5H, m), 7.37(1H, d, J=3.9Hz).

[0306] IR(CHCl₃): 3511, 3445, 2670, 1708, 1642, 1544, 1507, 1455 cm⁻¹.

[0307] [α]_D²⁶+67.1±1.1° (c=1.015, MeOH)

[0308] Elemental Analysis (C₂₆H₃₁NO₃S) Calcd.(%): C, 71.36; H, 7.14; N, 3.20; S, 7.33 Found(%): C, 71.19; H, 7.16; N, 3.34; S, 7.26

[0309] 300MHz ¹H-NMR(CDCl₃) δ: 1.22–1.85(9H, m), 1.95–2.53(7H, m), 2.66(1H, m), 3.84(1H, m), 5.37–5.60(2H, m), 6.79(1H, d, J=6.0Hz), 7.01–7.17(5H, m), 7.83(1H, dd, J=1.5 and 8.7Hz), 7.53(1H, d, J=8.7Hz), 7.89(1H, s), 8.35(1H, s), 8.83(1H, d, J=1.5Hz).

[0310] IR(CHCl₃): 3509, 3437, 3364, 3209, 1710, 1634, 1495, 1344, 1158 cm⁻¹.

[0311] [α]_D²⁶+36.6±0.8° (c=1.005, MeOH)

[0312] Elemental Analysis (C₂₉H₃₂N₂O₅S₂•0.2H₂O) Calcd.(%): C, 62.61; H, 5.87; N, 5.04; S, 11.53 Found(%): C, 62.53; H, 5.87; N, 5.21; S, 11.42

[0313] 300MHz ¹H-NMR(CDCl₃) δ: 1.13(1H, m), 1.20–1.37(2H, m), 1.46–1.56(2H, m), 1.60–1.80(4H, m), 2.02–2.28(5H, m), 2.38(2H, t, J=7.2Hz), 2.64(1H, m), 3.94(1H, m), 5.35–5.50(2H, m), 6.21(1H, d, J=7.2Hz), 6.28 and 7.21(each 2H, each t, each J=2.4Hz), 7.81(1H, dd, J=1.8 and 8.7Hz), 7.91(1H, d, J=8.7Hz), 7.99(1H, s), 8.97(1H, d, J=1.8Hz).

[0314] IR(CHCl₃): 3513, 3438, 3144, 3096, 1708, 1656, 1518, 1374 cm⁻¹.

[0315] [α]_D²⁶+40.1±0.8° (c=1.010, MeOH)

[0316] Elemental Analysis (C₂₇H₃₀N₂O₅S₂•0.2H₂O) Calcd.(%): C, 61.16; H, 5.78; N, 5.28; S,12.09 Found(%): C, 61.16; H, 5.76; N, 5.43; S,12.05

[0317] 300MHz ¹H-NMR(CDCl₃) δ: 1.18–1.35(3H, m), 1.40–1.48(2H, m), 1.57–1.79(4H, m), 1.99–2.21(5H, m), 2.37(2H, t, J=7.2Hz), 2.50(1H, m), 3.80(1H, m), 5.32–5.47(2H, m), 6.38(2H, t, J=2.4Hz), 6.54(1H, d, J=7.5Hz), 7.12 and 7.13(each 1H, each d, each J=3.6Hz), 7.20(2H, t, J=2.4Hz).

[0318] IR(CHCl₃): 3512, 3433, 3144, 2686, 1708, 1669, 1591, 1528, 1475, 1457, 1394 cm⁻¹.

[0319] [α]_D²⁶+74.3±1.1° (c=1.007, MeOH)

[0320] Elemental Analysis (C₂₃H₂₈N₂O₅S) Calcd.(%): C, 59.98; H, 6.13; N, 6.08; S, 6.96 Found(%): C, 59.71; H, 6.22; N, 6.10; S, 7.02

[0321] mp.102–103° C.

[0322] 300MHz ¹H-NMR(CDCl₃) δ: 1.05(1H, m), 1.18–1.30(2H, m), 1.38–1.48(2H, m), 1.55–1.78(4H, m), 1.99–2.19(5H, m), 2.35(2H, t, J=7.2Hz), 2.52(1H, m), 3.81(1H, m), 5.20(2H, d, J=0.9Hz), 5.30–5.42(2H, m), 5.99(1H, d, J=7.2Hz), 6.20 and 6.71 (each 2H, each t, each J=2.1Hz), 6.86(1H, td, J=0.9 and 3.9Hz), 7.37(1H, d, J=3.9Hz).

[0323] IR(Nujol): 3393, 3093, 6064, 2669, 1704, 1616, 1523, 1522 cm⁻¹.

[0324] [α]_D²⁶+71.1±1.1° (c=1.005, MeOH)

[0325] Elemental Analysis (C₂₄H₃₀N₂O₃S) Calcd.(%): C, 67.58; H, 7.09; N, 6.57; S, 7.52 Found(%): C, 67.45; H, 7.09; N, 6.58; S, 7.67

[0326] 300MHz ¹H-NMR(CDCl₃) δ: 1.07(1H, m), 1.18–1.31(2H, m), 1.40–1.48(2H, m), 1.56–1.78(4H, m), 2.00–2.20(5H, m), 2.35(2H, t, J=7.2Hz), 2.53(1H, m), 3.82(1H, m), 5.31–5.43(2H, m), 6.02(1H, d, J=7.2Hz), 7.15 and 7.44 (each 1H, each d, each J=3.9Hz), 7.20–7.33(5H, m).

[0327] IR(CHCl₃): 3511, 3444, 3426, 3031, 2665, 1708, 1646, 1530, 1499, 1477, 1421, 1318 cm⁻¹.

[0328] [α]D²⁶+74.8±1.1° (c=1.004, MeOH)

[0329] Elemental Analysis (C₂₅H₂₉NO₃S₂) Calcd.(%): C, 65.90; H, 6.42; N, 3.07; S, 14.07 Found(%): C, 65.61; H, 6.40; N, 3.19; S, 14.18

[0330] 300MHz ¹H-NMR(CDCl₃) δ: 1.09(1H, m), 1.17–1.31(2H, m), 1.38–1.47(2H, m), 1.54–1.74(4H, m), 2.00–2.17(5H, m), 2.34(2H, t, J=7.2Hz), 2.52(1H, m), 3.80(1H, m), 5.30–5.43(2H, m), 6.27(1H, d, J=7.2Hz), 7.41(1H, d, J=4.2Hz), 7.51–7.64(4H, m), 7.98(2H, m).

[0331] IR(CHCl₃): 3515, 3442, 3366, 1708, 1656, 1530, 1504, 1327, 1156 cm⁻¹.

[0332] [α]_D²⁶+73.1±1.1° (c=1.004, MeOH)

[0333] Elemental Analysis (C₂₅H₂₉NO₅S₂•0.2H₂O) Calcd.(%): C, 61.13; H, 6.03; N, 2.85; S, 13.05 Found(%): C, 60.94; H, 6.02; N, 2.86; S, 13.12

[0334] mp. 163–165° C.

[0335] 300MHz ¹H-NMR(CDCl₃) δ: 1.24–1.43(3H, m), 1.52–1.87(8H, m), 2.10(1H, d, J=3.0Hz), 2.30–2.55(4H, m), 2.71(1H, m), 3.66(1H, m), 5.38 and 5.63(each 1H, each m), 7.13(1H, d, J=1.5Hz), 7.34(1H, d, J=5.4Hz), 7.49–7.60(3H, m), 7.86–7.89(2H, m), 8.49(1H, s), 8.69(1H, d, J=1.5Hz).

[0336] IR(KBr): 3367, 3261, 3090, 1726, 1645, 1618, 1589, 1577, 1535, 1513, 1426, 1396, 1289, 1197 cm⁻¹.

[0337] [α]_D²³+84.5∓1.2° (c=1.006, MeOH)

[0338] Elemental Analysis (C₂₆H₃₀N₂O₄S) Calcd.(%): C, 66.93; H, 6.48; N, 6.00; S, 6.87 Found(%): C, 66.97; H, 6.36; N, 6.01; S, 6.89

[0339] 300MHz ¹H-NMR(CDCl₃) δ: 1.25–1.80(9H, m), 1.87–2.05(3H, m), 2.14–2.29(2H, m), 2.37(2H, t, J=6.9Hz), 2.57(1H, m), 3.73(1H, m), 5.35 and 5.49(each 1H, each m), 6.71(1H, d, J=6.6Hz), 6.87(1H, d, J=1.5Hz), 7.43–7.48(2H, m), 7.56(1H, m), 7.63(1H s), 7.64((1H, j, J=1.5Hz), 7.73–7.76(2H, m).

[0340] IR(CHCl₃): 3510, 3379, 3247, 3108, 1709, 1637, 1556, 1516, 1448, 1365, 1319, 1161 cm⁻¹.

[0341] [α]_D²³+61.1±1.0° (c=1.004, MeOH)

[0342] Elemental Analysis (C₂₅H₃₀N₂O₅S₂•0.2H₂O) Calcd.(%): C, 59.31; H, 6.05; N, 5.53; S, 12.67 Found(%): C, 59.38; H, 6.11; N, 5.75; S, 12.41

[0343] 300MHz ¹H-NMR(CDCl₃) δ: 1.11(1H, m), 1.24–1.31(2H, m), 1.44–1.52(2H, m), 1.60–1.79(4H, m), 2.00–2.21(5H, m), 2.37(2H, t, J=7.2Hz), 2.56(1H, m), 3.86(1H, m), 5.32–5.46(2H, m), 6.11(1H, d, J=7.8Hz), 7.25 and 7.49(each 1H, each d, each J=4.2Hz), 7.30–7.43(3H, m), 7.60–7.63(2H, m).

[0344] IR(CHCl₃): 3510, 3445, 3428, 1739, 1708, 1643, 1540, 1510, 1491, 1454 cm⁻¹.

[0345] [α]_D³⁵+88.0±1.3° (c=1.012, MeOH)

[0346] Elemental Analysis (C₂₅H₂₉NO₃S•0.2H₂O) Calcd.(%): C, 70.29; H, 6.94; N, 3.28; S, 7.51 Found(%): C, 70.35; H, 7.01; N, 3.59; S, 7.46

[0347] 300MHz ¹H-NMR(CDCl₃) δ: 1.13(1H, m), 1.22–1.32(2H, m), 1.46–1.51(2H, m), 1.60–1.76(4H, m), 2.04–2.17(5H, m), 2.36(2H, t, J=7.2Hz), 2.57(1H, m), 3.86(1H, m), 5.32–5.46(2H, m), 6.30(1H, d, J=8.4Hz), 7.48–7.65(5H, m), 7.84–7.88(2H, m).

[0348] IR(CHCl₃): 3511, 3443, 3425, 1708, 1643, 1529, 1506, 1448 cm⁻¹.

[0349] [α]_D²⁵+92.4±1.3° (c=1.000, MeOH)

[0350] Elemental Analysis (C₂₆H₂₉NO₄S₂•0.2H₂O) Calcd.(%): C, 68.61; H, 6.51; N, 3.08; S, 7.04 Found(%): C, 68.55; H, 6.52; N, 3.13; S, 7.03

[0351] 300MHz ¹H-NMR(CDCl₃) δ: 1.10(1H, m), 1.27–1.31(2H, m), 1.49(2H, brs), 1.59–1.80(4H, m), 2.00–2.20(5H, m), 2.36(2H, t, J=7.2Hz), 2.55(1H, m), 3.85(1H, m), 5.31–5.45(2H, m), 6.14(1H, d, J=7.2Hz), 7.13(1H, d, J=3.9Hz), 7.30(1H, dd, J=1.2 and 5.1Hz), 7.36(1H, dd, J=3.0 and 5.1Hz), 7.45–7.46(2H, m).

[0352] IR(CHCl₃): 3511, 3445, 3428, 3109, 1708, 1642, 1523, 1499, 1456 cm⁻¹.

[0353] [α]_D²⁵+82.9±1.2° (c=1.006, MeOH)

[0354] Elemental Analysis (C₂₃H₂₇NO₃S₂•0.1H₂O) Calcd.(%): C, 64.04; H, 6.36; N, 3.25; S, 14.86 Found(%): C, 63.99; H, 6.52; N, 3.23; S, 14.85

[0355] 300MHz ¹H-NMR(CDCl₃) δ: 1.10(1H, m), 1.22–1.31(2H, m), 1.46–1.51(2H, m), 1.60–1.80(4H, m), 2.03–2.22(5H, m), 2.37(2H, t, J=7.2Hz), 2.55(1H, m), 3.85(1H, m), 5.32–5.45(2H, m), 6.07(1H, d, J=7.5Hz), 7.04(1H, dd, J=3.6 and 5.4Hz), 7.11(1H, d, J=3.9Hz), 7.24(1H, dd, J=1.2 and 3.6Hz), 7.28(1H, dd, J=1.2 and 5.4Hz), 7.42(1H, d J=3.9Hz).

[0356] IR(CHCl₃): 3511, 3445, 3428, 3113, 3073, 2667, 1708, 1643, 1521, 1498, 1455 cm⁻¹.

[0357] [α]_D²⁵+89.5±1.3° (c=1.005, MeOH)

[0358] Elemental Analysis (C₂₃H₂₇NO₃S₂•0.1H₂O) Calcd.(%): C, 64.04; H, 6.36; N, 3.25; S, 14.86 Found(%): C, 63.93; H, 6.39; N, 3.46; S, 14.61

[0359] mp.146–147° C.

[0360] 300MHz ¹H-NMR(CDCl₃) δ: 1.10(1H, m), 1.24–1.31(2H, m), 1.46–1.51(2H, m), 1.61–1.82(4H, m), 2.00–2.24(5H, m), 2.37(2H, t, J=7.2Hz), 2.37(3H, s), 2.56(1H, m), 3.85(1H, m), 5.31–5.45(2H, m), 6.06(1H, d, J=6.9Hz), 7.20 and 7.51(each 2H, each d, each J=9.0Hz), 7.21 and 7.48(each 1H, each d, each J=3.9Hz).

[0361] IR(CHCl₃): 3517, 3445, 3428, 1740, 1708, 1642, 1542, 1518, 1498, 1451 cm⁻¹.

[0362] [α]_D²⁶+89.3±1.3° (c=1.009, MeOH)

[0363] Elemental Analysis (C₂₆H₃₁NO₃S) Calcd.(%): C, 71.36; H, 7.14; N, 3.20; S, 7.33 Found(%): C, 71.51; H, 7.10; N, 3.20; S, 7.33

[0364] mp.110–116° C.

[0365] 300MHz ¹H-NMR(CDCl₃) δ: 1.10(1H, m), 1.24–1.31(2H, m), 1.46–1.51(2H, m), 1.61–1.83(4H, m), 2.00–2.25(5H, m), 2.37(2H, t, J=7.2Hz), 2.56(1H, m), 3.84(3H, s), 3.85(1H, m), 5.31–5.45(2H, m), 6.04(1H, d, J=7.5Hz), 6.93 and 7.55(each 2H, each d, each J=8.7Hz), 7.15 and 7.46(each 2H, each d, each J=4.2Hz).

[0366] IR(CHCl₃): 3515, 3445, 3428, 1740, 1708, 1640, 1608, 1541, 1499, 1453, 1178 cm⁻¹.

[0367] [α]_D²⁶+88.0±1.3° (c=1.010, MeOH)

[0368] Elemental Analysis (C₂₆H₃₁NO₄S) Calcd.(%): C, 68.85; H, 6.89; N, 3.09; S, 7.07 Found(%): C, 68.87; H, 6.82; N, 3.11; S, 7.19

[0369] mp.124–125° C.

[0370] 300MHz ¹H-NMR(CDCl₃) δ: 1.10(1H, m), 1.24–1.32(2H, m), 1.46–1.51(2H, m), 1.61–1.82(4H, m), 2.00–2.24(5H, m), 2.37(2H, t, J=7.2Hz), 2.56(1H, m), 3.85(1H, m), 5.32–5.45(2H, m), 6.06(1H, d, J=7.2Hz), 7.10(2H, t, J=8.7Hz), 6.19 and 7.47(each 1H, each d, each J=3.6Hz), 7.56–5.60(2H, m).

[0371] IR(CHCl₃): 3516, 3445, 3428, 2672, 1740, 1708, 1643, 1542, 1519, 1498, 1452 cm⁻¹.

[0372] [α]_D²⁶+83.3±1.2° (c=1.005, MeOH)

[0373] Elemental Analysis (C₂₅H₂₈FNO₃S) Calcd.(%): C, 68.00; H, 6.39; N, 3.17; F, 4.30; S, 7.26 Found(%): C, 67.90; H, 6.34; N, 3.25; F, 4.31; S, 7.20

[0374] 300MHz ¹H-NMR(CDCl₃) δ: 1.10(1H, m), 1.18–1.32(2H, m), 1.38–1.48(2H, m), 1.56–1.76(4H, m), 2.00–2.18(5H, m), 2.35(2H, t, J=7.2Hz), 2.53(1H, m), 3.81(1H, m), 5.31–5.43(2H, m), 6.32(1H, d, J=7.5Hz), 7.11(1H, dd, J=3.9 and 5.1Hz), 7.42 and 7.62(each 1H, each d, each J=3.9Hz), 7.70(1H, dd, J=1.5 and 5.1Hz), 7.74(1H, dd, J=1.5 and 3.9Hz).

[0375] IR(CHCl₃): 3516, 3442, 3378, 1708, 1655, 1530, 1504, 1336, 1153 cm⁻¹.

[0376] [α]_D²⁵+74.3±1.1° (c=1.000, MeOH)

[0377] Elemental Analysis (C₂₃H₂₇NO₅S₃•0.1H₂O) Calcd.(%): C, 55.76; H, 5.53; N, 2.83; S, 19.41 Found(%): C, 55.49; H, 5.64; N, 3.09; S, 19.32

[0378] mp.112–115° C.

[0379] 300MHz ¹H-NMR(CDCl₃) δ: 1.13–1.30(3H, m), 1.34–1.45(2H, m), 1.50–1.82(4H, m), 1.94–2.27(5H, m), 2.34(2H, t, J=7.2Hz), 2.56(1H, m), 3.74(1H, m), 5.22(2H, s), 5.31–5.50(2H, m), 6.64(1H, d, J=6.6Hz), 6.84(1H, d, J=3.9Hz), 6.93 and 7.05(each 1H, each s), 7.47(1H, d, J=3.9Hz), 7.66(1H, s).

[0380] IR(Nujol): 3339, 3102, 2464, 1691, 1635, 1622, 1551, 1288 cm⁻¹.

[0381] [α]_D²⁵+71.2±1.1° (c=1.005, MeOH)

[0382] Elemental Analysis (C₂₃H₂₉N₃O₃S) Calcd.(%): C, 64.61; H, 6.84; N, 9.83; S, 7.50 Found(%): C, 64.54; H, 6.85; N, 9.78; S, 7.42

[0383] 300MHz ¹H-NMR(CDCl₃) δ: 1.08(1H, m), 1.16–1.30(2H, m), 1.38–1.47(2H, m), 1.54–1.77(4H, m), 1.98–2.20(5H, m), 2.34(2H, t, J=7.2Hz), 2.52(1H, m), 3.79(1H, m), 5.30–5.42(2H, m), 5.47(2H, s), 6.16(1H, d, J=6.9Hz), 6.30(1H, t, J=2.1Hz), 6.94 and 7.41(each 1H, each d, each J=3.6Hz), 7.47 and 7.57(each 1H, each d, each J=2.1 Hz).

[0384] IR(CHCl₃): 3510, 3444, 3426, 1709, 1646, 1546, 1512 cm⁻¹.

[0385] [α]_D²⁵⁺68.6±1.1° (c=1.011, MeOH)

[0386] Elemental Analysis (C₂₃H₂₉N₃O₃S•0.1H₂O) Calcd.(%): C, 64.34; H, 6.85; N, 9.79; S, 7.47 Found(%): C, 64.10; H, 6.93; N, 9.90; S, 7.52

[0387] mp.126–128° C.

[0388] 300MHz ¹H-NMR(CDCl₃) δ: 1.12(1H, m), 1.18–1.33(2H, m), 1.40–1.50(2H, m), 1.55–1.78(4H, m), 2.00–2.21(5H, m), 2.54(1H, m), 3.87(1H, m), 5.30–5.44(2H, m), 6.43(1H, d, J=6.6Hz), 7.48–7.62(3H, m), 7.83–7.95(5H, m).

[0389] IR(Nujol): 3284, 3058, 2669, 1701, 1641, 1546, 1326, 1294, 1160 cm⁻¹.

[0390] [α]_D²⁵+77.2±1.2° (c=1.007, MeOH)

[0391] Elemental Analysis (C₂₇H₃₁NO₅S) Calcd.(%): C, 67.34; H, 6.49; N, 2.91; S, 6.66 Found(%): C, 67.20; H, 6.38; N, 2.88; S, 6.58

[0392] mp.103–107° C.

[0393] 300MHz ¹H-NMR(CDCl₃) δ: 1.14(1H, m), 1.18–1.33(2H, m), 1.40–1.50(2H, m), 1.54–1.77(4H, m), 2.00–2.20(5H, m), 2.34(2H, t, J=7.2Hz), 2.54(1H, m), 3.85(3H, s), 3.86(1H, m), 5.30–5.45(2H, m), 6.48(1H, d, J=6.9Hz), 6.96(2H, m), 7.81–7.91(6H, m).

[0394] IR(Nujol): 3273, 3067, 2669, 1702, 1639, 1560, 1548, 1323, 1301, 1274, 1156 cm⁻¹.

[0395] [α]_D²⁵+75.4±1.2° (c=1.002, MeOH)

[0396] Elemental Analysis (C₂₈H₃₃NO₆S) Calcd.(%): C, 65.73; H, 6.50; N, 2.74; S, 6.27 Found(%): C, 65.50; H, 6.46; N, 2.82; S, 6.25

[0397] 300MHz ¹H-NMR(CDCl₃) δ: 1.17(1H, m), 1.26–1.34(2H, m), 1.47–1.53(2H, m), 1.60–1.76(4H, m), 2.04–2.21(5H, m), 2.36(2H, t, J=7.2Hz), 2.60(1H, m), 3.91(1H, m), 5.32–5.47(2H, m), 6.46(1H, d, J=8.4Hz), 7.17(1H, dd, J=3.9 and 5.1Hz), 7.61(1H, dd, J=1.2 and 3.9Hz), 7.76(1H, dd, J=1.2 and 5.1Hz), 7.87(4H, s-like).

[0398] IR(CHCl₃): 3518, 3444, 2663, 1708, 1638, 1517, 1494, 1414 cm⁻¹.

[0399] [α]_D²⁵+86.6±1.3° (c=1.008, MeOH)

[0400] Elemental Analysis (C₂₆H₂₉NO₄S) Calcd.(%): C, 69.15; H, 6.47; N, 3.10; S, 7.10 Found(%): C, 68.86; H, 6.70; N, 3.15; S, 6.95

[0401] mp.144–145° C.

[0402] 300MHz ¹H-NMR(CDCl₃) δ: 1.20–2.54(16H, m), 2.62(1H, m), 3.69(3H, s), 5.35–5.56(2H, m), 6.36 and 7.17(each 2H, each t, each J=2.4Hz), 6.66(1H, d, J=6.3Hz), 8.05 and 8.07(each 1H, each d, each J=1.5Hz).

[0403] IR(Nujol): 3509, 3406, 3146, 3110, 1728, 1708, 1653, 1535, 1375, 1189, 1166 cm⁻¹.

[0404] [α]_D²⁵+67.9±1.1° (c=1.007, MeOH)

[0405] Elemental Analysis (C₂₃H₂₈N₂O₅S₂) Calcd.(%): C, 57.96; H, 5.92; N, 5.88; S, 13.45 Found(%): C, 58.19; H, 5.95; N, 5.75; S, 13.09

[0406] 300MHz ¹H-NMR(CDCl₃) δ: 1.22–2.57(16H, m), 2.68(1H, m), 3.66(3H, s), 5.37–5.63(2H, m), 6.20, 6.35, 6.74 and 6.87(each 2H, each t, each J=2.4Hz), 6.92(1H, d, J=5.4Hz), 8.27(1H, s).

[0407] IR(CHCl₃): 3402, 3143, 3108, 1725, 1710, 1650, 1516, 1375 cm⁻¹.

[0408] [α]_D²⁶+70.0±1.1° (c=1.006, MeOH)

[0409] Elemental Analysis (C₂₇H₃₁N₃O₅S₂•0.3H₂O) Calcd.(%): C, 59.28; H, 5.82; N, 7.68; S, 11.72 Found(%): C, 59.28; H, 5.77; N, 5.58; S, 11.68

[0410] 300MHz ¹H-NMR(CDCl₃) δ: 1.10(1H, m), 1.18–1.31(2H, m), 1.40–1.45(2H, m), 1.57–1.74(4H, m), 2.00–2.10(5H, m), 2.35(2H, t, J=7.2Hz), 2.38(3H, s), 2.52(1H, m), 3.80(1H, m), 5.31–5.43(2H, m), 5.99(1H, m), 6.20(1H, t, J=3.3Hz), 6.30(1H, d, J=6.9Hz), 7.18(1H, dd, J=1.8 and 3.3Hz), 7.40 and 7.53(each 1H, each d, each J=3.9Hz).

[0411] IR(CHCl₃): 3513, 3442, 3149, 3100, 1708, 1657, 1530, 1504, 1375, 1183, 1161 cm⁻¹.

[0412] [α]_D²⁷+70.3±1.5° (c=0.730, MeOH)

[0413] Elemental Analysis (C₂₄H₃₀N₂O₅S₂•0.4H₂O) Calcd.(%): C, 57.90; H, 6.24; N, 5.63; S, 12.88 Found(%): C, 58.08; H, 6.28; N, 5.77; S, 12.54

[0414] 300MHz ¹H-NMR(d₆-DMSO) δ: 1.06–1.59(9H, m), 1.93–2.07(5H, m), 2.21(2H, t, J=7.2Hz), 2.35(1H, m), 3.65(1H, m), 5.30–5.41(2H, m), 6.90 and 7.69(each 1H, each d, each J=4.2Hz), 7.55–7.64(3H, m), 7.99–8.04(3H, m), 11.73(1H, s), 12.01(1H, brs).

[0415] IR(KBr): 3562, 1708, 1616, 1564, 1523, 1454, 1295 cm⁻¹.

[0416] [α]_D²⁷+71.2±1.1° (c=1.000, MeOH)

[0417] Elemental Analysis (C₂₆H₃₀N₂O₄S•0.2H₂O) Calcd.(%): C, 66.42; H, 6.52; N, 5.96; S, 6.82 Found(%): C, 66.43; H, 6.32; N, 6.17; S, 6.75

[0418] 300MHz ¹H-NMR(d₆-DMSO) δ: 1.05–1.56(9H, m), 1.91–2.05(5H, m), 2.19(2H, t, J=7.2Hz), 2.29(1H, m), 3.56(1H, m), 5.28–5.38(2H, m), 6.54 and 7.56(each 1H, each d, each J=4.2Hz), 7.59–7.62(3H, m), 7.76–7.79(2H, m), 8.06(1H, d, J=6.9Hz), 11.10(1H, s), 11.99(1H, brs).

[0419] IR(KBr): 3384, 3084, 1707, 1616, 1553, 1523, 1459, 1350, 1322, 1161 cm⁻¹.

[0420] [α]_D²⁷+62.4±1.0° (c=1.005, MeOH)

[0421] Elemental Analysis (C₂₅H₃₀N₂O₅S₂•0.2H₂O) Calcd.(%): C, 59.31; H, 6.05; N, 5.53; S, 12.66 Found(%): C, 59.36; H, 5.75; N, 5.55; S, 12.38

[0422] 300MHz ¹H-NMR(CDCl₃) δ: 1.07(1H, m), 1.17–1.33(2H, m), 1.36–1.50(2H, m), 1.54–1.75(4H, m), 2.00–2.20(5H, m), 2.35(2H, t, J=7.2Hz), 2.45(3H, s), 2.52(1H, m), 3.80(1H, m), 5.31–5.43(2H, m), 6.12(1H, d, J=7.5Hz), 6.32 and 7.18(each 2H, each t, each J=2.4Hz), 7.22(1H, s).

[0423] IR(CHCl₃): 3316, 3442, 3145, 2668, 1708, 1657, 1545, 1509, 1455, 1375, 1190, 1165, 1057 cm⁻¹.

[0424] [α]_D²⁶+75.8±1.2° (c=1.002, MeOH)

[0425] Elemental Analysis (C₂₄H₃₀N₂O₅S₂•0.1H₂O) Calcd.(%): C, 58.54; H, 6.18; N, 5.69; S, 13.02 Found(%): C, 58.35; H, 6.29; N, 5.74; S, 12.92

[0426] 300MHz ¹H-NMR(CDCl₃) δ: 1.05(1H, m), 1.16–1.30(2H, m), 1.38–1.48(2H, m), 1.53–1.79(4H, m), 1.98–2.17(5H, m), 2.34(2H, t, J=7.2Hz), 2.50(1H, m), 3.79(1H, m), 5.30–5.42(2H, m), 6.00(1H, d, J=7.5Hz), 7.01(1H, dd, J=3.6 and 5.4Hz), 7.03(1H, d, J=3.9Hz), 7.29(1H, dd, J=1.2 and 3.6Hz), 7.33(1H, d, J=3.9) 7.43(1H, dd, J=1.2 and 5.4Hz).

[0427] IR(CHCl₃): 3517, 3444, 3426, 2670, 1708, 1645, 1530, 1499, 1421, 1318 cm⁻¹.

[0428] [α]_D²⁶+70.8±1.1° (c=1.018, MeOH)

[0429] Elemental Analysis (C₂₃H₂₇NO₃S₃) Calcd.(%): C, 59.84; H, 5.89; N, 3.03; S, 20.84 Found(%): C, 59.73; H, 5.99; N, 3.15; S, 20.70

[0430] 300MHz ¹H-NMR(CDCl₃) δ: 1.07(1H, m), 1.17–1.32(2H, m), 1.40–1.50(2H, m), 1.56–1.80(4H, m), 1.99–2.21(5H, m), 2.34(2H, t, J=7.2Hz), 2.54(1H, m), 3.85(1H, m), 5.29–5.42(2H, m), 6.20(1H, d, J=6.9Hz), 7.23–7.45(7H, m), 7.55(2H, d, J=8.1Hz).

[0431] IR(CHCl₃): 3516, 3447, 2667, 1708, 1651, 1596, 1514, 1481 cm⁻¹.

[0432] [α]_D²⁶+89.1±1.3° (c=1.006, MeOH)

[0433] Elemental Analysis (C₂₇H₃₁NO₃S•0.2H₂O) Calcd.(%): C, 71.56; H, 6.98; N, 3.09; S, 7.07 Found(%): C, 71.39; H, 6.97; N, 3.16; S, 6.94

[0434] 300MHz ¹H-NMR(CDCl₃) δ: 1.06(1H, m), 1.18–1.31(2H, m), 1.41–1.50(2H, m), 1.55–1.80(4H, m), 1.99–2.20(5H, m), 2.35(2H, t, J=7.2Hz), 2.52(1H, m), 3.82(1H, m), 5.31–5.43(2H, m), 5.97(1H, d, J=6.6Hz), 6.45(1H, d, J=4.2Hz), 7.11–7.20(3H, m), 7.28(1H, d, J=4.2Hz), 7.33–7.40(2H, m).

[0435] IR(CHCl₃): 3515, 3445, 3427, 2667, 1740, 1708, 1640, 1506, 1475 cm⁻¹.

[0436] [α]D²⁷+71.3±1.1° (c=1.002, MeOH)

[0437] Elemental Analysis (C₂₅H₂₉NO₄S) Calcd.(%): C, 68.31; H, 6.65; N, 3.19; S, 7.29 Found(%): C, 68.41; H, 6.87; N, 3.22; S, 7.35

[0438] 300MHz ¹H-NMR(CDCl₃) δ: 1.14(1H, m), 1.20–1.35(2H, m), 1.42–1.54(2H, m), 1.57–1.77(4H, m), 2.00–2.23(5H, m), 2.35(2H, t, J=7.2Hz), 2.58(1H, m), 3.88(1H, m), 5.32–5.46(2H, m), 6.31 and 7.19(each 2H, each t, each J=2.4Hz), 6.33(1H, d, J=7.5Hz), 7.77(1H, dd, J=1.8 and 8.4Hz), 7.77(1H, s), 7.87(1H, d, J=8.4Hz), 8.38(1H, d, J=1.8Hz).

[0439] IR(CHCl₃): 3514, 3442, 3422, 3144, 2670, 1708, 1654, 1525, 1375, 1193, 1171 cm⁻¹.

[0440] [α]_D²⁶+89.8±1.3° (c=1.000, MeOH)

[0441] Elemental Analysis (C₂₇H₃₀N₂O₅S₂) Calcd.(%): C, 61.58; H, 5.74; N, 5.32; S, 12.17 Found(%): C, 61.42; H, 5.86; N, 5.57; S, 11.98

[0442] mp.180–181° C.

[0443] 300MHz ¹H-NMR(CDCl₃) δ: 1.04(1H, m), 1.22–1.30(2H, m), 1.41–1.46(2H, m), 1.59–1.82(4H, m), 1.94–2.16(3H, m), 2.25–2.37(2H, m), 2.42(2H, t, J=6.9Hz), 2.52(1H, m), 2.52(3H, s), 3.79(1H, m), 5.41–5.59(2H, m), 5.73(1H, d, J=6.6Hz), 7.48–7.53(2H, m), 7.60(1H, m), 8.07–8.10(2H, m).

[0444] IR(Nujol): 3372, 3173, 3053, 2544, 1690, 1672, 1632, 1559, 1496, 1362, 1317 cm⁻¹.

[0445] [α]D²⁸+77.7±1.2° (c=1.007, MeOH)

[0446] Elemental Analysis (C₂₆H₃₁N₃O₄S) Calcd.(%): C, 64.84; H, 6.49; N, 8.72; S, 6.66 Found(%): C, 64.66; H, 6.31; N, 8.73; S, 6.65

[0447] 300MHz ¹H-NMR(d₆-DMSO) δ: 1.07(1H, m), 1.28–1.58(8H, m), 1.91–2.08(5H, m), 2.20(2H, t, J=7.2Hz), 2.31(3H, s), 2.32(1H, s), 3.96(1H, m), 5.28–5.40(2H, m), 7.52–7.62(3H, m), 7.80–7.83(2H, m), 7.94(1H, d, J=6.9Hz).

[0448] IR(Nujol): 3316, 3161, 3106, 2677, 1709, 1629, 1531, 1284, 1142 cm⁻¹.

[0449] [α]_D²⁷+76.2±1.2° (c=1.002, MeOH)

[0450] Elemental Analysis (C₂₅H₃₁N₃O₅S₂•0.1H₂O) Calcd.(%): C, 57.80; H, 6.05; N, 8.09; S, 12.34 Found(%): C, 57.59; H, 6.15; N, 8.10; S, 12.57

[0451] 300MHz ¹H-NMR(CDCl₃) δ: 1.28–1.31(2H, m), 1.47(2H, brs), 1.56–1.84(4H, m), 1.94–2.30(5H, m), 2.39(2H, t, J=6.9Hz), 2.62(1H, s), 2.63(3H, s), 3.77(1H, m), 5.35–5.67(2H, m), 6.42(1H, d, J=6.3Hz), 7.29–7.43(3H, m), 7.46(1H, s), 7.72(2H, d, J=7.2Hz).

[0452] IR(CHCl₃): 3517, 3421, 3350, 3150, 2538, 1708, 1651, 1590, 1512, 1474, 1442, 1164 cm⁻¹.

[0453] [ ]D²⁸+100.8±1.4° (c=1.002, MeOH)

[0454] Elemental Analysis (C₂₇H₃₁N₃O₃S•0.5H₂O) Calcd.(%): C, 66.64; H, 6.63; N, 8.63; S, 6.59 Found(%): C, 66.55; H, 6.59; N, 8.68; S, 6.76

[0455] 300MHz ¹H-NMR(CDCl₃) δ: 1.08(1H, m), 1.19–1.33(2H, m), 1.42–1.50(2H, m), 1.58–1.79(4H, m), 2.01–2.22(5H, m), 2.35(2H, t, J=7.2Hz), 2.55(1H, m), 3.86(1H, m), 4.37(2H, s), 5.30–5.43(2H, m), 6.19(1H, d, J=7.5Hz), 6.90(1H, dd, J=3.6 and 5.1Hz), 6.93(1H, m), 7.17(1H, dd, J=1.2 and 5.1Hz), 7.33 and 7.65(each 2H, each d, J=8.4Hz).

[0456] IR(CHCl₃): 3518, 3447, 2665, 1708, 1651, 1596, 1515, 1484 cm⁻¹.

[0457] [α]_D²⁶+82.4±1.4° (c=0.900, MeOH)

[0458] Elemental Analysis (C₂₆H₃₁NO₃S₂•0.1H₂O) Calcd.(%): C, 66.24; H, 6.67; N, 2.97; S, 13.60 Found(%): C, 66.14; H, 6.72; N, 2.96; S, 13.53

[0459] 300MHz ¹H-NMR(CDCl₃) δ: 1.16(1H, m), 1.21–1.34(2H, m), 1.43–1.52(2H, m), 1.57–1.76(4H, m), 2.04–2.22(5H, m), 2.35(2H, t, J=7.2Hz), 2.56(1H, m), 3.89(1H, m), 4.53(2H, s), 5.33–5.48(2H, m), 6.58(1H, d, J=6.9Hz), 6.83(1H, dd, J=1.2 and 3.9Hz), 6.93(1H, dd, J=3.9 and 5.1Hz), 7.28(1H, dd, J=1.2 and 5.1Hz), 7.65 and 7.81(each 2H, each d, J=8.4Hz).

[0460] IR(CHCl₃): 3518, 3442, 3373, 2666, 1708, 1658, 1516, 1483, 1323, 1153 cm⁻¹.

[0461] [α]_D²⁶+69.6±1.1° (c=1.003, MeOH)

[0462] Elemental Analysis (C₂₆H₃₁NO₅S₂•0.5H₂O) Calcd.(%): C, 61.15; H, 6.32; N, 2.74; S, 12.56 Found(%): C, 66.16; H, 6.25; N, 2.90; S, 12.57

[0463] 300MHz ¹H-NMR(CDCl₃) δ: 1.13(1H, m), 1.20–1.32(2H, m), 1.38–1.50(2H, m), 1.54–1.77(4H, m), 1.98–2.20(5H, m), 2.35(2H, t, J=7.2Hz), 2.53(1H, m), 3.80(1H, m), 5.31–5.46(2H, m), 6.47(1H, d, J=7.5Hz), 6.87(1H, dd, J=1.5 and 3.6Hz), 6.84(1H, dd, J=3.6 and 5.4Hz), 7.03(1H, dd, J=1.5 and 5.4Hz), 7.33 and 7.38(each 1H, each d, each J=3.9Hz), 7.90(1H, br).

[0464] IR(CHCl₃): 3510, 3440, 3358, 3109, 1708, 1647, 1533, 1505, 1364, 1331, 1161 cm⁻¹.

[0465] [α]₄₃₆²⁹+151.3±1.9° (c=1.010, MeOH) Elemental Analysis (C₂₃H₂₈N₂O₅S₃•0.1H₂O) Calcd.(%): C, 54.12; H, 5.57; N, 5.49; S, 18.84 Found(%): C, 53.84; H, 5.46; N, 5.38; S, 18.62

[0466] 300MHz ¹H-NMR(CDCl₃) δ: 1.20(1H, m), 1.26–1.38(2H, m), 1.42–1.52(2H, m), 1.57–1.76(4H, m), 2.00–2.24(5H, m), 2.34(2H, t, J=7.2Hz), 2.53(1H, m), 3.88(1H, m), 5.31–5.49(2H, m), 6.63(1H, dd, J=1.2 and 3.9Hz), 6.69(1H, d, J=7.5Hz), 6.77(1H, dd, J=3.9 and 5.4Hz), 6.98(1H, dd, J=1.2 and 5.4Hz), 7.66 and 7.76(each 2H, each d, each J=8.4Hz).

[0467] IR(CHCl₃): 3509, 3439, 3363, 3111, 1707, 1651, 1520, 1328, 1167 cm⁻¹.

[0468] [α]₄₃₆²⁹+155.7±2.0° (c=1.003, MeOH)

[0469] Elemental Analysis (C₂₅H₃₀N₂O₅S₃•0.3H₂O) Calcd.(%): C, 59.10; H, 6.07; N, 5.51; S, 12.62 Found(%): C, 59.00; H, 5.95; N, 5.51; S, 12.46

[0470] mp. 187–188° C.

[0471] 300MHz ¹H-NMR(d₆-DMSO) δ: 1.16–1.62(9H, m), 1.90–2.14(5H, m), 2.21(2H, t, J=7.2Hz), 2.38(1H, m), 3.66(1H, m), 5.27–5.41(2H, m), 7.10–7.15(1H, m), 7.34–7.39(2H, m), 7.42–7.75(2H, m), 7.91 and 7.99(each 1H, each d, each J=3.9Hz), 8.04(1H, d, J=6.6Hz), 10.32(1H, s), 12.02(1H, s).

[0472] IR(Nujol): 3316, 3075, 2678, 1704, 1635, 1614, 1544, 1323 cm⁻¹.

[0473] [α]D²⁸+83.3±1.2° (c=1.003, MeOH)

[0474] Elemental Analysis (C₂₆H₃₀N₂O₄S) Calcd.(%): C, 66.93; H, 6.48; N, 6.00; S, 6.87 Found(%): C, 67.04; H, 6.45; N, 5.98; S, 6.96

[0475] mp.192–194° C.

[0476] 300MHz ¹H-NMR(d₆-DMSO) δ: 1.16–1.62(9H, m), 1.90–2.14(5H, m), 2.21(2H, t, J=7.2Hz), 2.37(1H, m), 3.65(1H, m), 5.29–5.41(2H, m), 7.18–7.24(2H, m), 7.33–7.78(2H, m), 7.91 and 7.97(each 1H, each d, each J=3.9Hz), 8.04(1H, d, J=6.9Hz), 10.38(1H, s), 12.01(1H, s).

[0477] IR(Nujol): 3322, 3278, 3150, 3098, 3077, 2678, 1704, 1635, 1615, 1546, 1521, 1508, 1322 cm⁻¹.

[0478] [α]_D²⁸+83.3±1.2° (c=1.000, MeOH)

[0479] Elemental Analysis (C₂₆H₂₉FN₂O₄S) Calcd.(%): C, 64.44; H, 6.03; N, 5.78; F, 3.92; S, 6.62 Found(%): C, 64.36; H, 6.00; N, 5.81; F, 3.94; S, 6.46

[0480] mp.192–193° C.

[0481] 300MHz ¹H-NMR(d₆-DMSO) δ: 1.16–1.62(9H, m), 1.92–2.14(5H, m), 2.21(2H, t, J=7.2Hz), 2.37(1H, m), 3.66(1H, m), 3.75(3H, s), 5.30–5.41(2H, m), 6.94 and 7.63(each 2H, each d-like), 7.89 and 7.94(each 1H, each d, each J=3.9Hz), 8.38(1H, d, J=6.9Hz), 10.21(1H, s), 12.01(1H, s).

[0482] IR(Nujol): 3316, 3075, 2678, 1704, 1635, 1614, 1544, 1323 cm⁻¹.

[0483] [α]_D²⁷+81.6±1.2° (c=1.000, MeOH)

[0484] Elemental Analysis (C₂₇H₃₂N₂O₅S) Calcd.(%): C, 65.30; H, 6.49; N, 5.64; S, 6.46 Found(%): C, 65.19; H, 6.49; N, 5.45; S, 6.31

[0485] 300MHz ¹H-NMR(CDCl₃) δ: 1.14(1H, m), 1.18–1.32(2H, m), 1.40–1.78(6H, m), 1.94–2.20(5H, m), 2.35(2H, t, J=7.2Hz), 2.51(1H, m), 3.80(1H, m), 3.81(6H, s), 3.82(3H, s), 5.30–5.44(2H, m), 6.56(1H, d, J=7.2Hz), 6.97(2H, s), 7.47 and 7.58(each 1H, each d, each J=3.9Hz), 8.43(1H, s).

[0486] IR(CHCl₃): 3515, 3438, 3317, 1708, 1650, 1607, 1537, 1508, 1454, 1412, 1131 cm⁻¹.

[0487] [α]_D²⁷+75.8±1.2° (c=1.009, MeOH)

[0488] Elemental Analysis (C₂₉H₃₆N₂O₇S•0.4H₂O) Calcd.(%): C, 61.77; H, 6.58; N, 4.97; S, 5.69 Found(%): C, 61.74; H, 6.64; N, 4.89; S, 5.89

[0489] 300MHz ¹H-NMR(CDCl₃) δ: 1.10(1H, m), 1.20–1.33(2H, m), 1.43–1.52(2H, m), 1.57–1.78(4H, m), 2.00–2.21(5H, m), 2.36(2H, t, J=7.2Hz), 2.55(1H, m), 3.85(1H, m), 5.32–5.45(2H, m), 6.09(1H, d, J=6.9Hz), 6.32 and 7.00(each 2H, each t, each J=2.1Hz), 6.81 and 7.34(each 1H, each d, each J=3.9Hz).

[0490] IR(CHCl₃): 3515, 3445, 3109, 2678, 1740, 1708, 1642, 1507, 1489 cm⁻¹.

[0491] [α]_D²⁶+83.5±1.2° (c=1.007, MeOH)

[0492] Elemental Analysis (C₂₃H₂₈N₂O₃S) Calcd.(%): C, 66.96; H, 6.84; N, 6.79; S, 7.77 Found(%): C, 66.66; H, 6.74; N, 6.74; S, 7.61

[0493] 300MHz ¹H-NMR(CDCl₃) δ: 1.09(1H, m), 1.20–1.32(2H, m), 1.39–1.49(2H, m), 1.57–1.66(4H, m), 2.01–2.22(5H, m), 2.35(2H, t, J=7.2Hz), 2.56(1H, m), 3.88(1H, m), 3.95(2H, s), 5.30–5.44(2H, m), 6.27(1H, d, J=7.5Hz), 6.89–6.91(2H, m), 7.32(1H, dd, J=2.4 and 3.9Hz), 7.19 and 7.66(each 2H, each d, J=8.4Hz).

[0494] IR(CHCl₃): 3516, 3447, 2670, 1708, 1651, 1523, 1496 m⁻¹.

[0495] [α]_D²⁶+71.8±1.1° (c=1.016, MeOH)

[0496] Elemental Analysis (C₂₆H₃₁NO₃S₂•0.1H₂O) Calcd.(%): C, 66.24; H, 6.67; N, 2.97; S, 13.60 Found(%): C, 66.36; H, 6.67; N, 3.27; S, 13.62

[0497] mp. 135–136° C.

[0498] 300MHz ¹H-NMR(CDCl₃) δ: 1.12(1H, m), 1.22–1.33(2H, m), 1.43–1.51(2H, m), 1.59–1.78(4H, m), 2.03–2.22(5H, m), 2.35(2H, t, J=7.2Hz), 2.56(1H, m), 3.87(1H, m), 4.44(2H, s), 5.31–5.45(2H, m), 6.30(1H, d, J=7.2Hz), 7.08(1H, dd, J=3.9 and 5.1Hz), 7.23(2H, d, J=8.4Hz), 7.40(1H, dd, J=1.5 and 3.9Hz), 7.69–7.71(3H, m).

[0499] IR(CHCl₃): 3516, 3445, 3096, 2665, 1708, 1655, 1523, 1496, 1403, 1327, 1152, 1127 m⁻¹.

[0500] [α]_D²⁶+65.0±1.1° (c=1.000, MeOH)

[0501] Elemental Analysis (C₂₆H₃₁NO₅S₂•0.2H₂O) Calcd.(%): C, 61.81; H, 6.26; N, 2.77; S, 12.69 Found(%): C, 61.76; H, 6.20; N, 2.90; S, 12.57

[0502] mp.215–217° C.

[0503] 300MHz ¹H-NMR(d₆-DMSO) δ: 1.16–1.62(9H, m), 1.90–2.14(5H, m), 2.21(2H, t, J=7.2Hz), 2.38(1H, m), 3.66(1H, m), 5.29–5.41(2H, m), 6.91–6.94(2H, m), 7.05(1H, dd, J=2.4 and 4.2Hz), 7.93 and 7.96(each 1H, each d, each J=4.2Hz), 8.4391H, d, J=6.6Hz), 10.67(1H, br), 12.01(1H, br).

[0504] IR(Nujol): 3315, 3222, 3097, 3049, 2672, 1705, 1621, 1548, 1504, 1311 cm⁻¹.

[0505] [α]_D²⁷+88.2±1.3° (c=1.009, MeOH)

[0506] Elemental Analysis (C₂₄H₂₈N₂O₄S₂) Calcd.(%): C, 60.99; H, 5.97; N, 5.93; S, 13.57 Found(%): C, 60.94; H, 5.74; N, 5.91; S, 13.61

[0507] 300MHz ¹H-NMR(CDCl₃) δ: 1.09(1H, m), 1.18–1.31(2H, m), 1.40–1.47(2H, m), 1.57–1.73(4H, m), 2.00–2.12(5H, m), 2.31(2H, t, J=7.2Hz), 2.56(1H, m), 3.79(1H, m), 4.70(2H, s), 5.30–5.45(2H, m), 6.26–6.30(2H, m), 6.34(1H, d, J=6.9Hz), 7.22(1H, dd, J=1.8 and 3.3Hz), 7.41 and 7.62(each 1H, each d, each J=4.2Hz).

[0508] IR(CHCl₃): 3589, 3516, 3441, 3355, 3100, 1708, 1656, 1530, 1504, 1377, 1180, 1147 cm⁻¹.

[0509] [α]_D^26.5+70.8±1.1° (c=1.009, MeOH)

[0510] Elemental Analysis (C₂₄H₃₀N₂O₆S₂•0.2H₂O) Calcd.(%): C, 56.50; H, 6.01; N, 5.49; S, 12.57 Found(%): C, 56.43; H, 6.02; N, 5.61; S, 12.47

[0511] 300MHz ¹H-NMR(CDCl₃) δ: 1.06(1H, m), 1.16–1.30(2H, m), 1.38–1.50(2H, m), 1.54–1.77(4H, m), 1.98–2.18(5H, m), 2.35(2H, t, J=7.2Hz), 2.51(1H, m), 3.80(1H, m), 5.30–5.42(2H, m), 6.03(1H, d, J=7.2Hz), 7.04–7.06(2H, m), 7.32–7.35(2H, m), 7.37(1H, d, J=3.6Hz).

[0512] IR(CHCl₃): 3509, 3444, 3426, 3110, 2667, 1708, 1645, 1530, 1499, 1421 cm⁻¹.

[0513] [α]_D^26.5+69.5±1.1° (c=1.001, MeOH)

[0514] Elemental Analysis (C₂₃H₂₇NO₃S₃•0.1H₂O) Calcd.(%): C, 59.61; H, 5.92; N, 3.02; S, 20.76 Found(%): C, 59.66; H, 5.90; N, 3.15; S, 20.52

[0515] 300MHz ¹H-NMR(CDCl₃) δ: 1.10(1H, m), 1.17–1.32(2H, m), 1.38–1.48(2H, m), 1.54–1.77(4H, m), 2.00–2.20(5H, m), 2.35(2H, t, J=7.2Hz), 2.53(1H, m), 3.81(1H, m), 5.31–5.43(2H, m), 6.31(1H, d, J=7.2Hz), 7.37–7.44(3H, m), 7.61(1H, d, J=3.9Hz), 8.15(1H, dd, J=1.2 and 3.0Hz).

[0516] IR(CHCl₃): 3517, 3441, 3371, 3114, 1708, 1655, 1530, 1504, 1331, 1152 cm⁻¹.

[0517] [α]_D^26.5+73.9±1.1° (c=1.001, MeOH)

[0518] Elemental Analysis (C₂₃H₂₇NO₅S₃•0.3H₂O) Calcd.(%): C, 55.35; H, 5.57; N, 2.81; S, 19.28 Found(%): C, 55.47; H, 5.50; N, 2.80; S, 19.09

[0519] 300MHz ¹H-NMR(CDCl₃) δ: 1.05(1H, m), 1.16–1.30(2H, m), 1.38–1.48(2H, m), 1.54–1.77(4H, m), 1.98–2.17(5H, m), 2.34(2H, t, J=7.2Hz), 2.46(3H, d, J=0.9Hz), 2.50(1H, m), 3.79(1H, m), 5.29–5.41(2H, m), 5.99(1H, d, J=7.2Hz), 6.67(1H, m), 6.99, 7.10 and 7.32(each 1H, each d, each J=3.9Hz).

[0520] IR(CHCl₃): 3517, 3445, 3426, 2668, 1708, 1644, 1530, 1499, 1420, cm⁻¹.

[0521] [α]_D^26.5+66.1±1.1° (c=1.002, MeOH)

[0522] Elemental Analysis (C₂₄H₂₉NO₃S₃•0.1H₂O) Calcd.(%): C, 60.37; H, 6.16; N, 2.93; S, 20.15 Found(%): C, 60.21; H, 6.10; N, 2.90; S, 20.45

[0523] 300MHz ¹H-NMR(CDCl₃) δ: 1.11(1H, m), 1.18–1.32(2H, m), 1.38–1.50(2H, m), 1.54–1.74(4H, m), 2.00–2.20(5H, m), 2.35(2H, t, J=7.2Hz), 2.53(4H, d and m, J=0.6Hz), 3.80(1H, m), 5.31–5.43(2H, m), 6.34(1H, d, J=6.6Hz), 6.77(1H, m), 7.41, 7.55 and 7.58(each 1H, each d, each J=3.9Hz).

[0524] IR(CHCl₃): 3511, 3442, 3373, 3096, 1708, 1655, 1530, 1504, 1436, 1335, 1152 cm⁻¹.

[0525] [α]_D^26.5+73.0±1.1° (c=1.002, MeOH)

[0526] Elemental Analysis (C₂₄H₂₉NO₅S₃•0.3H₂O) Calcd.(%): C, 56.18; H, 5.81; N, 2.73; S, 18.75 Found(%): C, 56.26; H, 5.74; N, 2.65; S, 18.50

[0527] 300MHz ¹H-NMR(CDCl₃) δ: 1.17(1H, m), 1.24–1.36(2H, m), 1.37–1.82(6H, m), 2.01–2.23(5H, m), 2.36(2H, t, J=7.2Hz), 2.51(1H, m), 3.83(1H, m), 5.31–5.45(2H, m), 7.17(1H, dd, J=3.9 and 5.4Hz), 7.36(1H, d, J=7.8Hz), 7.47(1H, dd, J=1.5 and 3.9Hz), 7.66(1H, dd, J=1.5 and 5.4Hz).

[0528] IR(CHCl₃): 3514, 3404, 3121, 1709, 1657, 1544, 1488, 1425 cm⁻¹.

[0529] [α]_D²⁵+73.2±2.2° (c=0.518, MeOH)

[0530] Elemental Analysis (C₂₂H₂₆N₂O₃S₃•0.2H₂O) Calcd.(%): C, 56.67; H, 5.71; N, 6.01; S, 20.63 Found(%): C, 56.55; H, 5.71; N, 6.03; S, 20.93

[0531] 300MHz ¹H-NMR(CDCl₃) δ: 1.07(1H, m), 1.20–1.32(2H, m), 1.43–1.48(2H, m), 1.57–1.82(4H, m), 2.02(1H, d, J=3.3Hz), 2.00–2.20(5H, m), 2.35(2H, t, J=7.2Hz), 2.55(1H, m), 3.86(1H, m), 4.01(2H, s), 5.29–5.43(2H, m), 6.17(1H, d, J=7.2Hz), 7.15–7.31(7H, m), 7.67(2H, d, J=8.1Hz).

[0532] IR(CHCl₃): 3517, 3447, 2669, 1708, 1651, 1523, 1495 cm⁻¹.

[0533] [α]_D²⁵+77.9±1.2° (c=1.016, MeOH)

[0534] Elemental Analysis (C₂₈H₃₃NO₃) Calcd.(%): C, 77.93; H, 7.71; N, 3.25 Found(%): C, 77.65; H, 7.93; N, 3.32

[0535] 300MHz ¹H-NMR(CDCl₃) δ: 1.08(1H, m), 1.21–1.31(2H, m), 1.44–1.49(2H, m), 1.58–1.82(4H, m), 2.00–2.20(5H, m), 2.35(2H, t, J=7.2Hz), 2.56(1H, m), 3.87(1H, m), 4.19(2H, s), 5.30–5.43(2H, m), 6.19(1H, d, J=7.2Hz), 6.80(1H, m), 6.93(1H, dd, J=2.6 and 5.1Hz), 7.16(1H, dd, J=1.5 and 5.1Hz), 7.30 and 8.69(each 2H, each d, each J=8.1Hz).

[0536] IR(CHCl₃): 3510, 3446, 2664, 1708, 1651, 1523, 1496 cm⁻¹.

[0537] [α]_D²⁵+73.2±1.1° (c=1.009, MeOH)

[0538] Elemental Analysis (C₂₆H₃₁NO₃S) Calcd.(%): C, 71.36; H, 7.14; N, 3.20; S, 7.33 Found(%): C, 71.48; H, 7.05; N, 3.29; S, 7.13

[0539] 300MHz ¹H-NMR(CDCl₃) δ: 1.07(1H, m), 1.19–1.31(2H, m), 1.43–1.48(2H, m), 1.58–1.81(4H, m), 2.00–2.17(5H, m), 2.34(2H, t, J=7.2Hz), 2.55(1H, m), 3.87(1H, m), 3.98(2H, s), 5.30–5.43(2H, m), 6.19(1H, d, J=7.2Hz), 6.93–7.00(2H, m), 7.09–7.13(2H, m), 7.22 and 7.70(each 2H, each d, each J=8.4Hz).

[0540] IR(CHCl₃): 3516, 3447, 2664, 1709, 1651, 1612, 1522, 1509, 1496, cm⁻¹.

[0541] [α]_D²⁵+71.6±1.1° (c=1.019, MeOH)

[0542] Elemental Analysis (C₂₈H₃₂FNO₃) Calcd.(%): C, 74.81; H, 7.17; N, 3.12; F, 4.23 Found(%): C, 74.66; H, 7.19; N, 3.13; F, 4.10

[0543] 300MHz ¹H-NMR(CDCl₃) δ: 1.08(1H, m), 1.20–1.31(2H, m), 1.44–1.49(2H, m), 1.58–1.82(4H, m), 2.00–2.22(5H, m), 2.35(2H, t, J=7.2Hz), 2.56(1H, m), 3.87(1H, m), 4.02(2H, s), 5.30–5.43(2H, m), 6.18(1H, d, J=7.2Hz), 6.88(1H, dd, J=1.5 and 4.8Hz), 6.92(1H, m), 7.25–7.28(3H, m), 7.68(2H, d, J=8.1Hz).

[0544] IR(CHCl₃): 3516, 3446, 2668, 1709, 1651, 1612, 1523, 1496 cm⁻¹.

[0545] [α]_D²⁵+72.7±1.1° (c=1.014, MeOH)

[0546] Elemental Analysis (C₂₆H₃₁NO₃S•0.1H₂O) Calcd.(%): C, 71.07; H, 7.16; N, 3.18; S, 7.30 Found(%): C, 70.90; H, 7.08; N, 3.21; S, 7.46

[0547] mp. 103–105° C.

[0548] 300MHz ¹H-NMR(CDCl₃) δ: 1.05(1H, m), 1.19–1.29(2H, m), 1.42–1.47(2H, m), 1.58–1.81(4H, m), 2.00–2.15(5H, m), 2.35(2H, t, J=7.2Hz), 2.52(1H, m), 3.82(1H, m), 4.16(2H, s), 5.30–5.43(2H, m), 5.97(1H, d, J=7.5Hz), 6.79(1H, dt, J=0.9 and 3.9Hz), 6.96(1H, dd, J=1.5 and 4.8Hz), 7.05(1H, m), 7.28(1H, dd, J=3.0 and 4.8Hz), 7.37(1H, d, J=3.9Hz).

[0549] IR(CHCl₃): 3516, 3445, 3427, 2670, 1708, 1642, 1544, 1507 cm⁻¹.

[0550] [α]_D²⁵+67.3±1.1° (c=1.002, MeOH)

[0551] Elemental Analysis (C₂₄H₂₉NO₃S₂•0.3H₂O) Calcd.(%): C, 64.20; H, 6.64; N, 3.12; S, 14.28 Found(%): C, 64.29; H, 6.49; N, 3.10; S, 14.11

[0552] 300MHz ¹H-NMR(CDCl₃) δ: 1.07(1H, m), 1.20–1.29(2H, m), 1.40–1.49(2H, m), 1.56–1.89(4H, m), 2.00–2.25(5H, m), 2.32–2.38(2H, m), 2.51(1H, m), 3.80(1H, m), 5.04(2H, s), 5.27–5.41(2H, m), 5.90(1H, d, J=6.6Hz), 6.38(1H, m), 6.63(1H, t, J=2.4Hz), 7.14–7.17(2H, m), 7.29–7.35(4H, m).

[0553] IR(CHCl₃): 3510, 3448, 2663, 1736, 1709, 1636, 1555, 1497 cm⁻¹.

[0554] [α]_D²⁵+60.8±1.0° (c=1.003, MeOH)

[0555] Elemental Analysis (C₂₆H₃₂N₂O₃•0.3H₂O) Calcd.(%): C, 73.62; H, 7.70; N, 6.60 Found(%): C, 73.68; H, 7.62; N, 6.73

[0556] 300MHz ¹H-NMR(CDCl₃) δ: 1.06(1H, m), 1.20–1.29(2H, m), 1.40–1.48(2H, m), 1.56–1.87(4H, m), 2.00–2.24(5H, m), 2.32–2.38(2H, m), 2.50(1H, m), 3.80(1H, m), 5.19(2H, s), 5.27–5.41(2H, m), 5.90(1H, d, J=7.5Hz), 6.37(1H, dd, J=2.1 and 3.0Hz), 6.67(1H, t, J=2.4Hz), 6.95–6.98(2H, m), 7.27(1H, dd, J=1.8 and 4.5Hz), 7.31(1H, dd, J=1.8 and 2.1Hz).

[0557] IR(CHCl₃): 3513, 3448, 2661, 1709, 1637, 1555, 1497 cm⁻¹.

[0558] [α]_D²⁵+59.4±1.0° (c=1.011, MeOH)

[0559] Elemental Analysis (C₂₄H₃₀N₂O₃S•0.2H₂O) Calcd.(%): C, 67.01; H, 7.12; N, 6.51; S, 7.45 Found(%): C, 67.07; H, 7.03; N, 6.62; S, 7.55

[0560] 300MHz ¹H-NMR(CDCl₃) δ: 1.06(1H, m), 1.23–1.26(2H, m), 1.39–1.48(2H, m), 1.57–1.82(4H, m), 2.00–2.16(5H, m), 2.34(2H, t, J=7.2Hz), 2.50(1H, m), 3.82(1H, m), 5.03(2H, s), 5.27–5.42(2H, m), 5.98(1H, brs), 6.40(1H, m), 6.91(1H, dd, J=1.2 and 4.8Hz), 7.08(1H, brs), 7.28–7.31(2H, m).

[0561] IR(CHCl₃): 3516, 3448, 3108, 2663, 1736, 1709, 1636, 1555, 1497 cm⁻¹.

[0562] [α]_D²⁵+59.8±1.0° (c=1.008, MeOH)

[0563] Elemental Analysis (C₂₄H₃₀N₂O₃S•0.2H₂O) Calcd.(%): C, 67.01; H, 7.12; N, 6.51; S, 7.45 Found(%): C, 67.26; H, 7.06; N, 6.61; S, 7.55

[0564] 300MHz ¹H-NMR(CDCl₃) δ: 1.08(1H, m), 1.18–1.28(2H, m), 1.38–1.43(2H, m), 1.54–1.78(4H, m), 1.96–2.23(5H, m), 2.36(2H, dt, J=1.8 and 6.9Hz), 2.52(1H, m), 3.77(1H, m), 5.30–5.45(2H, m), 6.07(1H, d, J=6.9Hz), 6.58(1H, dd, J=1.5 and 3.3Hz), 7.14(1H, dd, J=2.1 and 3.3Hz), 7.51–7.57(2H, m), 7.65(1H, m), 7.77(1H, t, J=2.1Hz), 7.88–7.92(2H, m).

[0565] IR(CHCl₃): 3510, 3444, 3144, 1732, 1708, 1651, 1570, 1509, 1382, 1176 cm⁻¹.

[0566] [α]_D²⁴+55.9±0.9° (c=1.013, MeOH)

[0567] Elemental Analysis (C₂₅H₃₀N₂O₅S•0.3H₂O) Calcd.(%): C, 63.08; H, 6.48; N, 5.88; S, 6.74 Found(%): C, 63.24; H, 6.27; N, 6.03; S, 6.74

[0568] 300MHz ¹H-NMR(CDCl₃) δ: 1.06(1H, m), 1.18–1.29(2H, m), 1.39–1.47(2H, m), 1.56–1.78(4H, m), 1.98–2.18(5H, m), 2.35(2H, t, J=7.2Hz), 2.52(1H, m), 3.81(1H, m), 4.33(2H, s), 5.29–5.42(2H, m), 6.03(1H, d, J=7.5Hz), 6.84(1H, d, J=3.9Hz), 6.90(1H, m), 6.95(1H, dd, J=3.6 and 5.1Hz), 7.19(1H, dd, J=1.2 and 5.1Hz), 7.38(1H, d, J=3.9Hz).

[0569] IR(CHCl₃): 3510, 3554, 3427, 1708, 1643, 1544, 1507 m⁻¹.

[0570] [α]_D²⁷+70.1±1.10 (c=1.010, MeOH)

[0571] Elemental Analysis (C₂₄H₂₉NO₃S₂•0.1H₂O) Calcd.(%): C, 64.72; H, 6.61; N, 3.14; S, 14.40 Found(%): C, 64.83; H, 6.60; N, 3.31; S, 14.46

[0572] 300MHz ¹H-NMR(CDCl₃) δ: 1.09(1H, m), 1.20–1.27(2H, m), 1.40–1.44(2H, m), 1.56–1.78(4H, m), 2.00–2.19(5H, m), 2.36(2H, d, 7.2Hz), 2.51(1H, m), 3.78(1H, m), 5.30–5.44(2H, m), 6.13(1H, d, J=6.9Hz), 6.59(1H, dd, J=1.5 and 3.3Hz), 7.10(1H, dd, J=3.6 and 5.1Hz), 7.16(1H, dd, J=2.1 and 3.3Hz), 7.69–7.76(3H, m).

[0573] IR(CHCl₃): 3510, 3444, 3143, 1708, 1651, 1571, 1508, 1387, 1179 cm⁻¹.

[0574] [α]_D²⁴+56.0±1.0° (c=1.005, MeOH)

[0575] Elemental Analysis (C₂₃H₂₈N₂O₅S₂•0.2H₂O) Calcd.(%): C, 57.53; H, 5.96; N, 5.83; S, 13.35 Found(%): C, 57.54; H, 6.07; N, 5.93; S, 12.91

[0576] 300MHz ¹H-NMR(CDCl₃) δ: 1.16(1H, m), 1.26–1.37(2H, m), 1.40–1.81(6H, m), 2.04–2.25(5H, m), 2.36(2H, t, J=7.2Hz), 2.53(1H, m), 3.87(1H, m), 5.32–5.46(2H, m), 6.37(2H, t, J=2.1Hz), 7.31(1H, d, J=7.5Hz), 7.33(2H, t, J=2.1Hz), 7.82(1H, m).

[0577] IR(CHCl₃): 3512, 3408, 3127, 1708, 1658, 1540, 1525, 1493, 1341 m⁻¹.

[0578] [α]_D²⁵+88.2±1.3° (c=1.003, MeOH)

[0579] Elemental Analysis (C₂₂H₂₇N₃O₃S•0.1H₂O) Calcd.(%): C, 63.62; H, 6.60; N, 10.12; S, 7.72 Found(%): C, 63.72; H, 6.45; N, 9.99; S, 7.75

[0580] 300MHz ¹H-NMR(CDCl₃) δ: 1.07(1H, m), 1.18–1.30(2H, m), 1.39–1.48(2H, m), 1.57–1.78(4H, m), 2.01–2.22(5H, m), 2.35(2H, t, J=7.2Hz), 2.52(1H, m), 3.80(1H, m), 5.30–5.43(2H, m), 6.11(1H, m), 6.98(1H, dd, J=3.6 and 5.4Hz), 7.24(1H, dd, J=1.2 and 3.6Hz), 7.38(1H, dd, J=1.2 and 5.4Hz), 7.43(1H, d, J=1.5Hz), 7.85(1H, d, J=1.5Hz).

[0581] IR(CHCl₃): 3510, 3445, 3108, 1708, 1650, 1535, 1498 m⁻¹.

[0582] [α]_D²⁵+70.7±1.1° (c=1.004, MeOH)

[0583] Elemental Analysis (C₂₃H₂₇NO₃S₃•0.3H₂O) Calcd.(%): C, 59.15; H, 5.96; N, 3.00; S, 20.60 Found(%): C, 59.06; H, 5.66; N, 3.07; S, 20.87

[0584] 300MHz ¹H-NMR(CDCl₃) δ: 1.20–2.52(16H, m), 2.61(1H, m), 3.72(1H, m), 5.34–5.55(2H, m), 6.66(1H, d, J=6.3Hz), 71.2(1H, m), 7.71(1H, m), 7.75(1H, m), 8.29(1H, m), 8.37(1H, brs).

[0585] IR(CHCl₃): 3512, 3405, 3096, 1726, 1710, 1653, 1542, 1505, 1402, 1329, 1152 m⁻¹.

[0586] [α]_D²⁵+65.4±1.1° (c=1.005, MeOH)

[0587] Elemental Analysis (C₂₃H₂₇NO₅S₃•0.2H₂O) Calcd.(%): C, 55.55; H, 5.55; N, 2.82; S, 19.35 Found(%): C, 55.47; H, 5.54; N, 3.09; S, 19.21

[0588] mp.103–104° C.

[0589] 300MHz ¹H-NMR(CDCl₃) δ: 1.09(1H, m), 1.23–1.31(2H, m), 1.45–1.50(2H, m), 1.60–1.80(4H, m), 2.00–2.23(5H, m), 2.37(2H, t, J=7.2Hz), 2.55(1H, m), 3.85(1H, m), 5.31–5.45(2H, m), 6.05(1H, d, J=7.5Hz), 6.98 and 7.04(each 1H, each d, each J=16.2Hz), 6.97(1H, d, J=3.9Hz), 7.25–7.33(3H, m), 7.41(1H, d, J=3.9Hz).

[0590] IR(CHCl₃): 3511, 3445, 3428, 2665, 1708, 1641, 1538, 1519, 1499 cm⁻¹.

[0591] [α]_D²⁴+77.8±1.2° (c=1.007, MeOH)

[0592] Elemental Analysis (C₂₅H₂₉NO₃S₂•0.25AcOEt) Calcd.(%): C, 65.38; H, 6.54; N, 2.93; S, 13.43 Found(%): C, 65.64; H, 6.62; N, 2.95; S, 13.26

[0593] 300MHz ¹H-NMR(CDCl₃) δ: 1.05(1H, m), 1.20–1.30(2H, m), 1.41–1.46(2H, m), 1.59–1.80(4H, m), 2.00–2.20(5H, m), 2.35(2H, t, J=7.2Hz), 2.52(1H, m), 3.80(1H, m), 5.30–5.43(2H, m), 5.94(1H, d, J=6.9Hz), 6.57(2H, s), 6.94(1H, d, J=3.9Hz), 7.03(1H, dd, J=1.5 and 4.5Hz), 7.29(1H, s), 7.30(1H, m), 7.34(1H, d, J=3.9Hz).

[0594] IR(CHCl₃): 3511, 3445, 3427, 2670, 1708, 1642, 1536, 1518, 1500 cm⁻¹.

[0595] [α]_D²⁴+62.8±1.0° (c=1.003, MeOH)

[0596] Elemental Analysis (C₂₅H₂₉NO₃S₂•0.2AcOEt) Calcd.(%): C, 65.48; H, 6.52; N, 2.96; S, 13.55 Found(%): C, 65.36; H, 6.47; N, 2.13; S, 13.58

[0597] 300MHz ¹H-NMR(CDCl₃) δ: 1.06(1H, m), 1.17–1.32(2H, m), 1.38–1.50(2H, m), 1.56–1.80(4H, m), 1.98–2.20(5H, m), 2.35(2H, t, J=7.2Hz), 2.44(3H, d, J=0.9Hz), 2.52(1H, m), 3.80(1H, m), 5.30–5.43(2H, m), 5.99(1H, d, J=7.5Hz), 5.99(1H, d, J=7.5Hz), 6.70(1H, m), 7.03(1H, d, J=3.9Hz), 7.10(1H, d, J=1.5Hz), 7.36(1H, d, J=3.9Hz).

[0598] IR(CHCl₃): 3510, 3445, 3426, 2671, 1708, 1644, 1530, 1499, 1420, 1318 cm⁻¹.

[0599] [α]_D²⁵+69.1±1.1° (c=1.018, MeOH)

[0600] Elemental Analysis (C₂₄H₂₉NO₃S₃) Calcd.(%): C, 60.60; H, 6.14; N, 2.94; S, 20.22 Found(%): C, 60.49; H, 6.26; N, 2.98; S, 20.25

[0601] 300MHz ¹H-NMR(CDCl₃) δ: 1.10(1H, m), 1.18–1.32(2H, m), 1.38–1.50(2H, m), 1.54–1.77(4H, m), 2.00–2.20(5H, m), 2.36(2H, t, J=7.2Hz), 2.47(3H, d, J=0.9Hz), 2.53(1H, m), 3.81(1H, m), 5.31–5.44(2H, m), 6.30(1H, d, J=7.2Hz), 7.03(1H, m), 7.42 and 7.59(each 1H, each d, each J=3.9Hz), 7.90(1H, d, J=1.5Hz).

[0602] IR(CHCl₃): 3517, 3441, 3370, 3115, 2671, 1708. 1655, 1530, 1504, 1442, 1328, 1156, 1142 cm⁻¹.

[0603] [α]_D²⁴+7.6±1.1° (c=1.018, MeOH)

[0604] Elemental Analysis (C₂₄H₂₉NO₅S₃•0.2H₂O) Calcd.(%): C, 56.38; H, 5.80; N, 2.74; S, 18.81 Found(%): C, 56.28; H, 5.74; N, 2.79; S, 18.92

[0605] 300MHz ¹H-NMR(CDCl₃) δ: 1.09(1H, m), 1.21–1.28(2H, m), 1.42–1.47(2H, m), 1.57–1.74(4H, m), 2.00–2.18(5H, m), 2.35(2H, t, J=7.2Hz), 2.53(1H, m), 3.82(1H, 5.30–5.43(2H, m), 6.15(1H, d, J=7.5Hz), 6.51 and 6.68(each 1H, each d, J=11.7Hz), 6.98(1H, dd, J=3.6 and 5.1Hz), 7.06(1H, dd, J=0.9 and 3.9Hz), 7.13(1H, dt, J=0.9 and 3.6Hz), 7.25(1H, dd, J=0.9 and 5.1Hz), 7.41(1H, d, J=3.9Hz).

[0606] IR(CHCl₃): 3510, 3445, 3427, 2665, 1708, 1643, 1535, 1501 cm⁻¹.

[0607] [α]_D²⁴+68.6±1.1° (c=1.006, MeOH)

[0608] Elemental Analysis (C₂₅H₂₉NO₃S₂•0.2H₂O) Calcd.(%): C, 65.45; H, 6.45; N, 3.05; S, 13.98 Found(%): C, 65.44; H, 6.37; N, 3.28; S, 13.82

[0609] mp.107–108° C.

[0610] 300MHz ¹H-NMR(CDCl₃) δ: 1.09(1H, m), 1.26–1.32(2H, m), 1.45–1.50(2H, m), 1.60–1.81(4H, m), 2.01–2.23(5H, m), 2.37(2H, t, J=7.2Hz), 2.55(1H, m), 3.84(1H, m), 5.31–5.45(2H, m), 6.03(1H, d, J=7.5Hz), 6.97 and 7.14(each 1H, each d, J=15.9Hz), 6.97(1H, d, J=3.9Hz), 7.01(1H, dd, J=3.6 and 5.4Hz), 7.08(1H, d, J=3.6Hz), 7.23(1H, d, J=5.4Hz), 7.40(1H, d, J=3.9Hz).

[0611] IR(CHCl₃): 3517, 3445, 3428, 2670, 1708, 1641, 1536, 1518, 1500 cm⁻¹.

[0612] [α]_D²⁴+85.0±1.2° (c=1.009, MeOH)

[0613] Elemental Analysis (C₂₅H₂₉NO₃S₂•0.15AcOEt) Calcd.(%): C, 65.58; H, 6.49; N, 2.99; S, 13.68 Found(%): C, 65.88; H, 6.74; N, 2.98; S, 13.35

[0614] 300MHz ¹H-NMR(CDCl₃) δ: 1.07(1H, m), 1.19–1.30(2H, m), 1.42–1.50(2H, m), 1.57–1.79(4H, m), 2.01–2.24(5H, m), 2.36(2H, t, J=7.2Hz), 2.53(1H, m), 3.82(1H, m), 4.10(sH, s), 5.31–5.44(2H, m), 6.03(1H, d, J=7.2Hz), 6.70(1H, d, J=3.6Hz), 6.95(1H, dd, J=3.6 and 5.4Hz), 7.03(1H, dd, J=1.5 and 3.6Hz), 7.30(1H, d, J=3.6Hz), 7.36(1H, dd, J=1.5 and 5.4Hz).

[0615] IR(CHCl₃): 3518, 3445, 3427, 1708, 1644, 1542, 1507 cm⁻¹.

[0616] [α]_D^24.5+65.0±1.0° (c=1.008, MeOH)

[0617] Elemental Analysis (C₂₄H₂₉NO₃S₃•0.4H₂O) Calcd.(%): C, 59.69; H, 6.22; N, 2.90; S, 19.92 Found(%): C, 59.40; H, 5.98; N, 2.95; S, 20.06

[0618] 300MHz ¹H-NMR(CDCl₃) δ: 1.11(1H, m), 1.21–1.31(2H, m), 1.42–1.49(2H, m), 1.58–1.76(4H, m), 2.01–2.21(5H, m), 2.36(2H, t, J=7.2Hz), 2.53(1H, m), 3.81(1H, m), 4.60(sH, s), 5.32–5.45(2H, m), 6.18(1H, d, J=7.2Hz), 6.91(1H, d, J=3.9Hz), 7.12(1H, dd, J=3.9 and 5.1Hz), 7.40(1H, d, J=3.9Hz), 7.52(1H, dd, J=1.2 and 3.9Hz), 7.72(1H, dd, J=1.2 and 5.1Hz).

[0619] IR(CHCl₃): 3517, 3444, 3425, 3097, 1708, 1648, 1524, 1508, 1402, 1328, 1147 cm⁻¹.

[0620] [α]_D^24.5+61.5±1.0° (c=1.008, MeOH)

[0621] Elemental Analysis (C₂₄H₂₉NO₃S₃•0.4H₂O) Calcd.(%): C, 55.98; H, 5.83; N, 2.72; S, 18.68 Found(%): C, 55.77; H, 5.71; N, 2.84; S, 18.73

[0622] 300MHz ¹H-NMR(CDCl₃) δ: 1.07(1H, m), 1.19–1.31(2H, m), 1.41–1.49(2H, m), 1.57–1.78(4H, m), 2.00–2.21(5H, m), 2.36(2H, t, J=7.2Hz), 2.53(1H, m), 3.81(1H, m), 4.23(sH, s), 5.31–5.44(2H, m), 6.00(1H, d, J=7.2Hz), 6.82(1H, m), 6.88(1H, dd, J=3.6 and 5.1Hz), 6.92(1H, d, J=3.6Hz), 7.21(1H, dd, J=1.2 and 5.1Hz), 7.33(1H, d, J=3.6Hz).

[0623] IR(CHCl₃): 3514, 3444, 3427, 2665, 1709, 1645, 1529, 1498, 1421, 1317 cm⁻¹.

[0624] [α]_D²⁴+67.1±1.1° (c=1.006, MeOH)

[0625] Elemental Analysis (C₂₄H₂₉NO₃S₃•0.1H₂O) Calcd.(%): C, 60.37; H, 6.16; N, 2.90; S, 20.15 Found(%): C, 60.46; H, 6.14; N, 2.96; S, 20.02

[0626] 300MHz ¹H-NMR(CDCl₃) δ: 1.09–1.32(3H, m), 1.38–1.48(2H, m), 1.53–1.79(4H, m), 1.96–2.20(5H, m), 2.34(2H, t, J=7.2Hz), 2.54(4H, d and m, J=0.6Hz), 3.79(1H, m), 5.30–5.45(2H, m), 6.48 and 6.51(total 1H, each d, J=7.8 and 7.5Hz), 7.12(1H, dd, J=3.9 and 5.1Hz), 7.42 and 7.43(total 1H, each d, each J=3.9Hz), 7.52 and 7.53(total 1H, each d, each J=3.9Hz), 7.58(1H, m), 7.69(1H, dd, J=1.2 and 5.1Hz).

[0627] IR(CHCl3): 3509, 3443, 3425, 3092, 2666, 1708, 1650, 1532, 1503, 1403, 1322 cm⁻¹.

[0628] [α]_D²³+70.4±1.1° (c=1.007, MeOH)

[0629] Elemental Analysis (C₂₃H₂₇NO₄S₃•0.4H₂O) Calcd.(%): C, 56.97; H, 5.78; N, 2.89; S, 19.84 Found(%): C, 57.03; H, 5.67; N, 3.19; S, 19.73

[0630] 300MHz ¹H-NMR(CDCl₃) δ: 1.09–1.32(3H, m), 1.39–1.50(2H, m), 1.54–1.77(4H, m), 1.97–2.20(5H ,m), 2.35(2H, t, J=7.2Hz), 2.52 and 2.53(total 3H, each s), 2.54(1H, m), 3.79(1H, m), 5.31–5.45(2H, m), 6.43 and 6.47(total 1H, each d, J=7.5 and 6.6Hz), 6.76(1H, m), 7.39(1H, t-like), 7.40(1H, dd, J=2.1 and 3.6Hz), 7.52(1H, dd, J=2.1 and 4.2Hz).

[0631] IR(CHCl₃): 3510, 3443, 3425, 3092, 1708, 1650, 1531, 1503, 1437, 1237 cm⁻¹.

[0632] [α]_D²³+68.6±1.1° (c=1.011, MeOH)

[0633] Elemental Analysis (C₂₄H₂₉NO₄S₃•0.2H₂O) Calcd.(%): C, 58.20; H, 5.98; N, 2.83; S, 19.42 Found(%): C, 58.18; H, 5.67; N, 2.90; S, 19.11

[0634] 300MHz ¹H-NMR(CDCl₃) δ: 1.13(1H, m), 1.21–1.34(2H, m), 1.45–1.52(2H, m), 1.59–1.78(4H, m), 2.03–2.23(5H, m), 2.37(2H, t, J=7.2Hz), 2.58(1H, m), 3.86(1H, m), 5.32–5.46(2H, m), 6.28(1H, d, J=6.6Hz), 7.20(1H, dd, J=3.9 and 5.1Hz), 7.59(1H, d, J=3.9Hz), 7.75(1H, dd, J=1.2 and 5.1Hz), 7.81(1H, d, J=3.9Hz), 7.92(1H, dd, J=1.2 and 3.9Hz).

[0635] IR(CHCl₃): 3518, 3442, 3425, 3109, 1709, 1651, 1622, 1529, 1508, 1442, 1414, 1356, 1286, 1267 cm⁻¹.

[0636] [α]_D²³+89.2±1.3° (c=1.002, MeOH)

[0637] Elemental Analysis (C₂₄H₂₇NO₄S₂•0.2H₂O) Calcd.(%): C, 62.50; H, 5.99; N, 3.04; S, 13.90 Found(%): C, 62.63; H, 6.07; N, 2.97; S, 13.60

[0638] 300MHz ¹H-NMR(CDCl₃) δ: 1.12(1H, m), 1.22–1.33(2H, m), 1.44–1.52(2H, m), 1.59–1.79(4H, m), 2.03–2.24(5H, m), 2.37(2H, t, J=7.2Hz), 2.57(1H, m), 3.87(1H, m), 4.14(3H, s), 5.32–5.47(2H, m), 6.14(1H, d, J=7.5Hz), 7.08(1H, dd, J=3.9 and 5.4Hz), 7.27(1H, dd, J=1.2 and 3.9Hz), 7.39(1H, dd, J=1.2 and 5.4Hz), 7.41(1H, d, J=3.9Hz), 7.49(1H, d, J=3.9Hz).

[0639] IR(CHCl₃): 3516, 3444, 3425, 2665, 1709, 1649, 1529, 1498, 1049 cm⁻¹.

[0640] [α]_D²⁴+73.3±1.1° (c=1.003, MeOH)

[0641] Elemental Analysis (C₂₆H₃₀N₂O₄S₂•0.6H₂O) Calcd.(%): C, 60.36; H, 6.32; N, 5.63; S, 12.89 Found(%): C, 60.30; H, 6.14; N, 5.84; S, 12.95

[0642] 300MHz ¹H-NMR(CDCl₃) δ: 1.08(1H, m), 1.19–1.30(2H, m), 1.40–1.50(2H, m), 1.55–1.82(4H, m), 1.98–2.21(5H ,m), 2.36(2H, t, J=7.2Hz), 2.53(1H, m), 3.83(1H, m), 5.30–5.44(2H, m), 5.96(1H, d, J=7.5Hz), 6.43(1H, br), 6.52(1H, d, J=3.9Hz), 6.90(1H, m), 7.08–7.11(2H, m), 7.26–7.32(3H, m).

[0643] IR(CHCl₃): 3514, 3444, 3419, 1739, 1709, 1633, 1601, 1500, 1456 cm⁻¹.

[0644] [α]_D²²+86.6±1.3° (c=1.005, MeOH)

[0645] Elemental Analysis (C₂₅H₃₀N₂O₃S•0.1H₂O) Calcd.(%): C, 68.18; H, 6.91; N, 6.36; S, 7.28 Found(%): C, 68.11; H, 6.95; N, 6.43; S, 7.31

[0646] 300MHz ¹H-NMR(CDCl₃) δ: 1.05(1H, m), 1.18–1.30(2H, m), 1.39–1.48(2H, m), 1.54–1.83(4H, m), 1.98–2.21(5H ,m), 2.35(2H, t, J=7.2Hz), 2.51(1H, m), 3.38(3H, s), 3.80(1H, m), 5.29–5.42(2H, m), 5.82(1H, d, J=6.0Hz), 6.15(1H, d, J=4.2Hz), 7.11–7.39(6H, m).

[0647] IR(CHCl₃): 3514, 3446, 3425, 1741, 1709, 1628, 1597, 1477, 1415 cm⁻¹.

[0648] [α]_D²²+83.2±1.2° (c=1.001, MeOH)

[0649] Elemental Analysis (C₂₆H₃₂N₂O₃S) Calcd.(%): C, 69.00; H, 7.13; N, 6.19; S, 7.08 Found(%): C, 68.74; H, 7.08; N, 6.15; S, 7.01