| 主权项 |
1. A compound of formula (I): including any stereochemically isomeric form thereof, wherein m is 0, 1 or 2 and when m is 0 then a direct bond is intended; n is 0, 1, 2 or 3 and when n is 0 then a direct bond is intended; p is 0 or 1 and when p is 0 then a direct bond is intended; s is 0 or 1 and when s is 0 then a direct bond is intended; t is 0 or 1 and when t is 0 then a direct bond is intended; X is C(═O) or CHR8, wherein
R8 is selected from hydrogen; C1-6alkyl; C3-7cycloalkyl; —C(═O)—NR17R18; carboxyl; arylC1-6alkyloxycarbonyl; heteroaryl; heteroarylcarbonyl; heteroarylC1-6alkyloxycarbonyl; piperazinylcarbonyl; pyrrolidinyl; piperidinylcarbonyl; C1-6alkyloxycarbonyl; C1-6alkyl substituted with a substituent selected from hydroxy, amino, aryl and heteroaryl; C3-7cycloalkyl substituted with a substituent selected from hydroxy, amino, aryl and heteroaryl; piperazinylcarbonyl substituted with a substituent selected from hydroxy, hydroxyC1-6alkyl and hydroxyC1-6alkyloxyC1-6alkyl; pyrrolidinyl substituted with hydroxyC1-6alkyl; and piperidinylcarbonyl substituted with one or two substituents selected from hydroxy, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkyl(dihydroxy)C1-6alkyl and C1-6alkyloxy(hydroxy)C1-6alkyl;R17 and R18 are each independently selected from hydrogen, C1-6alkyl, di(C1-6alkyl)aminoC1-6alkyl, arylC1-6alkyl, C1-6alkyloxyC1-6alkyl, hydroxyC1-6alkyl, hydroxyC1-6alkyl(C1-6alkyl), or hydroxyC1-6alkyl(arylC1-6alkyl);is —CR9═C< and then the dotted line is a bond, —C(═O)—CH<, —C(═O)—N<, —CHR9—CH<, or —CHR9—N<, wherein each R9 is independently hydrogen or C1-6alkyl, or wherein R9 together with one of R2 or R20 form a direct bond;
R1 is hydrogen; aryl; heteroaryl; C1-6alkyloxycarbonyl; C1-12alkyl; or C1-12alkyl substituted with one or two substituents independently selected from hydroxy, aryl, heteroaryl, amino, C1-6alkyloxy, mono- or di(C1-6alkyl)amino, morpholinyl, piperidinyl, pyrrolidinyl, piperazinyl, C1-6alkylpiperazinyl, arylC1-6alkylpiperazinyl, heteroarylC1-6alkylpiperazinyl, C3-7cycloalkyl-piperazinyl and C3-7cycloalkylC1-6alkylpiperazinyl; R2 and R20 are each independently selected from
halo, hydroxy, cyano, nitro, carboxyl;polyhaloC1-6alkyl, polyhaloC1-6alkyloxy;C1-6alkyl, C3-7cycloalkyl, C2-6alkenyl, aryl, heteroaryl, arylC1-6alkyl, heteroaryl-C1-6alkyl, C3-7cycloalkylC1-6alkyl, morpholinyl, piperidinyl, pyrrolidinyl, piperazinyl, C1-6alkyloxy, aryloxy, heteroaryloxy, C1-6alkylthio, arylthio, heteroarylthio,C1-6alkylcarbonyl,C3-7cycloalkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, C1-6alkyloxycarbonyl, C3-7cycloalkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, C1-6alkylcarbonyloxy, C3-7cycloalkylcarbonyloxy, arylcarbonyloxy or heteroarylcarbonyloxy, any of said groups being optionally and independently substituted with one or more, preferably one or two, substituents selected from halo, hydroxy, cyano, nitro, carboxyl, amino, mono- or di(C1-6alkyl)amino, C1-6alkyl, polyhaloC1-6alkyl, aryl, heteroaryl, C1-6alkyloxy, C1-6alkylcarbonyl,C1-6alkyloxycarbonyl andC1-6alkylcarbonyloxy; and—(CH2)w—(C(═O))yNR21R22 wherein
w is 0, 1, 2, 3, 4, 5 or 6 and when w is 0 then a direct bond is intended;y is 0 or 1 and when y is 0 then a direct bond is intended; andwherein in the case R2 or R20 is selected from the group consisting of C1-6alkyl and C1-6alkyloxy, R2 or R20 cannot be fluorine;R21 and R22 are each independently selected from hydrogen, C1-6alkyl, C3-7cycloalkyl, C1-6alkylcarbonyl and arylC1-6alkylcarbonyl, any of said groups being optionally and independently substituted with one or more, preferably one or two, substituents selected from halo, hydroxy, amino, mono- ordi(C1-6alkyl)amino, C1-6alkyl, polyhaloC1-6alkyl, C1-6alkyloxy, aryl and heteroaryl;or R21 and R22 together with the nitrogen to which they are attached form morpholinyl, piperidinyl, pyrrolidinyl or piperazinyl, any of said groups being optionally and independently substituted with one or more, preferably one or two, substituents selected from C1-6alkyl, polyhaloC1-6alkyl, C1-6alkyloxy,C3-7cycloalkyl, C3-7cycloalkylC1-6alkyl, arylC1-6alkyl and heteroarylC1-6alkyl; or R2 and R20 together with the phenyl ring to which they are attached form a naphthalenyl group, optionally substituted with one or more, preferably one or two, substituents each independently selected from halo, hydroxy, amino, mono- or di(C1-6alkyl)amino, C1-6alkyl, polyhaloC1-6alkyl, C1-6alkyloxy, aryl and heteroaryl; or R2 and R20 together form a bivalent radical of the formula —(CH2)b— wherein b is 3, 4 or 5, optionally substituted with one or more, preferably one or two, substituents selected from halo, hydroxy, amino, mono- or di(C1-6alkyl)amino, C1-6alkyl, polyhaloC1-6alkyl, C1-6alkyloxy, aryl and heteroaryl; or one of R2 or R20 is as defined above and the other one of R2 or R20 together with R9 form a direct bond; R3 is hydrogen; C1-6alkyl; heteroaryl; C3-7cycloalkyl; C1-6alkyl substituted with a substituent selected from hydroxy, amino, aryl and heteroaryl; or C3-7cycloalkyl substituted with a substituent selected from hydroxy, amino, aryl and heteroaryl; R4 and R5 are each independently hydrogen, halo, C1-6alkyl, hydroxyC1-6alkyl, polyhalo- C1-6alkyl, cyano, cyanoC1-6alkyl, hydroxy, amino, C2-6alkenyl or C1-6alkyloxy; or R4 and R5 together form a bivalent radical selected from methylenedioxy or ethylenedioxy; R6 is hydrogen, C1-6alkyloxycarbonyl, or C1-6alkyl; when p is 1 then R7 is hydrogen, arylC1-6alkyl, hydroxy, or heteroarylC1-6alkyl; Z is a radical selected from wherein
R10 or R11 are each independently selected from hydrogen, halo, hydroxy, amino,C1-6alkyl, nitro, polyhaloC1-6alkyl, cyano, cyanoC1-6alkyl, tetrazoloC1-6alkyl, aryl, heteroaryl, arylC1-6alkyl, heteroarylC1-6alkyl, aryl(hydroxy)C1-6alkyl, heteroaryl(hydroxy)C1-6alkyl, arylcarbonyl, heteroarylcarbonyl, C1-6alkylcarbonyl, arylC1-6alkylcarbonyl, heteroarylC1-6alkylcarbonyl, C1-6alkyloxy, C3-7cycloalkylcarbonyl, C3-7cycloalkyl(hydroxy)C1-6alkyl, arylC1-6alkyloxyC1-6alkyl,C1-6alkyloxyC1-6alkyloxyC1-6alkyl, C1-6alkylcarbonyloxyC1-6alkyl,C1-6alkyloxycarbonylC1-6alkyloxyC1-6alkyl, hydroxyC1-6alkyloxyC1-6alkyl,C1-6alkyloxycarbonylC2-6alkenyl, C1-6alkyloxyC1-6alkyl, C1-6alkyloxycarbonyl,C1-6alkylcarbonyloxy, aminocarbonyl, hydroxyC1-6alkyl, aminoC1-6alkyl, hydroxycarbonyl, hydroxycarbonylC1-6alkyl and —(CH2)v—(C(═O))r—(CHR19)u—NR13R14, wherein
v is 0, 1, 2, 3, 4, 5, or 6 and when v is 0 then a direct bond is intended;r is 0 or 1 and when r is 0 then a direct bond is intended;u is 0, 1, 2, 3, 4, 5, or 6 and when u is 0 then a direct bond is intended;R19 is hydrogen or C1-6alkyl;R13 and R14 are each independently selected from hydrogen; C1-12alkyl;C1-6alkylcarbonyl; C1-6alkylsulfonyl; arylC1-6alkylcarbonyl; C3-7cycloalkyl;C3-7cycloalkylcarbonyl; —(CH2)k—NR15R16; C1-12alkyl substituted with a substituent selected from hydroxy, hydroxycarbonyl, cyano,C1-6alkyloxycarbonyl, C1-6alkyloxy, aryl or heteroaryl; or C3-7cycloalkyl substituted with a substituent selected from hydroxy, C1-6alkyloxy, aryl, amino, arylC1-6alkyl, heteroaryl or heteroarylC1-6alkyl; orR13 and R14 together with the nitrogen to which they are attached form morpholinyl, piperidinyl, pyrrolidinyl, piperazinyl, or piperazinyl substituted with a substituent selected from C1-6alkyl, arylC1-6alkyl, arylC1-6alkyloxycarbonyl, heteroarylC1-6alkyl, C3-7cycloalkyl andC3-7cycloalkylC1-6alkyl; wherein
k is 0, 1, 2, 3, 4, 5, or 6 and when k is 0 then a direct bond is intended;R15 and R16 are each independently selected from hydrogen;C1-12alkyl; arylC1-6alkyloxycarbonyl; C3-7cycloalkyl; substituted with a substituent selected from hydroxy, C1-6alkyloxy, aryl, and heteroaryl; and C3-7cycloalkyl substituted with a substituent selected from hydroxy, C1-6alkyloxy, aryl, arylC1-6alkyl, heteroaryl, and heteroarylC1-6alkyl; orR15 and R16 together with the nitrogen to which they are attached form morpholinyl, piperazinyl, or piperazinyl substituted with C1-6alkyloxycarbonyl;R12 is hydrogen; C1-6alkyl; C3-7cycloalkyl; C1-6alkyl substituted with a substituent selected from hydroxy, amino, C1-6alkyloxy and aryl; or C3-7cycloalkyl substituted with a substituent selected from hydroxy, amino, aryl and C1-6alkyloxy;aryl is phenyl or naphthalenyl;
each phenyl or naphthalenyl can optionally be substituted with one, two or three substituents each independently selected from halo, hydroxy, C1-6alkyl, amino, polyhaloC1-6alkyl and C1-6alkyloxy; andeach phenyl or naphthalenyl can optionally be substituted with a bivalent radical selected from methylenedioxy and ethylenedioxy;heteroaryl is pyridinyl, indolyl, quinolinyl, imidazolyl, furanyl, thienyl, oxadiazolyl, tetrazolyl, benzofuranyl or tetrahydrofuranyl;
each pyridinyl, indolyl, quinolinyl, imidazolyl, furanyl, thienyl, oxadiazolyl, tetrazolyl, benzofuranyl, or tetrahydrofuranyl can optionally be substituted with one, two or three substituents each independently selected from halo, hydroxy, C1-6alkyl, amino, polyhaloC1-6alkyl, aryl, arylC1-6alkyl or C1-6alkyloxy; oreach pyridinyl, indolyl, quinolinyl, imidazolyl, furanyl, thienyl, benzofuranyl, or tetrahydrofuranyl can optionally be substituted with a bivalent radical selected from methylenedioxy or ethylenedioxy;an N-oxide form thereof or, an addition salt thereof. |
