Substituted amine derivatives and methods of use

FIELD OF THE INVENTION

BACKGROUND OF THE INVENTION

DESCRIPTION OF THE INVENTION

[0016]
wherein each of A¹ and A² is independently C, CH or N;

• [0017] wherein ring A is selected from
  • [0018] a) 5- or 6-membered partially saturated heterocyclyl,
    • [0019] preferably dihydropyran, dihydrothienyl, dihydrofuryl, oxo-dihydrofuryl, pyrrolinyl, dihydrothiazolyl, dihydro-oxazolyl, dihydro-isothiazolyl, dihydro-isoxazolyl, imidazolinyl and pyrazolinyl,
  • [0020] b) 5- or 6-membered heteroaryl,
    • [0021] preferably
      • [0022] I) 5-membered heteroaryl selected from thienyl, furanyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, pyrazolyl, isoxazolyl, triazolyl and isothiazolyl,
        • [0023] even more preferably 5-membered heteroaryl selected from

[0024]

• • • • • [0025]  specifically

[0026]

• • • • [0027] II) preferably 6-membered heteroaryl selected from pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, and triazinyl,
        • [0028] even more preferably 6-membered heteroaryl selected from

[0029]

• • • • • [0030]  more specifically

[0031]

• • [0032] c) 9-, 10- or 11-membered fused partially saturated heterocyclyl,
    • [0033] preferably tetrahydroquinolinyl,
  • [0034] d) 9- or 10-membered fused heteroaryl,
    • [0035] preferably
      • [0036] i) fused 9-membered fused heteroaryl selected from benzothienyl, benzothiazolyl, indolyl, benzimidazolyl, benzoxazolyl, benzofuryl, indazolyl and isoindolyl, and
      • [0037] ii) fused 10-membered heteroaryl selected from quinolyl, isoquinolyl, naphthpyridinyl, quinoxalinyl and quinazolinyl,
  • [0038] e) aryl, and
  • [0039] f) 4-, 5- or 6-membered cycloalkenyl,
    • [0040] preferably 5-membered cycloalkenyl,
      • [0041] more preferably cyclopentadienyl or cycloptenyl;
• [0042] wherein X is

[0043]

• • [0044] preferably X is selected from

[0045]

• • • [0046] more preferably X is

[0047]

• [0048] wherein Z is oxygen or sulfur;
• [0049] wherein R is selected from
  • [0050] a) substituted or unsubstituted 4-6 membered heterocyclyl,
    • [0051] preferably substituted or unsubstituted 5-6 membered heteroaryl comprising one or more nitrogen atoms,
      • [0052] more preferably pyrazolyl, triazolyl, pyridyl, pyrimidinyl, and pyridazinyl,
        • [0053] even more preferably 4-pyridyl, 3-pyridyl, 2-pyridyl, triazolyl, 4-pyrimidinyl and 4-pyridazinyl,
        • [0054]  most preferably 4-pyridyl,
  • [0055] b) substituted aryl,
    • [0056] preferably substituted phenyl,
      • [0057] more preferably optionally substituted (heterocyclyl-substituted phenyl), and
  • [0058] c) substituted or unsubstituted 9-14-membered bicyclic or tricyclic heterocyclyl,
    • [0059] preferably substituted or unsubstituted 9-10 membered bicyclic or 13-14 membered tricyclic heterocyclyl, more preferably substituted or unsubstituted 9-10 membered fused heterocyclyl,
      • [0060] even more preferably indazolyl, indolyl, isoindolyl, quinolinyl, isoquinolinyl, benzotriazolyl, 2,3-dihydrobenzofuryl, 1,2-dihydroquinolyl, naphthyridinyl and quinazolinyl,
        • [0061] even more preferably 5-indazolyl, 6-indazolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, indolyl, isoindolyl, benzotriazolyl, 2,3-dihydrobenzofuryl, 1,2-dihydroquinolyl, quinozalinyl, 4-isoquinolyl, 5-isoquinolyl, naphthyridinyl and 6-isoquinolyl,
        • [0062] especially preferred is 6-indazolyl;
    • [0063] wherein substituted R is substituted with one or more substituents independently selected from halo, —OR³, —SR³, —SO₂R³, —CO₂R³, —CONR³R³, —COR³, —NR³R³, —SO₂NR³R³, —NR³C(O)OR³, —NR³C(O)R³, —NR³C(O)NR³R³, cycloalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, nitro, oxo, alkylaminoalkoxyalkoxy, cyano, alkylaminoalkoxy, lower alkyl substituted with R², lower alkenyl substituted with R², and lower alkynyl substituted with R²;
      • [0064] preferably halo, —OR³, —SR³, —SO₂R³, —CO₂R³, —CONR³R³, —COR³, —NR³R³, —SO₂NRR³, —NR³C(O)OR³, —NR³C(O)R³, C_3-6-cycloalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, nitro, C_1-4-alkylamino-C_1-4-alkoxy-C_1-4-alkoxy, cyano, C_1-4-alkylamino-C_1-4-alkoxy, C_1-2-alkyl substituted with R², C_2-3-alkenyl substituted with R², and C_2-3-alkynyl substituted with R²,
        • [0065] more preferably halo, hydroxy, C_1-4-alkyl, C_1-2-alkoxy, optionally substituted 4-6 membered heterocyclyl-C_1-2-alkoxy, amino, C_1-2-alkylamino, aminosulfonyl, —NR³C(O)OR³, —NR³C(O)R³, C_3-6-cycloalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, nitro, C_1-2-alkylamino-C_1-2-alkoxy-C_1-2-alkoxy, cyano, C_1-2-alkylamino-C_1-2-alkoxy, C_1-2-alkylamino-C_1-2-alkyl, C_1-2-alkylamino-C_2-3-alkynyl, C_1-2-hydroxyalkyl, C_1-2-aminoalkyl, C_1-2-haloalkyl, optionally substituted 4-6 membered heterocyclyl-C_2-3-alkenyl, and optionally substituted 4-6 membered heterocyclyl-C_2-3-alkynyl,
        • [0066]  even more preferably chloro, fluoro, bromo, hydroxy, methoxy, ethoxy, amino, dimethylamino, diethylamino, 1-methylpiperidinylmethoxy, aminosulfonyl, cyclohexyl, dimethylaminopropynyl, dimethylaminoethoxy, 3-(4-morpholinyl)propyn-1-yl, dimethylaminoethoxyethoxy, optionally substituted piperidinyl, morpholinyl, optionally substituted piperazinyl, optionally substituted phenyl, methyl, ethyl, propyl, cyano, hydroxymethyl, aminomethyl, nitro and trifluoromethyl;
• [0067] wherein R¹ is selected from
  • [0068] a) substituted or unsubstituted 6-10 membered aryl,
    • [0069] preferably phenyl, naphthyl, indanyl, indenyl and tetrahydronaphthyl,
      • [0070] more preferably phenyl, tetrahydronaphthyl, and naphthyl,
  • [0071] b) substituted or unsubstituted 4-6 membered heterocyclyl,
    • [0072] preferably 5-6 membered heteroaryl,
      • [0073] more preferably isoxazolyl, pyrazolyl, thiazolyl, thiadiazolyl, thienyl, pyridyl, pyrimidinyl, pyridazinyl, imidazolyl, oxazolyl, furyl and pyrrolyl,
  • [0074] c) substituted or unsubstituted 9-14 membered bicyclic or tricyclic heterocyclyl,
    • [0075] preferably 9-10 membered bicyclic or 13-14 membered tricyclic heterocyclyl,
      • [0076] more preferably indazolyl, indolyl, isoindolyl, 2,3-dihydro-1H-indolyl, naphthyridinyl, 2,1,3-benzothiadiazolyl, isoquinolyl, quinolyl, 1,2-dihydroquinolyl, 1,2,3,4-tetrahydro-isoquinolyl, 2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluorenyl, 5,6,7-trihydro-1,2,4-triazolo[3,4-a]isoquinolyl, benzo[d]isothiazolyl, benzothienyl, tetrahydroquinolyl, benzofuryl, dihydrobenimidazolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, benzodioxanyl and quinazolinyl,
  • [0077] d) cycloalkyl,
    • [0078] preferably C_3-6-cycloalkyl,
      • [0079] more preferably cyclohexyl, and
  • [0080] e) cycloalkenyl,
    • [0081] wherein substituted R¹ is substituted with one or more substituents independently selected from halo, oxo, —OR³, —SR³, —CO₂R³, —CONR³R³, —COR³, —NR³R³, —NH(C₁-C₄ alkylenylR¹⁴), —SO₂R³, —SO₂NR³R³, —NR³C(O)OR³, —NR³C(O)R³, —NR³C(O)NR³R³, optionally substituted cycloalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, halosulfonyl, cyano, alkylaminoalkoxy, alkylaminoalkoxyalkoxy, nitro, lower alkyl substituted with R², lower alkenyl substituted with R², and lower alkynyl substituted with R²,
      • [0082] preferably halo, —OR³, oxo, —SR³, —SO₂R³, —CO₂R³, —CONR³R³, —COR³, —NR³R³, —NH(C₁-C₄ alkylenylR³), —(C₁-C₄ alkylenyl)NR³R³, —SO₂NR³R³, —NR³C(O)R³, —NR³C(O)R³, C₁-C₆-alkylamino-C₁-C₆-alkoxy, C₁-C₆-alkylamino-C₁-C₆-alkoxy-C₁-C₆-alkoxy, halosulfonyl, optionally substituted 4-6 membered heterocyclylcarbonylalkyl, C_1-4-alkoxycarbonylamino-C_1-6-alkyl,

[0083]

• • • • [0084]  optionally substituted C_3-6-cycloalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, optionally substituted phenyl-C_1-6-alkylenyl, optionally substituted 4-6 membered heterocyclyl-C₁-C₆-alkylenyl, 4-6 membered heterocyclyl-C₂-C₆-alkenylenyl, C_1-4-alkyl, cyano, C_1-4-hydroxyalkyl, nitro and C_1-4-haloalkyl,
      • [0085] more preferably halo, C_1-4-alkyl, optionally substituted C_3-6-cycloalkyl, optionally substituted phenyl, optionally substituted phenyl-C₁-C₄-alkylenyl, C_1-2-haloalkoxy, optionally substituted phenyloxy, optionally substituted 4-6 membered heterocyclyl-C₁-C₄-alkylenyl, optionally substituted 4-6 membered heterocyclyl-C₂-C₄-alkenylenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyloxy, optionally substituted 4-6 membered heterocyclylsulfonyl, optionally substituted 4-6 membered heterocyclylamino, optionally substituted 4-6 membered heterocyclylcarbonyl, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkylcarbonyl, C_1-2-haloalkyl, C_1-4-aminoalkyl, nitro, amino, hydroxy, oxo, cyano, aminosulfonyl, C_1-2-alkylsulfonyl, halosulfonyl, C_1-4-alkylcarbonyl, C_1-3-alkylamino-C_1-3-alkyl, C_1-3-alkylamino-C_1-3-alkoxy, C_1-3-alkylamino-C_1-3-alkoxy-C_1-3-alkoxy, C_1-4-alkoxycarbonyl, C_1-4-alkoxycarbonylamino-C_1-4-alkyl, C_1-4-hydroxyalkyl,

[0086]

• • • • [0087]  and C_1-4-alkoxy, and
      • [0088] even more preferably bromo, chloro, fluoro, iodo, nitro, amino, cyano, aminoethyl, Boc-aminoethyl, hydroxy, oxo, aminosulfonyl, 4-methylpiperazinylsulfonyl, cyclohexyl, phenyl, phenylmethyl, morpholinylmethyl, 1-methylpiperazin-4-ylmethyl, 1-methylpiperazin-4-ylpropyl, morpholinylpropyl, piperidin-1-ylmethyl, 1-methylpiperidin-4-ylmethyl, 2-methyl-2-(1-methylpiperidin-4-yl)ethyl, morpholinylethyl, 1-(4-morpholinyl)-2,2-dimethylpropyl, piperidin-4-ylethyl, 1-Boc-piperidin-4-ylethyl, piperidin-1-ylethyl, 1-Boc-piperidin-4-ylethyl, piperidin-4-ylmethyl, 1-Boc-piperidin-4-ylmethyl, piperidin-4-ylpropyl, 1-Boc-piperidin-4-ylpropyl, piperidin-1-ylpropyl, pyrrolidin-1-ylpropyl, pyrrolidin-2-ylpropyl, 1-Boc-pyrrolidin-2-ylpropyl, pyrrolidin-1-ylmethyl, pyrrolidin-2-ylmethyl, 1-Boc-pyrrolidin-2-ylmethyl, pyrrolidinylpropenyl, pyrrolidinylbutenyl, fluorosulfonyl, methylsulfonyl, methylcarbonyl, Boc, piperidin-1-ylmethylcarbonyl, 4-methylpiperazin-1-ylcarbonylethyl, methoxycarbonyl, aminomethylcarbonyl, dimethylaminomethylcarbonyl, 3-ethoxycarbonyl-2-methyl-fur-5-yl, 4-methylpiperazin-1-yl, 4-methyl-1-piperidyl, 1-Boc-4-piperidyl, piperidin-4-yl, 1-methylpiperidin-4-yl, 1-methyl-(1,2,3,6-tetrahydropyridyl), imidazolyl, morpholinyl, 4-trifluoromethyl-1-piperidinyl, hydroxybutyl, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, sec-butyl, trifluoromethyl, pentafluoroethyl, nonafluorobutyl, dimethylaminopropyl, 1,1-di(trifluoromethyl)-1-hydroxymethyl, 1,1-di(trifluoromethyl)-1-(piperidinylethoxy)methyl, 1,1-di(trifluoromethyl)-1-(methoxyethoxyethoxy)methyl, 1-hydroxyethyl, 2-hydroxyethyl, trifluoromethoxy, 1-aminoethyl, 2-aminoethyl, 1-(N-isopropylamino) ethyl, 2-(N-isopropylamino)ethyl, dimethylaminoethoxy, 4-chlorophenoxy, phenyloxy, azetidin-3-ylmethoxy, 1-Boc-azetidin-3-ylmethoxy, pyrrol-2-ylmethoxy, 1-Boc-pyrrol-2-ylmethoxy, pyrrol-1-ylmethoxy, 1-methyl-pyrrol-2-ylmethoxy, 1-isopropyl-pyrrol-2-ylmethoxy, 1-Boc-piperdin-4-ylmethoxy, piperdin-4-ylmethoxy, 1-methylpiperdin-4-yloxy, isopropoxy, methoxy and ethoxy;
• [0089] wherein R² is one or more substituents independently selected from H, halo, —OR³, oxo, —SR³, —CO₂R³, —COR³, —CONR³R³, —NR³R³, —SO₂NR³R³, —NR³C(O)OR³, —NR³C(O)R³, cycloalkyl, optionally substituted phenylalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted heteroarylalkyl, optionally substituted phenyl, lower alkyl, cyano, lower hydroxyalkyl, lower carboxyalkyl, nitro, lower alkenyl, lower alkynyl, C_1-4-alkoxy-C_1-4-alkoxy and C_1-4-alkoxy-C_1-4-alkoxy-C_1-4-alkoxy, lower aminoalkyl, lower alkylaminoalkyl and lower haloalkyl,
  • [0090] preferably H, halo, —OR³, —SR³, —CO₂R³, —CONR³R³, —COR³, —NR³R³, —SO₂NR³R³, —NR³C(O)OR³, —NR³C(O)R³, C_3-6-cycloalkyl optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, C_1-6-alkyl, cyano, C_1-4-hydroxyalkyl, C_1-4-carboxyalkyl, nitro, C_1-3-alkoxy-C_1-2-alkoxy, C_1-3-alkoxy-C_1-3-alkoxy-C_1-3-alkoxy, C_2-3-alkenyl, C_2-3-alkynyl and C_1-4-haloalkyl,
    • [0091] more preferably H, halo, hydroxy, C_1-2-alkoxy, C_1-2-haloalkoxy, amino, C_1-2-alkylamino, optionally substituted 4-6 membered heterocyclyl-C_1-2-alkylamino, aminosulfonyl, C_3-6-cycloalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, C_1-4-alkyl, cyano, C_1-2-hydroxyalkyl, C_1-3-carboxyalkyl, nitro, C_2-3-alkenyl, C_2-3-alkynyl and C_1-2-haloalkyl, and
      • [0092] even more preferably H, chloro, fluoro, bromo, hydroxy, methoxy, ethoxy, trifluoromethoxy, amino, dimethylamino, aminosulfonyl, carboxymethyl, cyclopropyl, optionally substituted phenyl, methyl, ethyl, propyl, cyano, hydroxymethyl, nitro, propenyl, propynyl and trifluoromethyl and unsubstituted or substituted heteroaryl selected
        • [0093] from thienyl, furanyl, pyridyl, imidazolyl, and pyrazolyl;
• [0094] wherein R³ is selected from H, lower alkyl, optionally substituted phenyl, optionally substituted 3-6 membered heterocyclyl, optionally substituted C₃-C₆-cycloalkyl, optionally substituted phenylalkyl, optionally substituted 3-6 membered heterocyclylalkyl, optionally substituted C₃-C₆ cycloalkylalkyl, and lower haloalkyl,
  • [0095] preferably H, C_1-4-alkyl, optionally substituted phenyl, optionally substituted phenyl-C_1-4-alkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkyl, optionally substituted C₃-C₆ cycloalkyl and C_1-2-haloalkyl,
    • [0096] more preferably H, methyl, phenyl, cyclopropyl, cyclohexyl, benzyl, morpholinylmethyl, 4-methylpiperazinylmethyl, azetidinyl, azetidinylmethyl, 4-methylpiperdinylmethyl, 4-morpholinylmethyl, 4-morpholinylethyl, 1-(4-morpholinyl)-2,2-dimethylpropyl, 1-piperdinylethyl, 1-piperdinylpropyl, 1-pyrrolidinylpropyl and trifluoromethyl;
• [0097] wherein R⁴ is independently selected from a direct bond, C_2-4-alkylenyl, C_2-4-alkenylenyl and C_2-4-alkynylenyl, where one of the CH₂ groups may be replaced with an oxygen atom or an —NH—, wherein R⁴ is optionally substituted with hydroxy,
  • [0098] preferably a direct bond or R^4a;
• [0099] wherein R^4a is selected from C_2-4-alkylenyl where one of the CH₂ groups may be replaced with an oxygen atom or an —NH—, wherein R^4a is optionally substituted with hydroxy;
  • [0100] preferably ethyl, butyl, and

[0101]

• [0102] wherein R⁵ is selected from H, lower alkyl, optionally substituted phenyl and optionally substituted lower aralkyl,
  • [0103] preferably H, methyl or ethyl,
    • [0104] more preferably H;
• [0105] wherein R^5a is selected from H, lower alkyl, optionally substituted phenyl and lower aralkyl,
  • [0106] preferably H, methyl or ethyl,
    • [0107] more preferably H;
• [0108] wherein R⁷ is selected from H, C_1-6-alkyl, optionally substituted phenyl, optionally substituted phenyl-C_1-6-alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyl-alkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyl-C₁-C₆-alkyl, C_1-4-alkoxy-C_1-4-alkyl and C_1-4-alkoxy-C_1-4-alkoxy-C_1-4-alkyl,
  • [0109] preferably H, C_1-3-alkyl, optionally substituted phenyl, optionally substituted phenyl-C_1-3-alkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyl-C₁-C₃-alkyl, C_1-3-alkoxy-C_1-2-alkyl and C_1-3-alkoxy-C_1-3-alkoxy-C_1-3-alkyl;
• [0110] wherein R^c is selected from H, methyl and optionally substituted phenyl; and
• [0111] wherein R^e and R^f are independently selected from H and C_1-2-haloalkyl, preferably —CF₃;
• [0112] wherein R¹⁴ is selected from H, optionally substituted phenyl, optionally substituted 4-6 membered heterocyclyl and optionally substituted C₃-C₆ cycloalkyl;
• [0113] provided A is not pyridyl when X is —C(O)NH— and when R¹ is 4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl when R⁵ is methyl and when R is 4-methylpiperidyl;
• [0114] further provided A is not pyridyl when X is —C(O)NH—, when R⁵ is H, when R² is 6-methyl and when R is indazolyl;
• [0115] further provided A is not phenyl when X is —C(O)NH—, when R¹ is phenyl, 4-bromophenyl, 2-methylphenyl, 4-methoxyphenyl, when R⁵ is H and when R is 4-pyridyl; further provided A is not phenyl when X is —C(O)NH—, when R¹ is phenyl, when R⁵ is H and when R is 2-oxobenzopyan-4-yl;
• [0116] further provided A is not phenyl when X is —C(O)NH—, when R¹ is phenyl, 4-chlorophenyl, 3-nitrophenyl, 4-methoxyphenyl, when R⁵ is H and when R is 4-imidazolinyl;
• [0117] further provided A is not phenyl when X is —C(O)NH—, when R⁵ is H, when R⁵ is substituted benzyl and when R is substituted triazinyl;
• [0118] further provided A is not phenyl when X is —C(O)NH—, when R¹ is phenyl or 2-chlorophenyl, when R⁵ is H and when R is 4-quinazolinyl;
• [0119] further provided A is not phenyl when X is —C(O)NH—, when R¹ is phenyl, when R⁵ is H and when R is isoquinolin-1-yl;
• [0120] further provided A is not phenyl when X is —C(O)NH—, when R¹ is 2-chlorophenyl or 4-chlorophenyl, when R⁵ is H and when R is 3-chloroisoquinolin-1-yl;
• [0121] further provided A is not phenyl when X is —C(O)NH—, when R¹ is 1-ethylpiperid-3-yl or 1-ethylpiperid-4-yl, when R⁵ is H and when R is 8-trifluoromethylquinolin-4-yl;
• [0122] further provided A is not phenyl when X is —C(O)NH—, when R¹ is 1-ethylpiperid-3-yl, when R⁵ is H and when R is 8-chloroquinolin-4-yl;
• [0123] further provided A is not phenyl when X is —C(O)NH—, when R¹ is halo substituted phenyl, 1-butylpiperid-4-yl, 1-ethylpiperid-3-yl or 1-ethylpiperid-4-yl, when R⁵ is H and when R is 7-chloroquinolin-4-yl; and
• [0124] further provided R is not unsubstituted 2-thienyl, unsubstituted 2-pyridyl or unsubstituted 3-pyridyl.

[0126]
wherein R is selected from unsubstituted or substituted 9- or 10-membered fused nitrogen-containing heteroaryl,

• • [0127] preferably indolyl, isoindolyl, indazolyl, quinolyl, isoquinolyl, naphthyridinyl and quinozalinyl,
  • [0128] more preferably 6-indazolyl,
  • [0129]  where R is substituted with one or more substituents selected from halo, amino, hydroxy, C_1-6-alkyl, C_1-6-haloalkyl, C_1-6-alkoxy, C_1-6-alkylamino-C_2-4-alkynyl, C_1-6-alkylamino-C_1-6-alkoxy, C_1-6-alkylamino-C_1-6-alkoxy-C_1-6-alkoxy, optionally substituted heterocyclyl-C_2-4-alkynyl, and optionally substituted heterocyclylalkoxy,
  • [0130] preferably chloro, fluoro, amino, hydroxy, methyl, ethyl, propyl, trifluoromethyl, dimethylaminopropynyl, 1-methylpiperdinylmethoxy, dimethylaminoethoxyethoxy, methoxy and ethoxy;
• [0131] wherein R¹ is selected from unsubstituted or substituted aryl,
  • [0132] preferably phenyl, tetrahydronaphthyl, indanyl, indenyl and naphthyl,
  • [0133] cycloalkyl,
  • [0134] preferably cyclohexyl,
  • [0135] 4-6 membered heterocyclyl,
  • [0136] preferably isoxazolyl, pyrazolyl, thiazolyl, thiadiazolyl, thienyl, pyridyl, pyrimidinyl and pyridazinyl, and
  • [0137] 9-10 membered bicyclic and 13-14 membered tricyclic heterocyclyl,
  • [0138] preferably 1,2-dihydroquinolyl, 1,2,3,4-tetrahydro-isoquinolyl, isoquinolyl, quinolyl, indolyl, isoindolyl, 2,3-dihydro-1H-indolyl, naphthyridinyl, quinozalinyl, benzo[d]isothiazolyl, 2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluorenyl, 5,6,7-trihydro-1,2,4-triazolo[3,4-a]isoquinolyl, tetrahydroquinolinyl, indazolyl, 2,1,3-benzothiadiazolyl, benzodioxanyl, benzothienyl, benzofuryl, benzimidazolyl, benzoxazolyl and benzthiazolyl;
  • [0139]  wherein substituted R¹ is substituted with one or more substituents selected from halo, C_1-4-alkyl, optionally substituted C_3-6-cycloalkyl, optionally substituted phenyl, optionally substituted phenyl-C₁-C₄-alkylenyl, C_1-2-haloalkoxy, optionally substituted phenyloxy, optionally substituted 4-6 membered heterocyclyl-C₁-C₄-alkylenyl, optionally substituted 4-6 membered heterocyclyl-C₂-C₄-alkenylenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyloxy, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkoxy, optionally substituted 4-6 membered heterocyclylsulfonyl, optionally substituted 4-6 membered heterocyclylamino, optionally substituted 4-6 membered heterocyclylcarbonyl, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkylcarbonyl, C_1-2-haloalkyl, C_1-4-aminoalkyl, nitro, amino, hydroxy, cyano, aminosulfonyl, C_1-2-alkylsulfonyl, halosulfonyl, C_1-4-alkylcarbonyl, C_1-3-alkylamino-C_1-3-alkyl, C_1-3-alkylamino-C_1-3-alkoxy, C_1-3-alkylamino-C_1-3-alkoxy-C_1-3-alkoxy, C_1-4-alkoxycarbonyl, C_1-4-alkoxycarbonylamino-C_1-4alkyl, C₁₄-hydroxyalkyl,

[0140]

• • [0141]  and C_1-4-alkoxy,
  • [0142] preferably bromo, chloro, fluoro, iodo, nitro, amino, cyano, aminoethyl, Boc-aminoethyl, hydroxy, oxo, aminosulfonyl, 4-methylpiperazinylsulfonyl, cyclohexyl, phenyl, phenylmethyl, morpholinylmethyl, 1-methylpiperazin-4-ylmethyl, 1-methylpiperazin-4-ylpropyl, morpholinylpropyl, piperidin-1-ylmethyl, 1-methylpiperidin-4-ylmethyl, 2-methyl-2-(1-methylpiperidin-4-yl)ethyl, morpholinylethyl, 1-(4-morpholinyl)-2,2-dimethylpropyl, piperidin-4-ylethyl, 1-Boc-piperidin-4-ylethyl, piperidin-1-ylethyl, 1-Boc-piperidin-4-ylethyl, piperidin-4-ylmethyl, 1-Boc-piperidin-4-ylmethyl, piperidin-4-ylpropyl, 1-Boc-piperidin-4-ylpropyl, piperidin-1-ylpropyl, pyrrolidin-1-ylpropyl, pyrrolidin-2-ylpropyl, 1-Boc-pyrrolidin-2-ylpropyl, pyrrolidin-1-ylmethyl, pyrrolidin-2-ylmethyl, 1-Boc-pyrrolidin-2-ylmethyl, pyrrolidinylpropenyl, pyrrolidinylbutenyl, fluorosulfonyl, methylsulfonyl, methylcarbonyl, Boc, piperidin-1-ylmethylcarbonyl, 4-methylpiperazin-1-ylcarbonylethyl, methoxycarbonyl, aminomethylcarbonyl, dimethylaminomethylcarbonyl, 3-ethoxycarbonyl-2-methyl-fur-5-yl, 4-methylpiperazin-1-yl, 4-methyl-1-piperidyl, 1-Boc-4-piperidyl, piperidin-4-yl, 1-methylpiperidin-4-yl, 1-methyl-(1,2,3,6-tetrahydropyridyl), imidazolyl, morpholinyl, 4-trifluoromethyl-1-piperidinyl, hydroxybutyl, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, sec-butyl, trifluoromethyl, pentafluoroethyl, nonafluorobutyl, dimethylaminopropyl, 1,1-di(trifluoromethyl)-1-hydroxymethyl, 1,1-di(trifluoromethyl)-1-(piperidinylethoxy)methyl, 1,1-di(trifluoromethyl)-1-(methoxyethoxyethoxy)methyl, 1-hydroxyethyl, 2-hydroxyethyl, trifluoromethoxy, 1-aminoethyl, 2-aminoethyl, 1-(N-isopropylamino)ethyl, 2-(N-isopropylamino)ethyl, dimethylaminoethoxy, 4-chlorophenoxy, phenyloxy, azetidin-3-ylmethoxy, 1-Boc-azetidin-3-ylmethoxy, pyrrol-2-ylmethoxy, 1-Boc-pyrrol-2-ylmethoxy, pyrrol-1-ylmethoxy, 1-methyl-pyrrol-2-ylmethoxy, 1-isopropyl-pyrrol-2-ylmethoxy, 1-Boc-piperdin-4-ylmethoxy, piperdin-4-ylmethoxy, 1-methylpiperdin-4-yloxy, isopropoxy, methoxy and ethoxy;
• [0143] wherein R² is one or more substituents independently selected from
  • [0144] H,
  • [0145] halo,
  • [0146] hydroxy,
  • [0147] amino,
  • [0148] C_1-6-alkyl,
  • [0149] C_1-6-haloalkyl,
  • [0150] C_1-6-alkoxy,
  • [0151] C_1-2-alkylamino,
  • [0152] aminosulfonyl,
  • [0153] C_3-6-cycloalkyl,
  • [0154] cyano,
  • [0155] C_1-2-hydroxyalkyl,
  • [0156] nitro,
  • [0157] C_2-3-alkenyl,
  • [0158] C_2-3-alkynyl,
  • [0159] C_1-6-haloalkoxy,
  • [0160] C_1-6-carboxyalkyl,
  • [0161] 5-6-membered heterocyclyl-C_1-6-alkylamino,
  • [0162] unsubstituted or substituted phenyl and
  • [0163] unsubstituted or substituted 4-6 membered heterocyclyl;
  • [0164]  preferably H, chloro, fluoro, bromo, amino, hydroxy, methyl, ethyl, propyl, oxo, dimethylamino, aminosulfonyl, cyclopropyl, cyano, hydroxymethyl, nitro, propenyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, carboxymethyl, morpholinylethylamino, propynyl, unsubstituted or substituted phenyl and unsubstituted or substituted heteroaryl selected from thienyl, furanyl, pyridyl, imidazolyl, and pyrazolyl;
• [0165] wherein R⁴ is selected from a direct bond, C_1-4-alkyl, and

[0166]

• • [0167] preferably direct bond, ethyl, butyl, and

[0168]

• [0169] wherein R^e and R^f are independently selected from H and C_1-2-haloalkyl,
  • [0170] preferably —CF₃; and
• [0171] wherein R⁷ is selected from H, C_1-3-alkyl, optionally substituted phenyl, optionally substituted phenyl-C_1-3-alkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyl-C₁-C₃-alkyl, C_1-3-alkoxy-C_1-2-alkyl and C_1-3-alkoxy-C_1-3-alkoxy-C_1-3-alkyl.

[0173]
wherein R is selected from

• • [0174] unsubstituted or substituted 9- or 10-membered fused nitrogen-containing heteroaryl,
    • [0175] preferably indolyl, isoindolyl, indazolyl, quinolyl, isoquinolyl, naphthyridinyl and quinozalinyl,
    • [0176] more preferably 5-indazolyl and 6-indazolyl, even more preferably 6-indazolyl,
    • [0177]  where R is substituted with one or more substituents selected from halo, amino, hydroxy, C_1-6-alkyl, C_1-6-haloalkyl, C_1-6-alkoxy, C_1-6-alkylamino-C_2-4-alkynyl, C_1-6-alkylamino-C_1-6-alkoxy, C_1-6-alkylamino-C_1-6-alkoxy-C_1-6-alkoxy, optionally substituted heterocyclyl-C_2-4-alkynyl, and optionally substituted heterocyclylalkoxy,
    • [0178] preferably chloro, fluoro, amino, hydroxy, methyl, ethyl, propyl, trifluoromethyl, dimethylaminopropynyl, 1-methylpiperdinylmethoxy, dimethylaminoethoxyethoxy, methoxy and ethoxy;
• [0179] wherein R¹ is selected from unsubstituted or substituted aryl,
  • [0180] preferably phenyl, tetrahydronaphthyl, indanyl, indenyl and naphthyl,
  • [0181] cycloalkyl,
  • [0182] preferably cyclohexyl,

[0188]

• • [0189]  and C_1-4-alkoxy,
  • [0190] preferably bromo, chloro, fluoro, iodo, nitro, amino, cyano, aminoethyl, Boc-aminoethyl, hydroxy, aminosulfonyl, 4-methylpiperazinylsulfonyl, cyclohexyl, phenyl, phenylmethyl, morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinylpropyl, morpholinylpropyl, methylpiperidinylmethyl, morpholinylethyl, 1-(4-morpholinyl)-2,2-dimethylpropyl, piperidinylethyl, piperidinylmethyl, piperidinylpropyl, pyrrolidinylpropyl, pyrrolidinylpropenyl, pyrrolidinylbutenyl, fluorosulfonyl, methylsulfonyl, methylcarbonyl, piperidinylmethylcarbonyl, methylpiperazinylcarbonylethyl, methoxycarbonyl, 3-ethoxycarbonyl-2-methyl-fur-5-yl, methylpiperazinyl, methylpiperidyl, 1-methyl-(1,2,3,6-tetrahydropyridyl), imidazolyl, morpholinyl, 4-trifluoromethyl-1-piperidinyl, hydroxybutyl, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, sec-butyl, trifluoromethyl, pentafluoroethyl, nonafluorobutyl, dimethylaminopropyl, 1,1-di(trifluoromethyl)-1-hydroxymethyl, 1,1-di(trifluoromethyl)-1-(piperidinylethoxy)methyl, 1,1-di(trifluoromethyl)-1-(methoxyethoxyethoxy)methyl, 1-hydroxyethyl, 2-hydroxyethyl, trifluoromethoxy, 1-aminoethyl, 2-aminoethyl, 1-(N-isopropylamino)ethyl, 2-(N-isopropylamino)ethyl, dimethylaminoethoxy, 4-chlorophenoxy, phenyloxy, 1-methylpiperdin-4-yloxy, isopropoxy, methoxy and ethoxy;
• [0191] wherein R² is one or more substituents independently selected from
  • [0192] H,
  • [0193] halo,
  • [0194] hydroxy,
  • [0195] amino,
  • [0196] C_1-6-alkyl,
  • [0197] C_1-6-haloalkyl,
  • [0198] C_1-6-alkoxy,
  • [0199] C_1-2-alkylamino,
  • [0200] aminosulfonyl,
  • [0201] C_3-6-cycloalkyl,
  • [0202] cyano,
  • [0203] C_1-2-hydroxyalkyl,
  • [0204] nitro,
  • [0205] C_2-3-alkenyl,
  • [0206] C_2-3-alkynyl,
  • [0207] C_1-6-haloalkoxy,
  • [0208] C_1-6-carboxyalkyl,
  • [0209] 5-6-membered heterocyclyl-C_1-6-alkylamino,
  • [0210] unsubstituted or substituted phenyl and
  • [0211] unsubstituted or substituted 4-6 membered heterocyclyl;
  • [0212]  preferably H, chloro, fluoro, bromo, amino, hydroxy, methyl, ethyl, propyl, oxo, dimethylamino, aminosulfonyl, cyclopropyl, cyano, hydroxymethyl, nitro, propenyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, carboxymethyl, morpholinylethylamino, propynyl, unsubstituted or substituted phenyl and unsubstituted or substituted heteroaryl selected from thienyl, furanyl, pyridyl, imidazolyl, and pyrazolyl;
• [0213] wherein R⁴ is selected from a direct bond, C_1-4-alkyl, and

[0214]

• • [0215] preferably direct bond, ethyl, butyl, and

[0216]

• [0217] wherein R^e and R^f are independently selected from H and C_1-2-haloalkyl,
  • [0218] preferably —CF₃; and
• [0219] wherein R⁷ is selected from H, C_1-3-alkyl, optionally substituted phenyl-C_1-3-alkyl, 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyl-C₁-C₃-alkyl, C_1-3-alkoxy-C_1-2-alkyl and C_1-3-alkoxy-C_1-3-alkoxy-C_1-3-alkyl.

[0221]
wherein A³ is selected from CR² and N;

• [0222] wherein A⁴ is selected from CR² and N; provided one of A³ and A⁴ is not CR²;
• [0223] wherein R is selected from
  • [0224] unsubstituted or substituted 9- or 10-membered fused nitrogen-containing heteroaryl,
  • [0225] preferably indolyl, isoindolyl, indazolyl, quinolyl, isoquinolyl, naphthyridinyl and quinozalinyl,
  • [0226] more preferably 5-indazolyl and 6-indazolyl, even more preferably 6-indazolyl,
  • [0227]  where R is substituted with one or more substituents selected from halo, amino, hydroxy, C_1-6-alkyl, C_1-6-haloalkyl, C_1-6-alkoxy, C_1-6-alkylamino-C_2-4-alkynyl, C_1-6-alkylamino-C_1-6-alkoxy, C_1-6-alkylamino-C_1-6-alkoxy-C_1-6-alkoxy, optionally substituted heterocyclyl-C_2-4-alkynyl, and optionally substituted heterocyclylalkoxy,
  • [0228] preferably chloro, fluoro, amino, hydroxy, methyl, ethyl, propyl, trifluoromethyl, dimethylaminopropynyl, 1-methylpiperdinylmethoxy, dimethylaminoethoxyethoxy, methoxy and ethoxy;
• [0229] wherein R¹ is selected from unsubstituted or substituted aryl,
  • [0230] preferably phenyl, tetrahydronaphthyl, indanyl, indenyl and naphthyl,
  • [0231] cycloalkyl,
  • [0232] preferably cyclohexyl,
  • [0233] 4-6 membered heterocyclyl,
  • [0234] preferably isoxazolyl, pyrazolyl, thiazolyl, thiadiazolyl, thienyl, pyridyl, pyrimidinyl and pyridazinyl, and
  • [0235] 9-10 membered bicyclic and 13-14 membered tricyclic heterocyclyl,
  • [0236] preferably 1,2-dihydroquinolyl, 1,2,3,4-tetrahydro-isoquinolyl, isoquinolyl, quinolyl, indolyl, isoindolyl, 2,3-dihydro-1H-indolyl, naphthyridinyl, quinozalinyl, 2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluorenyl, 5,6,7-trihydro-1,2,4-triazolo[3,4-a]isoquinolyl, tetrahydroquinolinyl, indazolyl, benzo[d]isothiazolyl, 2,1,3-benzothiadiazolyl, benzodioxanyl, benzothienyl, benzofuryl, benzimidazolyl, benzoxazolyl and benzthiazolyl;
  • [0237]  wherein R¹ is substituted with one or more substituents selected from halo, C_1-4-alkyl, optionally substituted C_3-6-cycloalkyl, optionally substituted phenyl, optionally substituted phenyl-C₁-C₄-alkylenyl, C_1-2-haloalkoxy, optionally substituted phenyloxy, optionally substituted 4-6 membered heterocyclyl-C₁-C₄-alkylenyl, optionally substituted 4-6 membered heterocyclyl-C₂-C₄-alkenylenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyloxy, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkoxy, optionally substituted 4-6 membered heterocyclylsulfonyl, optionally substituted 4-6 membered heterocyclylamino, optionally substituted 4-6 membered heterocyclylcarbonyl, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkylcarbonyl, C_1-2-haloalkyl, C_1-4-aminoalkyl, nitro, amino, hydroxy, cyano, aminosulfonyl, C_1-2-alkylsulfonyl, halosulfonyl, C_1-4-alkylcarbonyl, C_1-3-alkylamino-C_1-3-alkyl, C_1-3-alkylamino-C_1-3-alkoxy, C_1-3-alkylamino-C_1-3-alkoxy-C_1-3-alkoxy, C_1-4-alkoxycarbonyl, C_1-4-alkoxycarbonylamino-C_1-4-alkyl, C₁₄-hydroxyalkyl,

[0238]

• • [0239]  and C_1-4-alkoxy,
  • [0240] preferably bromo, chloro, fluoro, iodo, nitro, amino, cyano, aminoethyl, Boc-aminoethyl, hydroxy, aminosulfonyl, 4-methylpiperazinylsulfonyl, cyclohexyl, phenyl, phenylmethyl, morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinylpropyl, morpholinylpropyl, methylpiperidinylmethyl, morpholinylethyl, 1-(4-morpholinyl)-2,2-dimethylpropyl, piperidinylethyl, piperidinylmethyl, piperidinylpropyl, pyrrolidinylpropyl, pyrrolidinylpropenyl, pyrrolidinylbutenyl, fluorosulfonyl, methylsulfonyl, methylcarbonyl, piperidinylmethylcarbonyl, methylpiperazinylcarbonylethyl, methoxycarbonyl, 3-ethoxycarbonyl-2-methyl-fur-5-yl, methylpiperazinyl, methylpiperidyl, 1-methyl-(1,2,3,6-tetrahydropyridyl), imidazolyl, morpholinyl, 4-trifluoromethyl-1-piperidinyl, hydroxybutyl, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, sec-butyl, trifluoromethyl, pentafluoroethyl, nonafluorobutyl, dimethylaminopropyl, 1,1-di(trifluoromethyl)-1-hydroxymethyl, 1,1-di(trifluoromethyl)-1-(piperidinylethoxy)methyl, 1,1-di(trifluoromethyl)-1-(methoxyethoxyethoxy)methyl, 1-hydroxyethyl, 2-hydroxyethyl, trifluoromethoxy, 1-aminoethyl, 2-aminoethyl, 1-(N-isopropylamino)ethyl, 2-(N-isopropylamino)ethyl, dimethylaminoethoxy, 4-chlorophenoxy, phenyloxy, 1-methylpiperdin-4-yloxy, isopropoxy, methoxy and ethoxy;
• [0241] wherein R² is one or more substituents independently selected from
  • [0242] H,
  • [0243] halo,
  • [0244] hydroxy,
  • [0245] amino,
  • [0246] C_1-6-alkyl,
  • [0247] C_1-6-haloalkyl,
  • [0248] C_1-6-alkoxy,
  • [0249] C_1-2-alkylamino,
  • [0250] aminosulfonyl,
  • [0251] C_3-6-cycloalkyl,
  • [0252] cyano,
  • [0253] C_1-2-hydroxyalkyl,
  • [0254] nitro,
  • [0255] C_2-3-alkenyl,
  • [0256] C_2-3-alkynyl,
  • [0257] C_1-6-haloalkoxy,
  • [0258] C_1-6-carboxyalkyl,
  • [0259] 5-6-membered heterocyclyl-C_1-6-alkylamino,
  • [0260] unsubstituted or substituted phenyl and
  • [0261] unsubstituted or substituted 4-6 membered heterocyclyl;
  • [0262] preferably H, chloro, fluoro, bromo, amino, hydroxy, methyl, ethyl, propyl, oxo, dimethylamino, aminosulfonyl, cyclopropyl, cyano, hydroxymethyl, nitro, propenyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, carboxymethyl, morpholinylethylamino, propynyl, unsubstituted or substituted phenyl and unsubstituted or substituted heteroaryl selected from thienyl, furanyl, pyridyl, imidazolyl, and pyrazolyl;
• [0263] wherein R⁴ is selected from a direct bond, C_1-4-alkyl, and

[0264]

• • [0265] preferably direct bond, ethyl, butyl, and

[0266]

• [0267] wherein R^e and R^f are independently selected from H and C_1-2-haloalkyl,
  • [0268] preferably —CF₃; and
• [0269] wherein R⁷ is selected from H, C_1-3-alkyl, optionally substituted phenyl-C_1-3-alkyl, 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyl-C₁-C₃-alkyl, C_1-3-alkoxy-C_1-2-alkyl and C_1-3-alkoxy-C_1-3-alkoxy-C_1-3-alkyl.

[0271]

• [0272] wherein A⁵ is selected from S, O and NR⁶
• [0273] wherein R is selected from
  • [0274] unsubstituted or substituted 9- or 10-membered fused nitrogen-containing heteroaryl,
  • [0275] preferably indolyl, isoindolyl, indazolyl, quinolyl, isoquinolyl, naphthyridinyl and quinozalinyl,
  • [0276] more preferably 5-indazolyl and 6-indazolyl, even more preferably 6-indazolyl,
  • [0277]  where R is substituted with one or more substituents selected from halo, amino, hydroxy, C_1-6-alkyl, C_1-6-haloalkyl, C_1-6-alkoxy, C_1-6-alkylamino-C_2-4-alkynyl, C_1-6-alkylamino-C_1-6-alkoxy, C_1-6-alkylamino-C_1-6-alkoxy-C_1-6-alkoxy, optionally substituted heterocyclyl-C_2-4-alkynyl, and optionally substituted heterocyclylalkoxy,
  • [0278] preferably chloro, fluoro, amino, hydroxy, methyl, ethyl, propyl, trifluoromethyl, dimethylaminopropynyl, 1-methylpiperdinylmethoxy, dimethylaminoethoxyethoxy, methoxy and ethoxy;
• [0279] wherein R¹ is selected from unsubstituted or substituted aryl,
  • [0280] preferably phenyl, tetrahydronaphthyl, indanyl, indenyl and naphthyl,
  • [0281] cycloalkyl,
  • [0282] preferably cyclohexyl,
  • [0283] 4-6 membered heterocyclyl,
  • [0284] preferably isoxazolyl, pyrazolyl, thiazolyl, thiadiazolyl, thienyl, pyridyl, pyrimidinyl and pyridazinyl, and
  • [0285] 9-10 membered bicyclic and 13-14 membered tricyclic heterocyclyl,
  • [0286] preferably 1,2-dihydroquinolyl, 1,2,3,4-tetrahydro-isoquinolyl, isoquinolyl, quinolyl, indolyl, isoindolyl, 2,3-dihydro-1H-indolyl, naphthyridinyl, quinozalinyl, 2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluorenyl, 5,6,7-trihydro-1,2,4-triazolo[3,4-a]isoquinolyl, benzo[d]isothiazolyl, tetrahydroquinolinyl, indazolyl, 2,1,3-benzothiadiazolyl, benzodioxanyl, benzothienyl, benzofuryl, benzimidazolyl, benzoxazolyl and benzthiazolyl;
  • [0287]  wherein R¹ is substituted with one or more substituents selected from halo, C_1-4-alkyl, optionally substituted C_3-6-cycloalkyl, optionally substituted phenyl, optionally substituted phenyl-C₁-C₄-alkylenyl, C_1-2-haloalkoxy, optionally substituted phenyloxy, optionally substituted 4-6 membered heterocyclyl-C₁-C₄-alkylenyl, optionally substituted 4-6 membered heterocyclyl-C₂-C₄-alkenylenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyloxy, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkoxy, optionally substituted 4-6 membered heterocyclylsulfonyl, optionally substituted 4-6 membered heterocyclylamino, optionally substituted 4-6 membered heterocyclylcarbonyl, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkylcarbonyl, C_1-2-haloalkyl, C_1-4-aminoalkyl, nitro, amino, hydroxy, cyano, aminosulfonyl, C_1-2-alkylsulfonyl, halosulfonyl, C_1-4-alkylcarbonyl, C_1-3-alkylamino-C_1-3-alkyl, C_1-3-alkylamino-C_1-3-alkoxy, C_1-3-alkylamino-C_1-3-alkoxy-C_1-3-alkoxy, C_1-4-alkoxycarbonyl, C_1-4-alkoxycarbonylamino-C_1-4-alkyl, C_1-4-hydroxyalkyl,

[0288]

• • [0289]  and C_1-4-alkoxy,
  • [0290] preferably bromo, chloro, fluoro, iodo, nitro, amino, cyano, aminoethyl, Boc-aminoethyl, hydroxy, aminosulfonyl, 4-methylpiperazinylsulfonyl, cyclohexyl, phenyl, phenylmethyl, morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinylpropyl, morpholinylpropyl, methylpiperidinylmethyl, morpholinylethyl, 1-(4-morpholinyl)-2,2-dimethylpropyl, piperidinylethyl, piperidinylmethyl, piperidinylpropyl, pyrrolidinylpropyl, pyrrolidinylpropenyl, pyrrolidinylbutenyl, fluorosulfonyl, methylsulfonyl, methylcarbonyl, piperidinylmethylcarbonyl, methylpiperazinylcarbonylethyl, methoxycarbonyl, 3-ethoxycarbonyl-2-methyl-fur-5-yl, methylpiperazinyl, methylpiperidyl, 1-methyl-(1,2,3,6-tetrahydropyridyl), imidazolyl, morpholinyl, 4-trifluoromethyl-1-piperidinyl, hydroxybutyl, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, sec-butyl, trifluoromethyl, pentafluoroethyl, nonafluorobutyl, dimethylaminopropyl, 1,1-di(trifluoromethyl)-1-hydroxymethyl, 1,1-di(trifluoromethyl)-1-(piperidinylethoxy)methyl, 1,1-di(trifluoromethyl)-1-(methoxyethoxyethoxy)methyl, 1-hydroxyethyl, 2-hydroxyethyl, trifluoromethoxy, 1-aminoethyl, 2-aminoethyl, 1-(N-isopropylamino)ethyl, 2-(N-isopropylamino)ethyl, dimethylaminoethoxy, 4-chlorophenoxy, phenyloxy, 1-methylpiperdin-4-yloxy, isopropoxy, methoxy and ethoxy;
• [0291] wherein R² is one or more substituents independently selected from
  • [0292] H,
  • [0293] halo,
  • [0294] hydroxy,
  • [0295] amino,
  • [0296] C_1-6-alkyl,
  • [0297] C_1-6-haloalkyl,
  • [0298] C_1-6-alkoxy,
  • [0299] C_1-2-alkylamino,
  • [0300] aminosulfonyl,
  • [0301] C_3-6-cycloalkyl,
  • [0302] cyano,
  • [0303] C_1-2-hydroxyalkyl,
  • [0304] nitro,
  • [0305] C_2-3-alkenyl,
  • [0306] C_2-3-alkynyl,
  • [0307] C_1-6-haloalkoxy,
  • [0308] C_1-6-carboxyalkyl,
  • [0309] 5-6-membered heterocyclyl-C_1-6-alkylamino,
  • [0310] unsubstituted or substituted phenyl and
  • [0311] unsubstituted or substituted 4-6 membered heterocyclyl;
  • [0312]  preferably H, chloro, fluoro, bromo, amino, hydroxy, methyl, ethyl, propyl, oxo, dimethylamino, aminosulfonyl, cyclopropyl, cyano, hydroxymethyl, nitro, propenyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, carboxymethyl, morpholinylethylamino, propynyl, unsubstituted or substituted phenyl and unsubstituted or substituted heteroaryl selected from thienyl, furanyl, pyridyl, imidazolyl, and pyrazolyl;
• [0313] wherein R⁴ is selected from a direct bond, C_1-4-alkyl, and

[0314]

• • [0315] preferably direct bond, ethyl, butyl, and

[0316]

• [0317] wherein R^e and R^f are independently selected from H and C_1-2-haloalkyl,
  • [0318] preferably —CF₃;
• [0319] wherein R⁶ is H or C_1-2-alkyl, preferably H or methyl; and
• [0320] wherein R⁷ is selected from H, C_1-3-alkyl, optionally substituted phenyl-C_1-3-alkyl, 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyl-C₁-C₃-alkyl, C_1-3-alkoxy-C_1-2-alkyl and C_1-3-alkoxy-C_1-3-alkoxy-C_1-3-alkyl.

[0322]

• [0323] wherein A⁵ is selected from S, O and NR⁶;
• [0324] wherein R is selected from
  • [0325] unsubstituted or substituted 9- or 10-membered fused nitrogen-containing heteroaryl,
  • [0326] preferably indolyl, isoindolyl, indazolyl, quinolyl, isoquinolyl, naphthyridinyl and quinozalinyl,
  • [0327] more preferably 5-indazolyl and 6-indazolyl, even more preferably 6-indazolyl,
  • [0328]  where R is substituted with one or more substituents selected from halo, amino, hydroxy, C_1-6-alkyl, C_1-6-haloalkyl, C_1-6-alkoxy, C_1-6-alkylamino-C_2-4-alkynyl, C_1-6-alkylamino-C_1-6-alkoxy, C_1-6-alkylamino-C_1-6-alkoxy-C_1-6-alkoxy, optionally substituted heterocyclyl-C_2-4-alkynyl, and optionally substituted heterocyclylalkoxy,
  • [0329] preferably chloro, fluoro, amino, hydroxy, methyl, ethyl, propyl, trifluoromethyl, dimethylaminopropynyl, 1-methylpiperdinylmethoxy, dimethylaminoethoxyethoxy, methoxy and ethoxy;
• [0330] wherein R¹ is selected from unsubstituted or substituted aryl,
  • [0331] preferably phenyl, tetrahydronaphthyl, indanyl, indenyl and naphthyl,
  • [0332] cycloalkyl,
  • [0333] preferably cyclohexyl,
  • [0334] 4-6 membered heterocyclyl,
  • [0335] preferably isoxazolyl, pyrazolyl, thiazolyl, thiadiazolyl, thienyl, pyridyl, pyrimidinyl and pyridazinyl, and
  • [0336] 9-10 membered bicyclic and 13-14 membered tricyclic heterocyclyl,
  • [0337] preferably 1,2-dihydroquinolyl, 1,2,3,4-tetrahydro-isoquinolyl, isoquinolyl, quinolyl, indolyl, isoindolyl, 2,3-dihydro-1H-indolyl, naphthyridinyl, quinozalinyl, 2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluorenyl, 5,6,7-trihydro-1,2,4-triazolo(3,4-a]isoquinolyl, benzo[d]isothiazolyl, tetrahydroquinolinyl, indazolyl, 2,1,3-benzothiadiazolyl, benzodioxanyl, benzothienyl, benzofuryl, benzimidazolyl, benzoxazolyl and benzthiazolyl;
  • [0338]  wherein R¹ is substituted with one or more substituents selected from halo, C_1-4-alkyl, optionally substituted C_3-6-cycloalkyl, optionally substituted phenyl, optionally substituted phenyl-C₁-C₄-alkylenyl, C_1-2-haloalkoxy, optionally substituted phenyloxy, optionally substituted 4-6 membered heterocyclyl-C₁-C₄-alkylenyl, optionally substituted 4-6 membered heterocyclyl-C₂-C₄-alkenylenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyloxy, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkoxy, optionally substituted 4-6 membered heterocyclylsulfonyl, optionally substituted 4-6 membered heterocyclylamino, optionally substituted 4-6 membered heterocyclylcarbonyl, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkylcarbonyl, C_1-2-haloalkyl, C_1-4-aminoalkyl, nitro, amino, hydroxy, cyano, aminosulfonyl, C_1-2-alkylsulfonyl, halosulfonyl, C_1-4-alkylcarbonyl, C_1-3-alkylamino-C_1-3-alkyl, C_1-3-alkylamino-C_1-3-alkoxy, C_1-3-alkylamino-C_1-3-alkoxy-C_1-3-alkoxy, C_1-4-alkoxycarbonyl, C_1-4-alkoxycarbonylamino-C_1-4-alkyl, C_1-4-hydroxyalkyl,

[0339]

• • [0340]  and C_1-4-alkoxy,
  • [0341] preferably bromo, chloro, fluoro, iodo, nitro, amino, cyano, aminoethyl, Boc-aminoethyl, hydroxy, aminosulfonyl, 4-methylpiperazinylsulfonyl, cyclohexyl, phenyl, phenylmethyl, morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinylpropyl, morpholinylpropyl, methylpiperidinylmethyl, morpholinylethyl, 1-(4-morpholinyl)-2,2-dimethylpropyl, piperidinylethyl, piperidinylmethyl, piperidinylpropyl, pyrrolidinylpropyl, pyrrolidinylpropenyl, pyrrolidinylbutenyl, fluorosulfonyl, methylsulfonyl, methylcarbonyl, piperidinylmethylcarbonyl, methylpiperazinylcarbonylethyl, methoxycarbonyl, 3-ethoxycarbonyl-2-methyl-fur-5-yl, methylpiperazinyl, methylpiperidyl, 1-methyl-(1,2,3,6-tetrahydropyridyl), imidazolyl, morpholinyl, 4-trifluoromethyl-1-piperidinyl, hydroxybutyl, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, sec-butyl, trifluoromethyl, pentafluoroethyl, nonafluorobutyl, dimethylaminopropyl, 1,1-di(trifluoromethyl)-1-hydroxymethyl, 1,1-di(trifluoromethyl)-1-(piperidinylethoxy)methyl, 1,1-di(trifluoromethyl)-1-(methoxyethoxyethoxy)methyl, 1-hydroxyethyl, 2-hydroxyethyl, trifluoromethoxy, 1-aminoethyl, 2-aminoethyl, 1-(N-isopropylamino)ethyl, 2-(N-isopropylamino)ethyl, dimethylaminoethoxy, 4-chlorophenoxy, phenyloxy, 1-methylpiperdin-4-yloxy, isopropoxy, methoxy and ethoxy;
• [0342] wherein R² is one or more substituents independently selected from
  • [0343] H,
  • [0344] halo,
  • [0345] hydroxy,
  • [0346] amino,
  • [0347] C_1-6-alkyl,
  • [0348] C_1-6-haloalkyl,
  • [0349] C_1-6-alkoxy,
  • [0350] C_1-2-alkylamino,
  • [0351] aminosulfonyl,
  • [0352] C_3-6-cycloalkyl,
  • [0353] cyano,
  • [0354] C_1-2-hydroxyalkyl,
  • [0355] nitro,
  • [0356] C_2-3-alkenyl,
  • [0357] C_2-3-alkynyl,
  • [0358] C_1-6-haloalkoxy,
  • [0359] C_1-6-carboxyalkyl,
  • [0360] 5-6-membered heterocyclyl-C_1-6-alkylamino,
  • [0361] unsubstituted or substituted phenyl and
  • [0362] unsubstituted or substituted 4-6 membered heterocyclyl;
  • [0363]  preferably H, chloro, fluoro, bromo, amino, hydroxy, methyl, ethyl, propyl, oxo, dimethylamino, aminosulfonyl, cyclopropyl, cyano, hydroxymethyl, nitro, propenyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, carboxymethyl, morpholinylethylamino, propynyl, unsubstituted or substituted phenyl and unsubstituted or substituted heteroaryl selected from thienyl, furanyl, pyridyl, imidazolyl, and pyrazolyl;
• [0364] wherein R⁴ is selected from a direct bond, C_1-4-alkyl, and

[0365]

• • [0366] preferably direct bond, ethyl, butyl, and

[0367]

• [0368] wherein R^e and R^f are independently selected from H and C_1-2-haloalkyl,
  • [0369] preferably —CF₃;
• [0370] wherein R⁶ is H or C_1-2-alkyl, preferably H or methyl; and
• [0371] wherein R⁷ is selected from H, C_1-3-alkyl, optionally substituted phenyl-C_1-3-alkyl, 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyl-C₁-C₃-alkyl, C_1-3-alkoxy-C_1-2-alkyl and C_1-3-alkoxy-C_1-3-alkoxy-C_1-3-alkyl.

[0373]
wherein A⁵ is selected from S, O and NR⁶;

• [0374] wherein R is selected from
  • [0375] unsubstituted or substituted 9- or 10-membered fused nitrogen-containing heteroaryl,
  • [0376] preferably indolyl, isoindolyl, indazolyl, quinolyl, isoquinolyl, naphthyridinyl and quinozalinyl,
  • [0377] more preferably 5-indazolyl and 6-indazolyl, even more preferably 6-indazolyl,
  • [0378]  where R is substituted with one or more substituents selected from halo, amino, hydroxy, C_1-6-alkyl, C_1-6-haloalkyl, C_1-6-alkoxy, C_1-6-alkylamino-C_2-4-alkynyl, C_1-6-alkylamino-C_1-6-alkoxy, C_1-6-alkylamino-C_1-6-alkoxy-C_1-6-alkoxy, optionally substituted heterocyclyl-C_2-4-alkynyl, and optionally substituted heterocyclylalkoxy,
  • [0379] preferably chloro, fluoro, amino, hydroxy, methyl, ethyl, propyl, trifluoromethyl, dimethylaminopropynyl, 1-methylpiperdinylmethoxy, dimethylaminoethoxyethoxy, methoxy and ethoxy;
• [0380] wherein R¹ is selected from unsubstituted or substituted aryl,
  • [0381] preferably phenyl, tetrahydronaphthyl, indanyl, indenyl and naphthyl,
  • [0382] cycloalkyl,
  • [0383] preferably cyclohexyl,
  • [0384] 4-6 membered heterocyclyl,
  • [0385] preferably isoxazolyl, pyrazolyl, thiazolyl, thiadiazolyl, thienyl, pyridyl, pyrimidinyl and pyridazinyl, and
  • [0386] 9-10 membered bicyclic and 13-14 membered tricyclic heterocyclyl,
  • [0387] preferably 1,2-dihydroquinolyl, -1,2,3,4-tetrahydro-isoquinolyl, isoquinolyl, quinolyl, indolyl, isoindolyl, 2,3-dihydro-1H-indolyl, naphthyridinyl, quinozalinyl, 2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluorenyl, 5,6,7-trihydro-1,2,4-triazolo[3,4-a]isoquinolyl, tetrahydroquinolinyl, indazolyl, 2,1,3-benzothiadiazolyl, benzo[d]isothiazolyl, benzodioxanyl, benzothienyl, benzofuryl, benzimidazolyl, benzoxazolyl and benzthiazolyl;
  • [0388]  wherein R¹ is substituted with one or more substituents selected from halo, C_1-4-alkyl, optionally substituted C_3-6-cycloalkyl, optionally substituted phenyl, optionally substituted phenyl-C₁-C₄-alkylenyl, C_1-2-haloalkoxy, optionally substituted phenyloxy, optionally substituted 4-6 membered heterocyclyl-C₁-C₄-alkyl, optionally substituted 4-6 membered heterocyclyl-C₂-C₄-alkenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyloxy, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkoxy, optionally substituted 4-6 membered heterocyclylsulfonyl, optionally substituted 4-6 membered heterocyclylamino, optionally substituted 4-6 membered heterocyclylcarbonyl, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkylcarbonyl, C_1-2-haloalkyl, C_1-4-aminoalkyl, nitro, amino, hydroxy, cyano, aminosulfonyl, C_1-2-alkylsulfonyl, halosulfonyl, C_1-4-alkylcarbonyl, C_1-3-alkylamino-C_1-3-alkyl, C_1-3-alkylamino-C_1-3-alkoxy, C_1-3-alkylamino-C_1-3-alkoxy-C_1-3-alkoxy, C_1-4-alkoxycarbonyl, C_1-4-alkoxycarbonylamino-C_1-4-alkyl, C_1-4-hydroxyalkyl,

[0389]

• • [0390]  and C_1-4-alkoxy,
  • [0391] preferably bromo, chloro, fluoro, iodo, nitro, amino, cyano, aminoethyl, Boc-aminoethyl, hydroxy, aminosulfonyl, 4-methylpiperazinylsulfonyl, cyclohexyl, phenyl, phenylmethyl, morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinylpropyl, morpholinylpropyl, methylpiperidinylmethyl, morpholinylethyl, 1-(4-morpholinyl)-2,2-dimethylpropyl, piperidinylethyl, piperidinylmethyl, piperidinylpropyl, pyrrolidinylpropyl, pyrrolidinylpropenyl, pyrrolidinylbutenyl, fluorosulfonyl, methylsulfonyl, methylcarbonyl, piperidinylmethylcarbonyl, methylpiperazinylcarbonylethyl, methoxycarbonyl, 3-ethoxycarbonyl-2-methyl-fur-5-yl, methylpiperazinyl, methylpiperidyl, 1-methyl-(1,2,3,6-tetrahydropyridyl), imidazolyl, morpholinyl, 4-trifluoromethyl-1-piperidinyl, hydroxybutyl, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, sec-butyl, trifluoromethyl, pentafluoroethyl, nonafluorobutyl, dimethylaminopropyl, 1,1-di(trifluoromethyl)-1-hydroxymethyl, 1,1-di(trifluoromethyl)-1-(piperidinylethoxy)methyl, 1,1-di(trifluoromethyl)-1-(methoxyethoxyethoxy)methyl, 1-hydroxyethyl, 2-hydroxyethyl, trifluoromethoxy, 1-aminoethyl, 2-aminoethyl, 1-(N-isopropylamino)ethyl, 2-(N-isopropylamino)ethyl, dimethylaminoethoxy, 4-chlorophenoxy, phenyloxy, 1-methylpiperdin-4-yloxy, isopropoxy, methoxy and ethoxy;
• [0392] wherein R₂ is one or more substituents independently selected from
  • [0393] H,
  • [0394] halo,
  • [0395] hydroxy,
  • [0396] amino,
  • [0397] C_1-6-alkyl,
  • [0398] C_1-6-haloalkyl,
  • [0399] C_1-6-alkoxy,
  • [0400] C_1-2-alkylamino,
  • [0401] aminosulfonyl,
  • [0402] C_3-6-cycloalkyl,
  • [0403] cyano,
  • [0404] C_1-2-hydroxyalkyl,
  • [0405] nitro,
  • [0406] C_2-3-alkenyl,
  • [0407] C_2-3-alkynyl,
  • [0408] C_1-6-haloalkoxy,
  • [0409] C_1-6-carboxyalkyl,
  • [0410] 5-6-membered heterocyclyl-C_1-6-alkylamino,
  • [0411] unsubstituted or substituted phenyl and
  • [0412] unsubstituted or substituted 4-6 membered heterocyclyl;
  • [0413]  preferably H, chloro, fluoro, bromo, amino, hydroxy, methyl, ethyl, propyl, oxo, dimethylamino, aminosulfonyl, cyclopropyl, cyano, hydroxymethyl, nitro, propenyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, carboxymethyl, morpholinylethylamino, propynyl, unsubstituted or substituted phenyl and unsubstituted or substituted heteroaryl selected from thienyl, furanyl, pyridyl, imidazolyl, and pyrazolyl;
• [0414] wherein R⁴ is selected from a direct bond, C_1-4-alkyl, and

[0415]

• • [0416] preferably direct bond, ethyl, butyl, and

[0417]

• [0418] wherein R^e and R^f are independently selected from H and C_1-2-haloalkyl,
  • [0419] preferably —CF₃;
• [0420] wherein R⁶ is H or C_1-2-alkyl, preferably H or methyl; and
• [0421] wherein R⁷ is selected from H, C_1-3-alkyl, optionally substituted phenyl-C_1-3-alkyl, 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyl-C₁-C₃-alkyl, C_1-3-alkoxy-C_1-2-alkyl and C_1-3-alkoxy-C_1-3-alkoxy-C_1-3-alkyl.

[0423]
wherein A⁵ is selected from S, O and NR⁶;

• [0424] wherein R is selected from
  • [0425] unsubstituted or substituted 9- or 10-membered fused nitrogen-containing heteroaryl,
  • [0426] preferably indolyl, isoindolyl, indazolyl, quinolyl, isoquinolyl, naphthyridinyl and quinozalinyl,
  • [0427] more preferably 5-indazolyl and 6-indazolyl, even more preferably 6-indazolyl,
  • [0428]  where R is substituted with one or more substituents selected from halo, amino, hydroxy, C_1-6-alkyl, C_1-6-haloalkyl, C_1-6-alkoxy, C_1-6-alkylamino-C_2-4-alkynyl, C_1-6-alkylamino-C_1-6-alkoxy, C_1-6-alkylamino-C_1-6-alkoxy-C_1-6-alkoxy, optionally substituted heterocyclyl-C_2-4-alkynyl, and optionally substituted heterocyclylalkoxy,
  • [0429] preferably chloro, fluoro, amino, hydroxy, methyl, ethyl, propyl, trifluoromethyl, dimethylaminopropynyl, 1-methylpiperdinylmethoxy, dimethylaminoethoxyethoxy, methoxy and ethoxy;
• [0430] wherein R¹ is selected from unsubstituted or substituted aryl,
  • [0431] preferably phenyl, tetrahydronaphthyl, indanyl, indenyl and naphthyl,
  • [0432] cycloalkyl,
  • [0433] preferably cyclohexyl,
  • [0434] 4-6 membered heterocyclyl,
  • [0435] preferably isoxazolyl, pyrazolyl, thiazolyl, thiadiazolyl, thienyl, pyridyl, pyrimidinyl and pyridazinyl, and
  • [0436] 9-10 membered bicyclic and 13-14 membered tricyclic heterocyclyl,
  • [0437] preferably 1,2-dihydroquinolyl, 1,2,3,4-tetrahydro-isoquinolyl, isoquinolyl, quinolyl, indolyl, isoindolyl, 2,3-dihydro-1H-indolyl, naphthyridinyl, quinozalinyl, 2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluorenyl, 5,6,7-trihydro-1,2,4-triazolo[3,4-a]isoquinolyl, tetrahydroquinolinyl, indazolyl, benzo[d]isothiazolyl, 2,1,3-benzothiadiazolyl, benzodioxanyl, benzothienyl, benzofuryl, benzimidazolyl, benzoxazolyl and benzthiazolyl;
  • [0438]  wherein R¹ is substituted with one or more substituents selected from halo, C_1-4-alkyl, optionally substituted C_3-6-cycloalkyl, optionally substituted phenyl, optionally substituted phenyl-C₁-C₄-alkylenyl, C_1-2-haloalkoxy, optionally substituted phenyloxy, optionally substituted 4-6 membered heterocyclyl-C₁-C₄-alkyl, optionally substituted 4-6 membered heterocyclyl-C₂-C₄-alkenylenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyloxy, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkoxy, optionally substituted 4-6 membered heterocyclylsulfonyl, optionally substituted 4-6 membered heterocyclylamino, optionally substituted 4-6 membered heterocyclylcarbonyl, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkylcarbonyl, C_1-2-haloalkyl, C_1-4-aminoalkyl, nitro, amino, hydroxy, cyano, aminosulfonyl, C_1-2-alkylsulfonyl, halosulfonyl, C_1-4-alkylcarbonyl, C_1-3-alkylamino-C_1-3-alkyl, C_1-3-alkylamino-C_1-3-alkoxy, C_1-3-alkylamino-C_1-3-alkoxy-C_1-3-alkoxy, C_1-4-alkoxycarbonyl, C_1-4-alkoxycarbonylamino-C_1-4-alkyl, C_1-4-hydroxyalkyl,

[0439]

• • [0440]  and C_1-4-alkoxy,
  • [0441] preferably bromo, chloro, fluoro, iodo, nitro, amino, cyano, aminoethyl, Boc-aminoethyl, hydroxy, aminosulfonyl, 4-methylpiperazinylsulfonyl, cyclohexyl, phenyl, phenylmethyl, morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinylpropyl, morpholinylpropyl, methylpiperidinylmethyl, morpholinylethyl, 1-(4-morpholinyl)-2,2-dimethylpropyl, piperidinylethyl, piperidinylmethyl, piperidinylpropyl, pyrrolidinylpropyl, pyrrolidinylpropenyl, pyrrolidinylbutenyl, fluorosulfonyl, methylsulfonyl, methylcarbonyl, piperidinylmethylcarbonyl, methylpiperazinylcarbonylethyl, methoxycarbonyl, 3-ethoxycarbonyl-2-methyl-fur-5-yl, methylpiperazinyl, methylpiperidyl, 1-methyl-(1,2,3,6-tetrahydropyridyl), imidazolyl, morpholinyl, 4-trifluoromethyl-1-piperidinyl, hydroxybutyl, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, sec-butyl, trifluoromethyl, pentafluoroethyl, nonafluorobutyl, dimethylaminopropyl, 1,1-di(trifluoromethyl)-1-hydroxymethyl, 1,1-di(trifluoromethyl)-1-(piperidinylethoxy)methyl, 1,1-di(trifluoromethyl)-1-(methoxyethoxyethoxy)methyl, 1-hydroxyethyl, 2-hydroxyethyl, trifluoromethoxy, 1-aminoethyl, 2-aminoethyl, 1-(N-isopropylamino)ethyl, 2-(N-isopropylamino)ethyl, dimethylaminoethoxy, 4-chlorophenoxy, phenyloxy, 1-methylpiperdin-4-yloxy, isopropoxy, methoxy and ethoxy;
• [0442] wherein R² is one or more substituents independently selected from
  • [0443] H,
  • [0444] halo,
  • [0445] hydroxy,
  • [0446] amino,
  • [0447] C_1-6-alkyl,
  • [0448] C_1-6-haloalkyl,
  • [0449] C_1-6-alkoxy,
  • [0450] C_1-2-alkylamino,
  • [0451] aminosulfonyl,
  • [0452] C_3-6-cycloalkyl,
  • [0453] cyano,
  • [0454] C_1-2-hydroxyalkyl,
  • [0455] nitro,
  • [0456] C_2-3-alkenyl,
  • [0457] C_2-3-alkynyl,
  • [0458] C_1-6-haloalkoxy,
  • [0459] C_1-6-carboxyalkyl,
  • [0460] 5-6-membered heterocyclyl-C_1-6-alkylamino,
  • [0461] unsubstituted or substituted phenyl and
  • [0462] unsubstituted or substituted 4-6 membered heterocyclyl;
  • [0463]  preferably H, chloro, fluoro, bromo, amino, hydroxy, methyl, ethyl, propyl, oxo, dimethylamino, aminosulfonyl, cyclopropyl, cyano, hydroxymethyl, nitro, propenyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, carboxymethyl, morpholinylethylamino, propynyl, unsubstituted or substituted phenyl and unsubstituted or substituted heteroaryl selected from thienyl, furanyl, pyridyl, imidazolyl, and pyrazolyl;
• [0464] wherein R⁴ is selected from a direct bond, C_1-4-alkyl, and

[0465]

• • [0466] preferably direct bond, ethyl, butyl, and

[0467]

• [0468] wherein R^e and R^f are independently selected from H and C_1-2-haloalkyl,
  • [0469] preferably —CF₃;
• [0470] wherein R⁶ is H or C_1-2-alkyl, preferably H or methyl; and
• [0471] wherein R⁷ is selected from H, C_1-3-alkyl, optionally substituted phenyl-C_1-3-alkyl, 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyl-C₁-C₃-alkyl, C_1-3-alkoxy-C_1-2-alkyl and C_1-3-alkoxy-C_1-3-alkoxy-C_1-3-alkyl.

[0473]
wherein A⁵ is selected from S, O and NR⁶;

• [0474] wherein R is selected from
  • [0475] unsubstituted or substituted 9- or 10-membered fused nitrogen-containing heteroaryl,
  • [0476] preferably indolyl, isoindolyl, indazolyl, quinolyl, isoquinolyl, naphthyridinyl and quinozalinyl,
  • [0477] more preferably 5-indazolyl and 6-indazolyl, even more preferably 6-indazolyl,
  • [0478]  where R is substituted with one or more substituents selected from halo, amino, hydroxy, C_1-6-alkyl, C_1-6-haloalkyl, C_1-6-alkoxy, C_1-6-alkylamino-C_2-4-alkynyl, C_1-6-alkylamino-C_1-6-alkoxy, C_1-6-alkylamino-C_1-6-alkoxy-C_1-6-alkoxy, optionally substituted heterocyclyl-C_2-4-alkynyl, and optionally substituted heterocyclylalkoxy,
  • [0479] preferably chloro, fluoro, amino, hydroxy, methyl, ethyl, propyl, trifluoromethyl, dimethylaminopropynyl, 1-methylpiperdinylmethoxy, dimethylaminoethoxyethoxy, methoxy and ethoxy;
• [0480] wherein R¹ is selected from unsubstituted or substituted aryl,
  • [0481] preferably phenyl, tetrahydronaphthyl, indanyl, indenyl and naphthyl,
  • [0482] cycloalkyl,
  • [0483] preferably cyclohexyl,
  • [0484] 4-6 membered heterocyclyl,
  • [0485] preferably isoxazolyl, pyrazolyl, thiazolyl, thiadiazolyl, thienyl, pyridyl, pyrimidinyl and pyridazinyl, and
  • [0486] 9-10 membered bicyclic and 13-14 membered tricyclic heterocyclyl,
  • [0487] preferably 1,2-dihydroquinolyl, 1,2,3,4-tetrahydro-isoquinolyl, isoquinolyl, quinolyl, indolyl, isoindolyl, 2,3-dihydro-1H-indolyl, naphthyridinyl, quinozalinyl, 2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluorenyl, 5,6,7-trihydro-1,2,4-triazolo[3,4-a]isoquinolyl, tetrahydroquinolinyl, indazolyl, 2,1,3-benzothiadiazolyl, benzo[d]isothiazolyl, benzodioxanyl, benzothienyl, benzofuryl, benzimidazolyl, benzoxazolyl and benzthiazolyl;
  • [0488]  wherein R¹ is substituted with one or more substituents selected from halo, C_1-4-alkyl, optionally substituted C_3-6-cycloalkyl, optionally substituted phenyl, optionally substituted phenyl-C₁-C₄-alkylenyl, C_1-2-haloalkoxy, optionally substituted phenyloxy, optionally substituted 4-6 membered heterocyclyl-C₁-C₄-alkyl, optionally substituted 4-6 membered heterocyclyl-C₂-C₄-alkenylenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyloxy, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkoxy, optionally substituted 4-6 membered heterocyclylsulfonyl, optionally substituted 4-6 membered heterocyclylamino, optionally substituted 4-6 membered heterocyclylcarbonyl, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkylcarbonyl, C_1-2-haloalkyl, C_1-4-aminoalkyl, nitro, amino, hydroxy, cyano, aminosulfonyl, C_1-2-alkylsulfonyl, halosulfonyl, C_1-4-alkylcarbonyl, C_1-3-alkylamino-C_1-3-alkyl, C_1-3-alkylamino-C_1-3-alkoxy, C_1-3-alkylamino-C_1-3-alkoxy-C_1-3-alkoxy, C_1-4-alkoxycarbonyl, C_1-4-alkoxycarbonylamino-C_1-4-alkyl, C_1-4-hydroxyalkyl,

[0489]

• • [0490]  and C_1-4-alkoxy,
  • [0491] preferably bromo, chloro, fluoro, iodo, nitro, amino, cyano, aminoethyl, Boc-aminoethyl, hydroxy, aminosulfonyl, 4-methylpiperazinylsulfonyl, cyclohexyl, phenyl, phenylmethyl, morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinylpropyl, morpholinylpropyl, methylpiperidinylmethyl, morpholinylethyl, 1-(4-morpholinyl)-2,2-dimethylpropyl, piperidinylethyl, piperidinylmethyl, piperidinylpropyl, pyrrolidinylpropyl, pyrrolidinylpropenyl, pyrrolidinylbutenyl, fluorosulfonyl, methylsulfonyl, methylcarbonyl, piperidinylmethylcarbonyl, methylpiperazinylcarbonylethyl, methoxycarbonyl, 3-ethoxycarbonyl-2-methyl-fur-5-yl, methylpiperazinyl, methylpiperidyl, 1-methyl-(1,2,3,6-tetrahydropyridyl), imidazolyl, morpholinyl, 4-trifluoromethyl-1-piperidinyl, hydroxybutyl, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, sec-butyl, trifluoromethyl, pentafluoroethyl, nonafluorobutyl, dimethylaminopropyl, 1,1-di(trifluoromethyl)-1-hydroxymethyl, 1,1-di(trifluoromethyl)-1-(piperidinylethoxy)methyl, 1,1-di(trifluoromethyl)-1-(methoxyethoxyethoxy)methyl, 1-hydroxyethyl, 2-hydroxyethyl, trifluoromethoxy, 1-aminoethyl, 2-aminoethyl, 1-(N-isopropylamino)ethyl, 2-(N-isopropylamino)ethyl, dimethylaminoethoxy, 4-chlorophenoxy, phenyloxy, 1-methylpiperdin-4-yloxy, isopropoxy, methoxy and ethoxy;
• [0492] wherein R² is one or more substituents independently selected from
  • [0493] H,
  • [0494] halo,
  • [0495] hydroxy,
  • [0496] amino,
  • [0497] C_1-6-alkyl,
  • [0498] C_1-6-haloalkyl,
  • [0499] C_1-6-alkoxy,
  • [0500] C_1-2-alkylamino,
  • [0501] aminosulfonyl,
  • [0502] C_3-6-cycloalkyl,
  • [0503] cyano,
  • [0504] C_1-2-hydroxyalkyl,
  • [0505] nitro,
  • [0506] C_2-3-alkenyl,
  • [0507] C_2-3-alkynyl,
  • [0508] C_1-6-haloalkoxy,
  • [0509] C_1-6-carboxyalkyl,
  • [0510] 5-6-membered heterocyclyl-C_1-6-alkylamino,
  • [0511] unsubstituted or substituted phenyl and
  • [0512] unsubstituted or substituted 4-6 membered heterocyclyl;
  • [0513]  preferably H, chloro, fluoro, bromo, amino, hydroxy, methyl, ethyl, propyl, oxo, dimethylamino, aminosulfonyl, cyclopropyl, cyano, hydroxymethyl, nitro, propenyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, carboxymethyl, morpholinylethylamino, propynyl, unsubstituted or substituted phenyl and unsubstituted or substituted heteroaryl selected from thienyl, furanyl, pyridyl, imidazolyl, and pyrazolyl;
• [0514] wherein R⁴ is selected from a direct bond, C_1-4-alkyl, and

[0515]

• • [0516] preferably direct bond, ethyl, butyl, and

[0517]

[0523]

• [0524] wherein A⁵ is selected from S, O and NR⁶;
• [0525] wherein A6 is selected from N and CR²;
• [0526] wherein R is selected from
  • [0527] unsubstituted or substituted 9- or 10-membered fused nitrogen-containing heteroaryl,
  • [0528] preferably indolyl, isoindolyl, indazolyl, quinolyl, isoquinolyl, naphthyridinyl and quinozalinyl,
  • [0529] more preferably 5-indazolyl and 6-indazolyl, even more preferably 6-indazolyl,
  • [0530]  where R is substituted with one or more substituents selected from halo, amino, hydroxy, C_1-6-alkyl, C_1-6-haloalkyl, C_1-6-alkoxy, C_1-6-alkylamino-C_2-4-alkynyl, C_1-6-alkylamino-C_1-6-alkoxy, C_1-6-alkylamino-C_1-6-alkoxy-C_1-6-alkoxy, optionally substituted heterocyclyl-C_2-4-alkynyl, and optionally substituted heterocyclylalkoxy,
  • [0531] preferably chloro, fluoro, amino, hydroxy, methyl, ethyl, propyl, trifluoromethyl, dimethylaminopropynyl, 1-methylpiperdinylmethoxy, dimethylaminoethoxyethoxy, methoxy and ethoxy;
• [0532] wherein R¹ is selected from unsubstituted or substituted aryl,
  • [0533] preferably phenyl, tetrahydronaphthyl, indanyl, indenyl and naphthyl,
  • [0534] cycloalkyl,
  • [0535] preferably cyclohexyl,
  • [0536] 4-6 membered heterocyclyl,
  • [0537] preferably isoxazolyl, pyrazolyl, thiazolyl, thiadiazolyl, thienyl, pyridyl, pyrimidinyl and pyridazinyl, and
  • [0538] 9-10 membered bicyclic and 13-14 membered tricyclic heterocyclyl,
  • [0539] preferably 1,2-dihydroquinolyl, 1,2,3,4-tetrahydro-isoquinolyl, isoquinolyl, quinolyl, indolyl, isoindolyl, 2,3-dihydro-1H-indolyl, naphthyridinyl, quinozalinyl, 2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluorenyl, 5,6,7-trihydro-1,2,4-triazolo[3,4-a]isoquinolyl, tetrahydroquinolinyl, indazolyl, 2,1,3-benzothiadiazolyl, benzo[d]isothiazolyl, benzodioxanyl, benzothienyl, benzofuryl, benzimidazolyl, benzoxazolyl and benzthiazolyl;
  • [0540]  wherein R¹ is substituted with one or more substituents selected from halo, C_1-4-alkyl, optionally substituted C_3-6-cycloalkyl, optionally substituted phenyl, optionally substituted phenyl-C₁-C₄-alkylenyl, C_1-2-haloalkoxy, optionally substituted phenyloxy, optionally substituted 4-6 membered heterocyclyl-C₁-C₄-alkylenyl, optionally substituted 4-6 membered heterocyclyl-C₂-C₄-alkenylenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyloxy, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkoxy, optionally substituted 4-6 membered heterocyclylsulfonyl, optionally substituted 4-6 membered heterocyclylamino, optionally substituted 4-6 membered heterocyclylcarbonyl, optionally substituted 4-6 membered heterocyclyl-C_1-4-alkylcarbonyl, C_1-2-haloalkyl, C_1-4-aminoalkyl, nitro, amino, hydroxy, cyano, aminosulfonyl, C_1-2-alkylsulfonyl, halosulfonyl, C_1-4-alkylcarbonyl, C_1-3-alkylamino-C_1-3-alkyl, C_1-3-alkylamino-C_1-3-alkoxy, C_1-3-alkylamino-C_1-3-alkoxy-C_1-3-alkoxy, C_1-4-alkoxycarbonyl, C_1-4-alkoxycarbonylamino-C_1-4-alkyl, C_1-4-hydroxyalkyl,

[0541]

• • [0542]  and C_1-4-alkoxy,
  • [0543] preferably bromo, chloro, fluoro, iodo, nitro, amino, cyano, aminoethyl, Boc-aminoethyl, hydroxy, aminosulfonyl, 4-methylpiperazinylsulfonyl, cyclohexyl, phenyl, phenylmethyl, morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinylpropyl, morpholinylpropyl, methylpiperidinylmethyl, morpholinylethyl, 1-(4-morpholinyl)-2,2-dimethylpropyl, piperidinylethyl, piperidinylmethyl, piperidinylpropyl, pyrrolidinylpropyl, pyrrolidinylpropenyl, pyrrolidinylbutenyl, fluorosulfonyl, methylsulfonyl, methylcarbonyl, piperidinylmethylcarbonyl, methylpiperazinylcarbonylethyl, methoxycarbonyl, 3-ethoxycarbonyl-2-methyl-fur-5-yl, methylpiperazinyl, methylpiperidyl, 1-methyl-(1,2,3,6-tetrahydropyridyl), imidazolyl, morpholinyl, 4-trifluoromethyl-1-piperidinyl, hydroxybutyl, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, sec-butyl, trifluoromethyl, pentafluoroethyl, nonafluorobutyl, dimethylaminopropyl, 1,1-di(trifluoromethyl)-1-hydroxymethyl, 1,1-di(trifluoromethyl)-1-(piperidinylethoxy)methyl, 1,1-di(trifluoromethyl)-1-(methoxyethoxyethoxy)methyl, 1-hydroxyethyl, 2-hydroxyethyl, trifluoromethoxy, 1-aminoethyl, 2-aminoethyl, 1-(N-isopropylamino)ethyl, 2-(N-isopropylamino)ethyl, dimethylaminoethoxy, 4-chlorophenoxy, phenyloxy, 1-methylpiperdin-4-yloxy, isopropoxy, methoxy and ethoxy;
• [0544] wherein R² is one or more substituents independently selected from
  • [0545] H,
  • [0546] halo,
  • [0547] hydroxy,
  • [0548] amino,
  • [0549] C_1-6-alkyl,
  • [0550] C_1-6-haloalkyl,
  • [0551] C_1-6-alkoxy,
  • [0552] C_1-2-alkylamino,
  • [0553] aminosulfonyl,
  • [0554] C_3-6-cycloalkyl,
  • [0555] cyano,
  • [0556] C_1-2-hydroxyalkyl,
  • [0557] nitro,
  • [0558] C_2-3-alkenyl,
  • [0559] C_2-3-alkynyl,
  • [0560] C_1-6-haloalkoxy,
  • [0561] C_1-6-carboxyalkyl,
  • [0562] 5-6-membered heterocyclyl-C_1-6-alkylamino,
  • [0563] unsubstituted or substituted phenyl and
  • [0564] unsubstituted or substituted 4-6 membered heterocyclyl;
  • [0565]  preferably H, chloro, fluoro, bromo, amino, hydroxy, methyl, ethyl, propyl, oxo, dimethylamino, aminosulfonyl, cyclopropyl, cyano, hydroxymethyl, nitro, propenyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, carboxymethyl, morpholinylethylamino, propynyl, unsubstituted or substituted phenyl and unsubstituted or substituted heteroaryl selected from thienyl, furanyl, pyridyl, imidazolyl, and pyrazolyl;
• [0566] wherein R⁴ is selected from a direct bond, C_1-4-alkyl, and

[0567]

• • [0568] preferably direct bond, ethyl, butyl, and

[0569]

• [0570] wherein R^e and R^f are independently selected from H and C_1-2-haloalkyl,
  • [0571] preferably —CF₃;
• [0572] wherein R⁶ is H or C_1-2-alkyl, preferably H or methyl;
• [0573] wherein R⁷ is selected from H, C_1-3-alkyl, optionally substituted phenyl-C_1-3-alkyl, 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyl-C₁-C₃-alkyl, C_1-3-alkoxy-C_1-2-alkyl and C_1-3-alkoxy-C_1-3-alkoxy-C_1-3-alkyl; and wherein
  • [0574] a) R¹⁰ is

[0575]

• • [0576]  
  • [0577]  R¹¹ is —NHR, R¹² is H, and R¹³ is H; or
  • [0578] b) R¹⁰ is —NHR, R¹¹ is

[0579]

• • [0580]  R¹² is H, and R¹³ is H; or
  • [0581] c) R¹⁰ is H, R¹¹ is —NHR, R¹² is

[0582]

• • [0583]  and R¹³ is H; or
  • [0584] d) R¹⁰ is H, R¹¹ is

[0585]

• • [0586]  R¹² is —NHR, and R¹³ is H; or
  • [0587] e) R¹⁰ is H, R¹¹ is H, R¹² is

[0588]

• • [0589]  and R¹³ is —NHR; or
  • [0590] f) R¹⁰ is H, R¹¹ is H, R is —NHR, and R¹³ is

[0591]

[0739]
wherein each of A¹ and A² is independently C, CH or N;

• [0740] wherein ring A is selected from
  • [0741] a) 5- or 6-membered partially saturated heterocyclyl,
  • [0742] b) 5- or 6-membered heteroaryl,
  • [0743] c) 9-, 10- or 11-membered fused partially saturated heterocyclyl,
  • [0744] d) 9- or 10-membered fused heteroaryl,
  • [0745] e) aryl, and
  • [0746] f) 4-, 5- or 6-membered cycloalkenyl;

[0748]

• [0749] wherein Z is oxygen or sulfur;
• [0750] wherein R is selected from
  • [0751] a) substituted or unsubstituted 4-6 membered heterocyclyl,
  • [0752] b) substituted aryl, and
  • [0753] c) substituted or unsubstituted fused 9-14-membered bicyclic or tricyclic heterocyclyl;
    • [0754] wherein substituted R is substituted with one or more substituents independently selected from halo, —OR³, —SR³, —SO₂R³, —CO₂R³, —CONR³R³, —COR³, —NR³R³, —SO₂NR³R³, —NR³C(O)OR³, —NR³C(O)R³, cycloalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, nitro, alkylaminoalkoxyalkoxy, cyano, alkylaminoalkoxy, lower alkyl substituted with R², lower alkenyl substituted with R², and lower alkynyl substituted with R²;
• [0755] wherein R¹ is selected from
  • [0756] a) substituted or unsubstituted 6-10 membered aryl,
  • [0757] b) substituted or unsubstituted 4-6 membered heterocyclyl,
  • [0758] c) substituted or unsubstituted 9-14 membered bicyclic or tricyclic heterocyclyl,
  • [0759] d) cycloalkyl, and
  • [0760] e) cycloalkenyl,
    • [0761] wherein substituted R¹ is substituted with one or more substituents independently selected from halo, —OR³, —SR³, —CO₂R³, —CONR³R³, —COR³, —NR³R³, —NH(C₁-C₄ alkylenylR¹⁴), —SO₂R³, —SO₂NR³R³, —NR₃C(O)OR³, —NR³C(O)R³, optionally substituted cycloalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, halosulfonyl, cyano, alkylaminoalkoxy, alkylaminoalkoxyalkoxy, nitro, lower alkyl substituted with R², lower alkenyl substituted with R², and lower alkynyl substituted with R²;
• [0762] wherein R² is one or more substituents independently selected from H, halo, —OR³, oxo, —SR³, —CO₂R³, —COR³, —CONR³R³, —NR³R³, —SO₂NR³R³, —NR³C(O)OR³, —NR³C(O)R³, cycloalkyl, optionally substituted phenylalkylenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted heteroarylalkylenyl, optionally substituted phenyl, lower alkyl, cyano, lower hydroxyalkyl, lower carboxyalkyl, nitro, lower alkenyl, lower alkynyl, lower aminoalkyl, lower alkylaminoalkyl and lower haloalkyl;
• [0763] wherein R³ is selected from H, lower alkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted C₃-C₆-cycloalkyl, optionally substituted phenylalkyl, optionally substituted 4-6 membered heterocyclylalkyl, optionally substituted C₃-C₆ cycloalkylalkyl, and lower haloalkyl; wherein R⁴ is selected from a direct bond, C_2-4-alkylenyl, C_2-4-alkenylenyl and C_2-4-alkynylenyl, where one of the CH₂ groups may be substituted with an oxygen atom or an —NH—, wherein R⁴ is optionally substituted with hydroxy;
• [0764] wherein R⁵ is selected from H, lower alkyl, optionally substituted phenyl and lower aralkyl;
• [0765] wherein R¹⁴ is selected from H, phenyl, 4-6 membered heterocyclyl and C₃-C₆ cycloalkyl;
• [0766] and pharmaceutically acceptable derivatives thereof; provided R is not unsubstituted 2-thienyl, 2-pyridyl or 3-pyridyl.
  Combinations

General Synthetic Procedures

[0785]

[0791]

[0795]

[0797]

[0799]

[0801]

[0803]

[0805]

[0807]

[0809]

[0811]

[0813]

[0815]

[0817]

[0819]

[0823]

[0826]

[0830]

[0833]

[0835]

[0837]

[0839]

[0841]

[0843]

[0845]

[0847]

[0849]

[0851]

[0853]

[0855]

[0857]

[0883]
The invention expressly includes all tautomeric forms of the compounds described herein.

Preparation I—3-nitro-5-trifluoromethyl-phenol

Preparation II—1-Boc-4-(3-nitro-5-trifluoromethyl-phenoxy)-piperidine

Preparation III—1-Boc-4-(3-amino-5-trifluoromethyl-phenoxy)-piperidine

Preparation IV—1-Boc-4-{3-[(2-fluoro-pyridine-3-carbonyl)-amino]-5-trifluoromethyl-phenoxy}-piperidine

Preparation V—1-Boc-4-{3-[(2-chloro-pyridine-3-carbonyl)-amino]-5-trifluoromethyl-phenoxy}-piperidine

Preparation VI—1-Boc-2-{3-[(2-fluoro-pyridine-3-carbonyl)-amino]-5-trifluoromethyl-phenoxymethyl}-pyrrolidine

Preparation VII—2-(3-nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine

Preparation VIII—1-methyl-2-(3-nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine

Preparation IX—4-tert-butyl-3-nitro-phenylamine

Preparation X—N-(3-bromo-5-trifluoromethyl-phenyl)-acetamide

Preparation XI—N-[3-(3-piperidin-1-yl-propyl)-5-trifluoromethyl-phenyl]-acetamide

Preparation XII—3-(3-piperidin-1-yl-propyl)-5-trifluoromethyl-phenylamine

Preparation XIII—3,3-Dimethyl-6-nitro-1-piperidin-4-ylmethyl-2,3-dihydro-1H-indole

Preparation XIV—N-[3-(3-morpholin-4-yl-propyl)-5-trifluoromethyl-phenyl]-acetamide

Preparation XV—3-(3-morpholin-4-yl-propyl)-5-trifluoromethyl-phenylamine

Preparation XVI—1-methyl-4-methylene-piperidine

Preparation XVII—N-[3-(1-methylpiperidin-4-yl)-5-trifluoromethyl-phenyl]-acetamide

Preparation XVIII—3-(1-methylpiperidin-4-yl)-5-trifluoromethyl-phenylamine

Preparation XIX—2-(1-methylpiperidin-4-yloxy)-4-pyridylcarbonitrile

Preparation XX—[2-(1-methylpiperidin-4-yloxy)-pyridin-4-yl]methylamine bis hydrochloride

Preparation XXI—2-(2-morpholin-4-yl-ethoxy)-4-pyridylcarbonitrile

Preparation XXII—2-morpholin-4-yl-propanol

Preparation XXIII—2-(2-morpholin-4-yl-propoxy)-4-pyridylcarbonitrile

Preparation XXIV—2-(1-Methyl-pyrrolidin-2-ylmethoxy)-4-pyridylcarbonitrile

Preparation XXV—2-(3-morpholin-4-yl-propylamino)-4-pyridylcarbonitrile

Preparation XXVI—5-Nitro-2-pentafluoroethylphenol

Preparation XXVII—2-tert-Butyl-5-nitro-aniline

Preparation XXVIII—2-tert-Butyl-5-nitrophenol

Preparation XXIX—1-methylpiperidine-4-carboxylic acid ethyl ester

Preparation XXX—N-[4-tert-Butyl-3-(1-methyl-piperidin-4-ylmethoxy)-phenyl]-2-chloro-nicotinamide

Preparation XXXI—1-[2-(2-tert-Butyl-5-nitro-phenoxy)-ethyl]-piperidine

Preparation XXXII—1-Boc-Piperidine-4-carboxylic acid ethyl ester

Preparation XXXIII—1-Boc-4-hydroxymethyl-piperidine

Preparation XXXIV—1-Boc-4-Methylsulfonyloxymethyl-piperidine

Preparation XXXV—1-Boc-4-(3-nitro-6-pentafluoroethyl-phenoxymethyl)-piperidine

Preparation XXXVI—4-(3-nitro-6-pentafluoroethyl-phenoxymethyl)-piperidine

Preparation XXXVII—1-methyl-4-(3-nitro-6-pentafluoroethyl-phenoxymethyl)-piperidine

Preparation XXXVIII—1-Isopropyl-4-(5-nitro-2-pentafluoroethyl-phenoxymethyl)-piperidine

Preparation XXXIX—3,3-Dimethyl-1-(1-methyl-piperidin-4-ylmethyl)-6-nitro-2,3-dihydro-1H-indole

Preparation XL—(S) 2-(5-Nitro-2-pentafluoroethyl-phenoxymethyl)-oxirane

Preparation XLI—(S) 2-Chloro-N-[3-(2-hydroxy-3-pyrrolidin-1-yl-propoxy)-4-pentafluoroethyl-phenyl]-nicotinamide

Preparation XLII—5-nitro-2-trifluoromethylanisole

Preparation XLIII—1-[2-(5-nitro-2-trifluoromethylphenoxy)ethyl]pyrrolidine

Preparation XLIV—1-[2-(5-Nitro-2-pentafluoroethyl-phenoxy)-ethyl]-piperidine

Preparation XLV—3-(1-Boc-pyrrolidin-2-ylmethoxy)-4-pentafluoroethyl-phenylamine

Preparation XLVI—2-Chloro-N-[3-(2-pyrrolidin-1-yl-ethoxy)-4-trifluoromethyl-phenyl]-nicotinamide

Preparation XLVII—(R) Acetic acid 2-(5-nitro-2-pentafluoroethyl-phenoxy)-1-pyrrolidin-1-ylmethyl-ethyl ester

Preparation XLVIII—(R) 2-Chloro-N-[3-(2-hydroxy-2-pyrrolidin-1-yl-propoxy)-4-pentafluoroethyl-phenyl]-nicotinamide

Preparation XLIX—2-Dimethylamino-1-(3,3-dimethyl-6-nitro-2,3-dihydro-indol-1-yl)-ethanone

Preparation L—1-(6-Amino-3,3-dimethyl-2,3-dihydro-indol-1-yl)-2-(N-Boc-amino)-ethanone

Preparation LI—2-Boc-4,4-dimethyl-7-nitro-1,2,3,4-tetrahydro-isoquinoline

Preparation LII—2-Bromo-N-(4-methoxy-benzyl)-5-nitro-benzamide

Preparation LIII—2-Bromo-N-(4-methoxy-benzyl)-N-(2-methyl-allyl)-5-nitro-benzamide

Preparation LIV—of 2-(4-Methoxy-benzyl)-4,4-dimethyl-7-nitro-3,4-dihydro-2H-isoquinolin-1-one

Preparation LV—4,4-Dimethyl-7-nitro-3,4-dihydro-2H-isoquinolin-1-one

Preparation LVI—4,4-Dimethyl-7-nitro-1,2,3,4-tetrahydro-isoquinoline

Preparation LVII—2-Bromomethyl-4-nitro-1-pentafluoroethyl-benzene

Preparation LVIII—1-Methyl-4-(5-nitro-2-pentafluoroethyl-benzyl)-piperazine

Preparation LIX—1-Boc-4-(5-nitro-2-pentafluoroethyl-benzyl)-piperazine.

Preparation LX—(4-Boc-piperazin-1-yl)-(3-nitro-5-trifluoromethyl-phenyl)-methanone

Preparation LXI—1-Boc-4-(3-nitro-5-trifluoromethyl-benzyl)-piperazine

Preparation LXII—2-Ethyl-4-aminomethyl pyridine

Preparation LXIII—N-Boc-[2-(4-morpholin-4-yl-butyl)-pyrimidin-4-ylmethyl]-amine

Preparation LXIV—2-fluoronicotinic acid

Preparation LXV—4-cyano-2-methoxypyridine

Preparation LXVI—(2-methoxypyridin-4-yl)methylamine

Preparation LXVII—2-(4-Amino-phenyl)-2-methyl-propionic acid methyl ester

Preparation LXVIII—1-(2-tert-Butyl-phenyl)-4-methyl-piperazine

Preparation LXIX—3-(1-Methyl-1,2,3,6-tetrahydro-pyridin-4-yl)-5-trifluoromethyl-phenylamine

Preparation LXX—3,3-Dimethyl-6-nitro-2,3-dihydro-benzo[d]isothiazole 1,1-dioxide

Preparation LXXI—3-(1-Methyl-1,2,3,4-tetrahydro-pyridin-4-yl)-5-trifluoromethyl-phenylamine

Preparation LXXII—Trifluoromethylsulfonic acid 1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl ester

Preparation LXXIII—3-(5,5-Dimethyl-[1,3,2]dioxaborinan-2-yl)-5-trifluoromethyl-phenylamine

Preparation LXXIV—1-Boc-3-Hydroxymethyl-azetidine

Preparation LXXV—1-Boc-3-(3-nitro-5-trifluoromethyl-phenoxymethyl)-azetidine

Preparation LXXVI—2,2-Dimethyl-6-nitro-3,4-dihydro-2H-benzo[1,4]oxazine

Preparation LXXVII—2,2,4-Trimethyl-6-nitro-4H-benzo[1,4]oxazin-3-one

Preparation LXXVIII—2-Bromo-N-(2-hydroxy-5-nitro-phenyl)-2-methyl-propionamide

Preparation LXXIX—2,2-Dimethyl-6-nitro-4H-benzo[1,4]oxazin-3-one

Preparation LXXX—4-[1-(2-Bromo-4-nitro-phenyl)-1-methyl-ethyl]-1-methyl-pyridinium iodide

Preparation LXXXI—4-[l-(2-Bromo-4-nitro-phenyl)-1-methyl-ethyl]-1-methyl-1,2,3,6-tetrahydro-pyridine

Preparation LXXXII—1-Methyl-4-[1-methyl-1-(4-nitro-phenyl)-ethyl]-pyridinium iodide

Preparation LXXXIII—1-Methyl-4-(4-nitro-benzyl)-1,2,3,6-tetrahydro-pyridine

Preparation LXXXIV—1-Boc-4-formylpiperidine

Preparation LXXXV 2-Chloro-4-cyanopyridine

Preparation LXXXVI 4-(2-tert-Butyl-5-nitro-phenyl)-but-3-en-1-ol

Preparation LXXXVII 4-(2-tert-Butyl-5-nitro-phenyl)-but-3-enal

Preparation LXXXVIII 1-[4-(2-tert-Butyl-5-nitro-phenyl)-but-3-enyl]-pyrrolidine

Preparation LXXXVIV N-Boc-(2-chloropyrimidin-4-yl)-methylamine

EXAMPLE 1

[1279]

N-(4-Chlorophenyl)[2-(6-quinolylamino)(3-pyridyl)]carboxamide

Step A—Preparation of 2-(6-quinolylamino)pyridine-3-carboxylic acid

Step B—Preparation of N-(4-chlorophenyl)[2-(6-quinolylamino) (3-pyridyl)]carboxamide

EXAMPLE 2

[1282]

N-(4-Chlorophenyl)[2-(5-isoquinolylamino)(3-pyridyl)]carboxamide

EXAMPLE 3

[1284]

N-(4-Chlorophenyl)[2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

Step A—Preparation of (2-chloro(3-pyridyl))-N-(4-chlorophenyl)carboxamide

Step B—Preparation of N-(4-chlorophenyl)[2-(1H-indazol-5-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 4

[1287]

N-(4-Chlorophenyl)[2-(1H-indazol-5-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 5

[1289]

2-(1H-Indazol-6-ylamino)-N-(4-isopropyl-phenyl)nicotinamide

Step A: Preparation of (2-chloro(3-pyridyl))-N-(4-isopropylphenyl)carboxamide

Step B: Preparation of [2-(1H-indazol-6-ylamino)(3-pyridyl)]-N-[4-(methylethyl)phenyl]carboxamide hydrochloride

EXAMPLE 6

[1293]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[3-(methylethyl)phenyl]carboxamide

EXAMPLE 7

[1295]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[4-(methylpropyl)phenyl]carboxamide

EXAMPLE 8

[1297]

N-[4-(tert-Butyl)phenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 9

[1299]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[3-(trifluoromethyl)phenyl]carboxamide

EXAMPLE 10

[1301]

N-[3-(tert-Butyl)phenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 11

[1303]

[2-(Benzotriazol-6-ylamino)(3-pyridyl)]-N-[4-(tert-butyl)phenyl]carboxamide

EXAMPLE 12

[1305]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-(3-phenylpyrazol-5-yl)carboxamide

EXAMPLE 13

[1307]

N-3-aminosulfonyl(4-chloro-phenyl)[2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 14

[1309]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-(4-methyl-2-oxo-1,2-dihydroquinol-7-yl)carboxamide

EXAMPLE 15

[1311]

N-[4-(Methylethyl)phenyl]{2-[(4-methyl-2-oxo(7-hydroquinolyl))amino](3-pyridyl)}carboxamide

EXAMPLE 16

[1313]

N-[5-(tert-Butyl)isoxazol-3-yl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 17

[1315]

N-[5-(tert-Butyl)-1-methylpyrazol-3-yl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 18

[1317]

N-[4-(tert-Butyl)(1,3-thiazol-2-yl)][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 19

[1319]

N-[5-(tert-Butyl)(1,3,4-thiadiazol-2-yl)][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 20

[1321]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[4-(1,1,2,2,3,3,4,4,4-nonafluorobutyl)phenyl]carboxamide

Step A: Preparation of 4-(1,1,2,2,3,3,4,4,4-nonafluorobutyl) phenylamine

Step B: Preparation of [2-(1H-indazol-6-ylamino)(3-pyridyl)]-N-[4-(1,1,2,2,3,3,4,4,4-nonafluorobutyl)-phenyl]carboxamide

EXAMPLE 21

[1324]

{2-[(1-Methyl(1H-indazol-6-yl))amino](3-pyridyl)}-N-[4-(methylethyl)phenyl]carboxamide

Step A: Preparation of 1-methyl-6-amino-1H-indazole

Step B Preparation of {2-[(1-methyl(1H-indazol-6-yl))amino](3-pyridyl)}-N-[4-(methylethyl)phenyl]-carboxamide

EXAMPLE 22

[1327]

N-[4-(tert-Butyl)phenyl]{2-[(7-bromo(1H-indazol-6-yl))amino](3-pyridyl)}carboxamide

EXAMPLE 23

[1329]

2-(1H-Indazol-6-ylamino)-N-[4-tert-butyl-3-(1,2,3,6-tetrahydropyridin-4-yl)phenyl]nicotinamide

Step A: Preparation of 2-bromo-1-tert-butyl-4-nitrobenzene

Step B: Preparation of 4-(2-tert-butyl-5-nitrophenyl)pyridine

Step C: Preparation of 4-(2-tert-butyl-5-nitrophenyl)-1-methylpyridinium

Step D: Preparation of 4-tert-butyl-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)aniline

Step E Preparation of 2-(1H-indazol-6-ylamino)-N-[4-tert-butyl-3-(1,2,3,6-tetrahydropyridin-4-yl)phenyl]nicotinamide

EXAMPLE 24

[1335]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-{4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl}carboxamide

Step A: Preparation of 2-(1H-indazol-6-ylamino)pyridine-3-carboxylic acid

Step B: Preparation of [2-(1H-indazol-6-ylamino)(3-pyridyl)]-N-{4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl}carboxamide

EXAMPLE 25

[1339]

N-[5-(tert-Butyl)-2-methoxyphenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 26

[1341]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-{6-[4-(trifluoromethyl)piperidyl](3-pyridyl)}carboxamide

EXAMPLE 27

[1343]

2-(1H-Indazol-6-ylamino)-N-(1-oxo-1,2,3,4-tetrahydro-isoquinolin-7-yl)-nicotinamide

EXAMPLE 28

[1345]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[4-(methylethoxy)phenyl]carboxamide

EXAMPLE 29

[1347]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-{4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl}carboxamide

Step A: Preparation of [1-(4-amino-phenyl)-ethyl]carbamic acid tert-butyl ester

Step B: Preparation of [2-(1H-indazol-6-ylamino)(3-pyridyl)]-N-{4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl}carboxamide

EXAMPLE 30

[1350]

N-(4-{(1S)-1-[(Methylethyl)amino]ethyl}phenyl)[2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 31

[1352]

N-[4-(tert-Butyl)-3-(4-methylpiperazinyl)phenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

Step A: Preparation of 1-[2-(tert-butyl)-5-aminophenyl]-4-methylpiperazine

Step B: Preparation of N-[4-(tert-butyl)-3-(4-methylpiperazinyl)phenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 32

[1355]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[3-(4-methylpiperazinyl)phenyl]carboxamide

Step A: Preparation of 1-(5-aminophenyl)-4-methylpiperazine

Step B: Preparation of [2-(1H-indazol-6-ylamino)(3-pyridyl)]-N-[3-(4-methylpiperazinyl)phenyl]carboxamide

EXAMPLE 33

[1358]

N-[4-(tert-Butyl)-2-(4-methylpiperazinyl)phenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

Step A: Preparation of 4-(tert-butyl)-2-(4-methylpiperazinyl)phenylamine

Step B: Preparation of N-[4-(tert-butyl)-2-(4-methylpiperazinyl)phenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 34

[1361]

N-{2-[2-(Dimethylamino)ethoxy]-5-(tert-butyl)phenyl}[2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

Step A: Preparation of {2-[4-(tert-butyl)-2-aminophenoxy]Ethyl}dimethylamine

Step B: Preparation of N-{2-[2-(dimethylamino)ethoxy]-5-(tert-butyl)phenyl}[2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 35

[1364]

N-{3-[2-(Dimethylamino)ethoxy]phenyl}[2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

Step A: Preparation of [2-(2-aminophenoxy)ethyl]-dimethylamine

Step B: Preparation of N-{3-[2-(Dimethylamino)ethoxy]phenyl}[2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 36

[1367]

N-(3-Hydroxy-4-methoxyphenyl)[2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 37

[1369]

N-{3-[2-(Dimethylamino)ethoxy]-4-methoxyphenyl}[2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 38

[1371]

[2-(1H-Indazol-6-ylamino) (3-pyridyl)]-N-[4-methoxy-3-(1-methyl(4-piperidyl)oxy)phenyl]carboxamide

EXAMPLE 39

[1373]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-(5,6,7-trihydro-1,2,4-triazolo[3,4-a]isoquinolin-2-yl)carboxamide

Step A: Preparation of 2-amino-5,6,7-trihydro-1,2,4-triazolo[3,4-a]isoguinoline

Step B: Preparation of [2-(1H-indazol-6-ylamino)(3-pyridyl)]-N-(5,6,7-trihydro-1,2,4-triazolo[3,4-a]isoquinolin-2-yl)carboxamide

EXAMPLE 40

[1376]

[2-({3-[2-(Dimethylamino)ethoxy](1H-indazol-6-yl)}amino)(3-pyridyl)]-N-[4-(tert-butyl)phenyl]carboxamide

Step A: Preparation of 6-nitro-1-Boc-2-hydroindazol-3-one

Step B: Preparation of [2-({3-[2-(dimethylamino)ethoxy](1H-indazol-6-yl)}amino)(3-pyridyl)]-N-[4-(tert-butyl)phenyl]carboxamide

EXAMPLE 41

[1379]

N-[3,3-Dimethyl-1-(4-piperidylmethyl)indolin-6-yl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

Step A: Preparation of tert-butyl 4-[(6-nitro-3,3-dimethylindolinyl)methyl]piperidinecarboxylate

Step B: Preparation of 3,3-dimethyl-1-piperidin-4-ylmethyl-2,3-dihydro-1H-indol-6-ylamine

Step C: Preparation of N-[3,3-dimethyl-1-(4-piperidylmethyl)indolin-6-yl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 42

[1383]

N-[3,3-Dimethyl-1-(1-methyl-piperidin-4-ylmethyl)-2,3-dihydro-1H-indol-6-yl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 43

[1385]

2-(1H-Indazol-6-ylamino)-N-(4-phenoxy-phenyl)-nicotinamide

Step A: Preparation of (2-chloro-(3-pyridyl))-N-(4-phenoxyphenyl)carboxamide

Step B: Preparation of [2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-(4-phenoxyphenyl)carboxamide

EXAMPLE 44

[1389]

[2-(1H-Indazol-5-ylamino)(3-pyridyl)]-N-(4-phenoxyphenyl)carboxamide

EXAMPLE 45

[1391]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-(4-phenylphenyl)carboxamide

EXAMPLE 46

[1393]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[4-(methylsulfonyl)phenyl]carboxamide

EXAMPLE 47

[1395]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[1-(1-methyl(4-piperidyl))indolin-6-yl]carboxamide

Step A: Preparation of 1-(1-methyl(4-piperidyl))-6-nitroindoline

Step B: Preparation of 1-(1-methyl-4-piperidyl)indoline-6-ylamine

Step C: Preparation of [2-(1H-Indazol-6-ylamino) (3-pyridyl)]-N-[1-(1-methyl(4-piperidyl))indolin-6-yl]carboxamide

EXAMPLE 48

[1399]

N-[3,3-Dimethyl-1-(1-methyl(4-piperidyl))indolin-6-yl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

Step A: Preparation of N-(2-bromo-5-nitrophenyl)acetamide

Step B: Preparation of N-(2-bromo-5-nitrophenyl)-N-(2-methylprop-2-enyl)acetamide

Step C: Preparation of 1-(3,3-dimethyl-6-nitro-2,3-dihydro-indol-1-yl)ethanone

Step D: Preparation of 3,3-dimethyl-6-nitroindoline

Step E: Preparation of 3,3-dimethyl-1-(4-methyl-piperazin-1-yl)-6-nitro-2,3-dihydro-1H-indole

Step F Preparation of 3,3-dimethyl-1-(1-methyl(4-piperidyl))indoline-6-ylamine

Step G Preparation of N-[3,3-dimethyl-1-(1-methyl(4-piperidyl))indolin-6-yl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 49

[1407]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[3-(1-methyl(4-piperidyl))indol-5-yl]carboxamide

Step A: Preparation of 3-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl)-5-nitro-1H-indole

Step B: Preparation of 3-(1-methyl-4-piperidyl)indole-5-ylamine

Step C: Preparation of [2-(1H-indazol-6-ylamino)(3-pyridyl)]-N-[3-(1-methyl(4-piperidyl))indol-5-yl]carboxamide

EXAMPLE 50

[1411]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[4-(trifluoromethyl)phenyl]carboxamide

EXAMPLE 51

[1413]

N-{3-[3-(Dimethylamino)propyl]-5-(trifluoromethyl)phenyl)[2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

Step A: Preparation of {3-[3-amino-5-(trifluoromethyl)phenyl]propynyl}dimethylamine

Step B: Preparation of {3-[3-amino-5-(trifluoromethyl)phenyl]propyl}dimethylamine

Step C: Preparation of N-{3-[3-(Dimethylamino)propyl]-5-(trifluoromethyl)phenyl}[2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 52

[1417]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[5-(1-methyl(4-1,2,5,6-tetrahydropyridyl))-3-(trifluoromethyl)phenyl]carboxamide

Step A: Preparation of 4,4,5,5-tetramethyl-2-(1-methyl(4-1,2,5,6-tetrahydropyridyl))-1,3,2-dioxaborolane

Step B: Preparation of 5-(1-methyl(4-1,2,5,6-tetrahydropyridyl))-3-(trifluoro-methyl)phenylamine

Step C: Preparation of [2-(1H-indazol-6-ylamino)(3-pyridyl)]-N-[5-(1-methyl(4-1,2,5,6-tetrahydropyridyl))-3-(trifluoromethyl)phenyl]carboxamide

EXAMPLE 53

[1421]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[4-(1-methyl(4-piperidyl))phenyl]carboxamide

Step A: Preparation of 4-phenylpiperidine

Step B: Preparation of 1-methyl-4-phenylpiperidine

Step C: Preparation of 4-(1-methyl-4-piperidyl)phenylamine

Step D: Preparation of [2-(1H-indazol-6-ylamino)(3-pyridyl)]-N-[4-(1-methyl(4-piperidyl))phenyl]carboxamide

EXAMPLE 54

[1426]

N-[4-(tert-Butyl)-3-(3-piperidylpropyl)phenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

Step A: Preparation of 1-piperidylprop-2-en-1-one

Step B: Preparation of 1-(tert-butyl)-2-bromo-4-nitrobenzene

Step C: Preparation of (2E)-3-[2-(tert-butyl)-5-nitrophenyl]-1-piperidylprop-2-en-1-one

Step D: Preparation of 3-(5-amino-2-tert-butylphenyl)-1-piperidin-1-yl-propenone

Step E: Preparation of 4-(tert-butyl)-3-(3-piperidylpropyl)phenylamine

Step F: Preparation of N-[4-(tert-butyl)-3-(3-piperidylpropyl)phenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 55

[1434]

N-[3-((1E)-4-Pyrrolidinylbut-1-enyl)-4-(tert-butyl)phenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 56

[1436]

N-[4-(tert-Butyl)-3-(3-pyrrolidinylpropyl)phenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 57

[1438]

N-[4-(tert-Butyl)-3-(3-morpholin-4-ylpropyl)phenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 58

[1440]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-{3-[3-(4-methylpiperazinyl)-3-oxopropyl]phenyl}carboxamide

Step A: Preparation of 3-(3-nitrophenyl)-1-(4-methylpiperazinyl)propan-1-one

Step B: Preparation of 3-(3-aminophenyl)-1-(4-methylpiperazinyl)propan-1-one

Step C: Preparation of [2-(1H-indazol-6-ylamino)(3-pyridyl)]-N-{3-[3-(4-methylpiperazinyl)-3-oxopropyl]phenyl}carboxamide

EXAMPLE 59

[1444]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-{4-[3-(4-methylpiperazinyl)-3-oxopropyl]phenyl}carboxamide

EXAMPLE 60

[1446]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-{3-[3-(4-methylpiperazinyl)propyl]phenyl}carboxamide

EXAMPLE 61

[1448]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-{4-[3-(4-methylpiperazinyl)propyl]phenyl}carboxamide

EXAMPLE 62

[1450]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[1-(2-morpholin-4-ylethyl)indol-6-yl]carboxamide

Step A: Preparation of 1-(2-morpholin-4-ylethyl)indol-6-ylamine

Step B: Preparation of [2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-[1-(2-morpholin-4-ylethyl)indol-6-yl]carboxamide

EXAMPLE 63

[1453]

N-[4-(1,1-Dimethyl-3-morpholin-4-ylpropyl)phenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

Step A: Preparation of methyl 2-methyl-2-(4-nitrophenyl)propanoate

Step B: Preparation of 3-methyl-3-(4-nitrophenyl)butan-1-one

Step C: Preparation of 4-(1,1-dimethyl-3-morpholin-4-ylpropyl)phenylamine

Step D: Preparation of N-[4-(1,1-dimethyl-3-morpholin-4-ylpropyl)phenyl][2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 64

[1458]

2-(1H-Indazol-6-ylamino)-N-(4-{2,2,2-trifluoro-1-[2-(2-methoxy-ethoxy)-ethoxy]-1-trifluoromethyl-ethyl}-phenyl)-nicotinamide

Step A: Preparation of 4-{2,2,2-trifluoro-1-[2-(2-methoxy)ethoxy]-1-(trifluoromethyl)ethyl}phenylamine

Step B: Preparation of 2-fluoropyridine-3-carbonyl chloride

Step C: Preparation of [2-(1H-indazol-6-ylamino)(3-pyridyl)]-N-(4-{2,2,2-trifluoro-1-[2-(2-methoxyethoxy)ethoxy}-1-(trifluoromethyl)ethyl}phenyl)carboxamide

EXAMPLE 65

[1462]

[2-(1H-Indazol-6-ylamino)(3-pyridyl)]-N-{4-[2,2,2-trifluoro-1-(2-piperidylethoxy)-1-(trifluoromethyl)ethyl]phenyl}carboxamide

EXAMPLE 66

[1464]

N-[4-(tert-Butyl)phenyl][6-fluoro-2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

Step A: Preparation of (2,6-difluoro(3-pyridyl))-N-[4-(tert-butyl)phenyl]-carboxamide

Step B: Preparation of N-[4-(tert-butyl)phenyl][6-fluoro-2-(1H-indazol-6-ylamino)(3-pyridyl)]carboxamide

EXAMPLE 67

[1467]

[6-Fluoro-2-(1H-indazol-6-ylamino)(3-pyridyl)]-N-[4-(methylethyl)phenyl]carboxamide

EXAMPLE 68

[1469]

[6-Fluoro-2-(1H-indazol-6-ylamino)(3-pyridyl)]-N-[3-(trifluoromethyl)phenyl]carboxamide

EXAMPLE 69

[1471]

{2-[(1-(2-Pyridyl)pyrrolidin-3-yl)amino](3-pyridyl)}-N-[3-(trifluoromethyl)phenyl]carboxamide

Step A: Preparation of 1-(2-pyridyl)pyrrolidine-3-ylamine

Step B: Preparation of {2-[(1-(2-pyridyl)pyrrolidin-3-yl)amino](3-pyridyl)}-N-[3-(trifluoromethyl)phenyl]-carboxamide

EXAMPLE 70

[1474]

2-(1H-Indazol-6-ylamino)-N-[3-(3-morpholin-4-yl-propyl)-5-trifluoromethyl-phenyl]-nicotinamide

EXAMPLE 71

[1477]

2-(1H-Indazol-6-ylamino)-N-[3-(3-piperidin-1-yl-propyl)-5-trifluoromethyl-phenyl]-nicotinamide

EXAMPLE 72

[1479]

2-(1H-Indazol-6-ylamino)-N-[3-(1-methyl-piperidin-4-ylmethyl)-5-trifluoromethyl-phenyl]-nicotinamide

EXAMPLE 73

[1481]

2-(1H-Indazol-6-ylamino)-N-[3-(1-methyl-pyrrolidin-2-ylmethoxy)-5-trifluoromethyl-phenyl]-nicotinamide

EXAMPLE 74

[1482]

2-(1H-Indazol-6-ylamino)-N-[3-(piperidin-4-yloxy)-5-trifluoromethyl-phenyl]-nicotinamide

EXAMPLE 75

[1484]

2-(1H-Indazol-6-ylamino)-N-[3-(piperidin-4-ylmethoxy)-5-trifluoromethyl-phenyl]-nicotinamide

EXAMPLE 76

[1486]

N-(3,3-Dimethyl-1,1-dioxo-2,3-dihydro-1H-116-benzo[d]isothiazol-6-yl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 77

[1488]

2-(1H-Indazol-6-ylamino)-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-nicotinamide

EXAMPLE 78

[1490]

2-(1H-Indazol-6-ylamino)-N-[3-(1-methyl-piperidin-4-ylmethoxy)-4-pentafluoroethyl-phenyl]-nicotinamide

EXAMPLE 79

[1492]

2-(1H-Indazol-6-ylamino)-N-[3-(1-isopropyl-piperidin-4-ylmethoxy)-4-pentafluoroethyl-phenyl]-nicotinamide

EXAMPLE 80

[1494]

N-[3-(2-Hydroxy-3-pyrrolidin-1-yl-propoxy)-4-pentafluoroethyl-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 81

[1496]

2-(1H-Indazol-6-ylamino)-N-[4-pentafluoroethyl-3-(2-piperidin-1-yl-ethoxy)-phenyl]-nicotinamide

EXAMPLE 82

[1498]

N-[3-(2-Hydroxy-3-pyrrolidin-1-yl-propoxy)-4-pentafluoroethyl-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 83

[1500]

2-(1H-Indazol-6-ylamino)-N-[4-pentafluoroethyl-3-(2S-pyrrolidin-2-ylmethoxy)-phenyl]-nicotinamide

EXAMPLE 84

[1502]

2-(1H-Indazol-6-ylamino)-N-[4-pentafluoroethyl-3-(2R-pyrrolidin-2-ylmethoxy)-phenyl]-nicotinamide

EXAMPLE 85

[1504]

2-(1H-Indazol-6-ylamino)-N-[3-(pyrrolidin-2-ylmethoxy)-4-trifluoromethyl-phenyl]-nicotinamide

EXAMPLE 86

[1506]

2-(1H-Indazol-6-ylamino)-N-[3-(2-pyrrolidin-1-yl-ethoxy)-4-trifluoromethyl-phenyl]-nicotinamide

EXAMPLE 87

[1508]

N-(1-Acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 88

[1510]

2-(1H-Indazol-6-ylamino)-N-{4-[1-methyl-1-(1-methyl-piperidin-4-yl)-ethyl]-phenyl}-nicotinamide

EXAMPLE 89

[1512]

N-(4-Acetyl-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 90

[1514]

2-(1H-Indazol-6-ylamino)-N-[3-(1-methyl-piperidin-4-yl)-5-trifluoromethyl-phenyl]-nicotinamide

EXAMPLE 91

[1516]

N-(3-Bromo-5-trifluoromethyl-phenyl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 92

[1518]

2-(1H-Indazol-6-ylamino)-N-(2,2,4-trimethyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-nicotinamide

EXAMPLE 93

[1520]

N-[4-tert-Butyl-3-(piperidin-4-ylmethoxy)-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 94

[1522]

N-(2-Acetyl-4,4-dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 95

[1524]

1-Boc-2-(2-tert-Butyl-5-{[2-(1H-indazol-6-ylamino)-pyridine-3-carbonyl]-amino}-phenoxymethyl)-pyrrolidine

EXAMPLE 96

[1526]

N-[4-tert-Butyl-3-(pyrrolidin-2-ylmethoxy)-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 97

[1528]

2-(1H-Indazol-6-ylamino)-N-[3-(2S-pyrrolidin-2-ylmethoxy)-5-trifluoromethyl-phenyl]-nicotinamide

EXAMPLE 98

[1530]

N-(4-tert-Butyl-3-piperazin-1-yl-phenyl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 99

[1532]

N-(3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 100

[1534]

N-(3,3-Dimethyl-1-piperidin-4-yl-2,3-dihydro-1H-indol-6-yl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 101

[1536]

N-(2,2-Dimethyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 102

[1538]

N-[4-tert-Butyl-3-(4-propyl-piperazin-1-yl)-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 103

[1540]

N-[4-tert-Butyl-3-(4-isopropyl-piperazin-1-yl)-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 104

[1542]

2-(1H-Indazol-6-ylamino)-N-[3-(1-methylpyrrolidin-2-ylmethoxy)-5-trifluoromethyl-phenyl]-nicotinamide

EXAMPLE 105

[1544]

N-(4,4-Dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 106

[1546]

N-(3,3-Dimethyl-2,3-dihydro-benzofuran-6-yl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 107

[1548]

N-[1-(2-Dimethylamino-acetyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 108

[1550]

2-(1H-Indazol-6-ylamino)-N-[3-(4-methyl-piperazin-1-ylmethyl)-4-pentafluoroethyl-phenyl]-nicotinamide

EXAMPLE 109

[1552]

2-(1H-Indazol-6-ylamino)-N-[3-(4-Boc-piperazin-1-ylmethyl)-4-pentafluoroethyl-phenyl]-nicotinamide

EXAMPLE 110

[1554]

2-(1H-Indazol-6-ylamino)-N-(3-morpholin-4-ylmethyl-4-pentafluoroethyl-phenyl)-nicotinamide

EXAMPLE 111

[1556]

2-(1H-Indazol-6-ylamino)-N-(4-pentafluoroethyl-3-piperazin-1-ylmethyl-phenyl)-nicotinamide

EXAMPLE 112

[1558]

N-[4-tert-Butyl-3-(4-Boc-piperazin-1-yl)-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 113

[1560]

N-(4-tert-Butyl-3-nitro-phenyl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 114

[1562]

N-(3-Amino-4-tert-butyl-phenyl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 115

[1564]

N-[4-tert-Butyl-3-(2-hydroxy-ethylamino)-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 116

[1566]

N-[4-tert-Butyl-3-(2-morpholin-4-yl-ethylamino)-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

Step A: N-[3-(2-Bromo-ethylamino)-4-tert-butyl-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

Step B: N-[4-tert-Butyl-3-(2-morpholin-4-yl-ethylamino)-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 117

[1569]

N-[4-tert-Butyl-3-(1-Boc-piperidin-4-ylamino)-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 118

[1571]

2-(1H-Indazol-6-ylamino)-N-[2-(2-morpholin-4-yl-ethyl)-1,2,3,4-tetrahydro-isoquinolin-7-yl]-nicotinamide

EXAMPLE 119

[1573]

N-[4-tert-Butyl-2-(4-methyl-piperazin-1-yl)-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 120

[1575]

2-(1H-Indazol-6-ylamino)-N-(2-oxo-4-trifluoromethyl-2H-chromen-7-yl)-nicotinamide

EXAMPLE 121

[1577]

2-(1H-Indazol-6-ylamino)-N-[3-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl)-5-trifluoromethyl-phenyl]-nicotinamide

EXAMPLE 122

[1579]

2-(1H-Indazol-6-ylamino)-N-(1H-indol-7-yl)-nicotinamide

EXAMPLE 123

[1581]

2-(1H-Indazol-6-ylamino)-N-(4-pentafluoroethyl-phenyl)-nicotinamide

EXAMPLE 124

[1583]

N-[4-tert-Butyl-3-(piperidin-4-ylamino)-phenyl]-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 125

[1585]

2-(1H-Indazol-6-ylamino)-N-(3-piperazin-1-ylmethyl-5-trifluoromethyl-phenyl)-nicotinamide

EXAMPLE 126

[1587]

N-(4,4-Dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 127

[1589]

N-(1-Boc-4,4-Dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-(1H-indazol-6-ylamino)-nicotinamide

EXAMPLE 128

[1591]

2-(1H-Indazol-6-ylamino)-N-[3-(4-Boc-piperazin-1-ylmethyl)-5-trifluoromethyl-phenyl]-nicotinamide

EXAMPLE 129

[1593]

N-[3-(1-Methyl-pyrrolidin-2-ylmethoxy)-5-trifluoromethyl-phenyl]-2-(4-oxazol-5-yl-phenylamino)-nicotinamide

[1596]

TABLE 1
#	R1	R2
130.	2-chlorophenyl	H
131.	4-benzimidazolyl	H
132.	5-benzimidazolyl	H
133.	7-benzimidazolyl	H
134.	2-chlorophenyl	5-F
135.	3-isoquinolinyl	5-F
136.	2-quinolinyl	5-F
137.	2-benzthiazolyl	5-F
138.	2-benzimidazolyl	5-F
139.	4-benzimidazolyl	5-F
140.	5-benzimidazolyl	5-F
141.	6-benzimidazolyl	5-F
142.	7-benzimidazolyl	5-F
143.	4-chlorophenyl	3-pyridyl
144.	4-pyridyl	H
145.	4-pyridyl	6-CH3
146.	4-chlorophenyl-	5-Cl
147.	3,4-dichlorophenyl-	5-F
148.	4-fluorophenyl	6-CH3
149.	3-chlorophenyl	6-F
150.	3-fluorophenyl	6-F
151.	3-fluoro-4-methoxyphenyl	6-CH3
152.	3-fluoro-4-methylphenyl	6-Cl
153.	4-phenoxyphenyl	H
154.	3-phenoxyphenyl	H
155.	4-biphenyl	H
156.	4-cyclohexylphenyl	H
157.	2-quinolyl	H
158.	3-isoquinolyl	H
159.	3-quinolyl	H
160.	1-isoquinolyl	H
161.	5-quinolyl	H
162.	5-isoquinolyl	H
163.	6-quinolyl	H
164.	6-isoquinolyl	H
165.	7-quinolyl	H
166.	7-isoquinolyl	H
167.	4-quinolyl	H
168.	4-isoquinolyl	H
169.	4-pyridyl	H
170.	4-pyrimidinyl	H
171.	2-pyrimidinyl	H
172.	6-pyrimidinyl	H
173.	4-pyridazinyl	H
174.	5-pyridazinyl	H
175.	4-indolyl	H
176.	5-isoindolyl	H
177.	5-naphthyridinyl	H
178.	6-quinozalinyl	H
179.	6-isoquinolyl	H
180.	4-naphthyridinyl	H
181.	5-quinozalinyl	H
182.	4-naphthyridinyl	H
183.	7-tetrahydroquinolinyl	H
184.	6-indazolyl	H
185.	6-isoindolyl	H
186.	5-indazolyl	H
187.	5-isoindolyl	H
188.	6-benzothienyl	H
189.	6-benzofuryl	H
190.	5-benzothienyl	H
191.	5-benzofuryl	H
192.	2-benzimidazolyl	H
193.	2-benzoxazolyl	H
194.	2-benzthiazolyl	H
195.	6-benzimidazolyl	H
196.	6-benzoxazolyl	H
197.	6-benzthiazolyl	H
198.	2-quinazolinyl	H
199.	3-(phenoxy)-6-pyridyl	H
200.	4-(phenylcarbonyl)phenyl	H
201.	4-(phenylamino)phenyl	H
202.	4-cyclohexyloxyphenyl	H
203.	4-(3-thienyl)phenyl	H
204.	4-(pyrazol-3-yl)phenyl	H
205.	4-chlorophenyl	6-Cl
206.	4-pyridyl	6-Cl
207.	3-methoxyphenyl	6-Cl
208.	4-hydroxyphenyl	6-Cl
209.	3-hydroxyphenyl	H
210.	2-hydroxyphenyl	H
211.	4-chlorophenyl	6-phenyl
212.	4-phenoxyphenyl	6-F
213.	4-biphenyl	6-phenyl
214.	4-hydroxyphenyl	6-phenyl
215.	4-cyclohexylphenyl	6-F
216.	3-isoquinolyl	6-phenyl
217.	4-piperidinylmethylphenyl	H
218.	4-morpholinylmethylphenyl	H

[1597]

TABLE 2a
#	R1
219.	4-chlorophenyl
220.	3,4-dichlorophenyl
221.	4-phenoxyphenyl
222.	4-biphenyl
223.	4-cyclohexylphenyl
224.	3-isoquinolyl

[1598]

TABLE 2b
#	R1
225.	4-chlorophenyl
226.	3,4-dichlorophenyl
227.	4-phenoxyphenyl
228.	4-biphenyl
229.	4-cyclohexylphenyl
230.	3-isoquinolyl

[1599]

TABLE 2c
#	R1	A5
231.	4-chlorophenyl	NH
232.	3,4-dichlorophenyl	NH
233.	4-phenoxyphenyl	NH
234.	4-biphenyl	NH
235.	4-cyclohexylphenyl	NH
236.	3-isoquinolyl	NH
237.	4-chlorophenyl	O
238.	3,4-dichlorophenyl	O
239.	4-phenoxyphenyl	O
240.	4-biphenyl	O
241.	4-cyclohexylphenyl	O
242.	3-isoquinolyl	O
243.	3,4-dichlorophenyl	S
244.	4-phenoxyphenyl	S
245.	4-biphenyl	S
246.	4-cyclohexylphenyl	S
247.	3-isoquinolyl	S

[1600]

TABLE 2d
#	R1	A5
248.	4-chlorophenyl	NH
249.	3,4-dichlorophenyl	NH
250.	4-phenoxyphenyl	NH
251.	4-biphenyl	NH
252.	4-cyclohexylphenyl	NH
253.	3-isoquinolyl	NH
254.	4-chlorophenyl	O
255.	3,4-dichlorophenyl	O
256.	4-phenoxyphenyl	O
257.	4-biphenyl	O
258.	4-cyclohexylphenyl	O
259.	3-isoquinolyl	O
260.	3,4-dichlorophenyl	S
261.	4-phenoxyphenyl	S
262.	4-biphenyl	S
263.	4-cyclohexylphenyl	S
264.	3-isoquinolyl	S

[1601]

TABLE 2e
#	R1	A5
265.	4-chlorophenyl	NH
266.	3,4-dichlorophenyl	NH
267.	4-phenoxyphenyl	NH
268.	4-biphenyl	NH
269.	4-cyclohexylphenyl	NH
270.	3-isoquinolyl	NH
271.	4-chlorophenyl	O
272.	3,4-dichlorophenyl	O
273.	4-phenoxyphenyl	O
274.	4-biphenyl	O
275.	4-cyclohexylphenyl	O
276.	3-isoquinolyl	O
277.	3,4-dichlorophenyl	S
278.	4-phenoxyphenyl	S
279.	4-biphenyl	S
280.	4-cyclohexylphenyl	S
281.	3-isoquinolyl	S

[1602]

TABLE 2f
#	R1	A5
282.	4-chlorophenyl	NH
283.	3,4-dichlorophenyl	NH
284.	4-phenoxyphenyl	NH
285.	4-biphenyl	NH
286.	4-cyclohexylphenyl	NH
287.	3-isoquinolyl	NH
288.	4-chlorophenyl	O
289.	3,4-dichlorophenyl	O
290.	4-phenoxyphenyl	O
291.	4-biphenyl	O
292.	4-cyclohexylphenyl	O
293.	3-isoquinolyl	O
294.	3,4-dichlorophenyl	S
295.	4-phenoxyphenyl	S
296.	4-biphenyl	S
297.	4-cyclohexylphenyl	S
298.	3-isoquinolyl	S

[1603]

TABLE 2g
#	R1	A5
299.	4-chlorophenyl	NH
300.	3,4-dichlorophenyl	NH
301.	4-phenoxyphenyl	NH
302.	4-biphenyl	NH
303.	4-cyclohexylphenyl	NH
304.	3-isoquinolyl	NH
305.	4-chlorophenyl	O
306.	3,4-dichlorophenyl	O
307.	4-phenoxyphenyl	O
308.	4-biphenyl	O
309.	4-cyclohexylphenyl	O
310.	3-isoquinolyl	O

[1604]

TABLE 2h
#	R1	A5
311.	4-chlorophenyl	NCH3
312.	3,4-dichlorophenyl	NCH3
313.	4-phenoxyphenyl	NH
314.	4-biphenyl	NH
315.	4-cyclohexylphenyl	NH
316.	4-tertbutylphenyl	NCH3
317.	4-chlorophenyl	O
318.	3,4-dichlorophenyl	O
319.	4-phenoxyphenyl	O
320.	4-biphenyl	O
321.	4-cyclohexylphenyl	O
322.	3-isoquinolyl	O