Patent ID: 6448261
Filing Date: 2002-09-10
Classification: A61P,C07D

Abstract:
A CRF antagonist compound of formula I: or a pharmaceutically acceptable salt form thereof, wherein:Y is N or CR2; Z is NR3, O, or S(O)n; Ar is naphthyl, pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl or pyrazolyl, each optionally substituted with 1 to 5 R5 groups; R1 is independently at each occurrence H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, halo, CN, C1-C4 haloalkyl, â€”NR9R10, NR9COR10, â€”OR11, SH or â€”S(O)nR12; R2 is H, C1-C4 alkyl, C1-C6 cycloalkyl, halo, CN, â€”NR6R7, NR9COR10, C1-C4 haloalkyl, â€”OR7, SH or â€”S(O)nR12; R3 is H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl or C4-C12 cycloalkylalkyl each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, â€”OR7, SH, â€”S(O)nR13, â€”COR7, â€”CO2R7, â€”OC(O)R13, â€”NR8COR7, â€”N(COR7)2, â€”NR8CONR6R7, â€”NR8CO2R13, â€”NR6R7, â€”CONR6R7, aryl, heteroaryl and heterocyclyl, where the aryl, heteroaryl or heterocyclyl is optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, â€”OR7, SH, â€”S(O)nR13, â€”COR7, â€”CO2R7, â€”OC(O)R13, â€”NR8COR7, â€”N(COR7)2, â€”NR8CONR6R7, â€”NR8CO2R13, â€”NR6R7, and â€”CONR6R7; R4 is H, C1-C4 alkyl, allyl, or propargyl, where C1-C4 alkyl, allyl, or propargyl is optionally substituted with C3-C6 cycloalkyl and where C1-C4 alkyl is optionally substituted with, â€”OR7, â€”S(O)nR12 or â€”CO2R7; R5 is independently at each occurrence C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, â€”NO2, halo, â€”CN, C1-C4 haloalkyl, â€”NR6R7, NR8COR7, NR8CO2R7, â€”COR7 â€”OR7, â€”CONR6R7, â€”CO(NOR9)R7, CO2R7, or â€”S(O)nR7, where C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-C12 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, â€”NO2, halo, â€”CN, â€”NR6R7, â€”NR6R7, NR8COR7, NR8CO2R7, â€”COR7 â€”OR7, â€”CONR6R7, CO2R7, â€”CO(NOR9)R7, or â€”S(O)nR7; R6 and R7 are independently at each occurrence H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, aryl, aryl(C1-C4 alkyl)-, heteroaryl or heteroaryl(C1-C4 alkyl)-; or NR6R7 is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine; R8 is independently at each occurrence H or C1-C4 alkyl; R9 and R10 are independently at each occurrence selected from H, C1-C4 alkyl, or C3-C6 cycloalkyl; R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, or C3-C6 cycloalkyl; R12 is C1-C4 alkyl or C1-C4 haloalkyl; R13 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, aryl, aryl(C1-C4 alkyl)-, heteroaryl or heteroaryl(C1-C4 alkyl)-; aryl is phenyl or naphthyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, â€”OR7, SH, â€”S(O)nR13, â€”COR7, â€”CO2R7, â€”OC(O)R13, â€”NR8COR7, â€”N(COR7)2, â€”NR8CONR6R7, â€”NR8CO2R13, â€”NR6R7, and â€”CONR6R7; heteroaryl is pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, or indazolyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, â€”OR7, SH, â€”S(O)nR13, â€”COR7, â€”CO2R7, â€”OC(O)R13, â€”NR8COR7, â€”N(COR7)2, â€”NR8CONR6R7, â€”NR8CO2R13, â€”NR6R7, and â€”CONR6R7; heterocyclyl is saturated or partially saturated heteroaryl, optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, â€”OR7, SH, â€”S(O)nR13, â€”COR7, â€”CO2R7, â€”OC(O)R13, â€”NR8COR7, â€”N(COR7)2, â€”NR8CONR6R7, â€”NR8CO2R13, â€”NR6R7, and â€”CONR6R7; and n is independently at each occurrence 0, 1 or 2.