Patent ID: 6399609
Filing Date: 2002-06-04
Classification: A61P,C07D

Abstract:
A method of treating an affective disorder, anxiety, depression, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal disease, anorexia nervosa or other feeding disorder, drug or alcohol withdrawal symptoms, drug addiction, or inflammatory disorder in a mammal comprising administering to the mammal a therapeutically effective amount of a CRF antagonist compound of formula I: or a pharmaceutically accetable salt or prodrug thereof, wherein:A is N or Câ€”R11; X is H, OR1, S(O)nR1, NR1R2, CR1R2R3, phenyl (optionally substituted with 1-4 groups independently chosen from halogen, C1-C4 haloalkyl, nitro, C1-C4 alkyl, C2-C5 carboalkoxy, cyano, OH, C1-C4 alkoxy, SH, C1-C4 alkylthio, NH2, C1-C4 alkylamino, C2-C8 dialkylamino, or phenyl) or heteroaryl (optionally substituted at one to all valence-allowed positions with groups independently chosen from halogen, C1-C4 haloalkyl, nitro, C1-C4 alkyl, C2-C5 carboalkoxy, cyano, OH, C1-C4 alkoxy, SH, C1-C4 alkylthio, NH2, C1-C4 alkylamino, C2-C8 dialkylamino, or phenyl); n is 0, 1 or 2; R1 is C1-C12 alkyl, C2-C12 alkoxyalkyl, C3-C12 cycloalkyl, C4-C12 cycloalkylalkyl, C2-C12 alkenyl, C2-C12 alkynyl, aryl-(C1-C12 alkyl), C3-C12 dialkylaminoalkyl, C2-C13 cyanoalkyl, C2-C5 carboalkoxy-(C1-C12 alkyl), phenyl (optionally substituted with 1-4 groups independently chosen from halogen, C1-C4 haloalkyl, nitro, C1-C4 alkyl, C2-C5 carboalkoxy, cyano, OH, C1-C4 alkoxy, SH, C1-C4 alkylthio, NH2, C1-C4 alkylamino, C2-C8 dialkylamino, or phenyl), or heteroaryl (optionally substituted at one to all valence-allowed positions with groups independently chosen from halogen, C1-C4 haloalkyl, nitro, C1-C4 alkyl, C2-C5 carboalkoxy, cyano, OH, C1-C4 alkoxy, SH, C1-C4 alkylthio, NH2, C1-C4 alkylamino, C2-C8 dialkylamino, or phenyl); R2 and R3 are independently chosen from H, C1-C12 alkyl, C2-C12 alkoxyalkyl, C3-C12 cycloalkyl, C4-C12 cycloalkylalkyl, C2-C12 alkenyl, C2-C12 alkynyl, aryl-(C1-C12 alkyl), C3-C12 dialkylaminoalkyl, C2-C13 cyanoalkyl, C1-C4 carboalkoxy, C2-C12 carboalkoxyalkyl, C(&boxH;O) CH3, phenyl (optionally substituted with 1-4 groups independently chosen from halogen, C1-C4 haloalkyl, nitro, C1-C4 alkyl, C2-C5 carboalkoxy, cyano, OH, C1-C4 alkoxy, SH, C1-C4 alkylthio, NH2, C1-C4 alkylamino, C2-C8 dialkylamino, or phenyl), or heteroaryl (optionally substituted at one to all valence-allowed positions with groups independently chosen from halogen, C1-C4 haloalkyl, nitro, C1-C4 alkyl, C2-C5 carboalkoxy, cyano, OH, C1-C4 alkoxy, SH, C1-C4 alkylthio, NH2, C1-C4 alkylamino, C2-C8 dialkylamino, or phenyl); R4 is H, C1-C12 alkyl, allyl, propargyl or benzyl (optionally substituted with 1-4 groups independently chosen from halogen, C1-C4 haloalkyl, nitro, C1-C4 alkyl, C2-C5 carboalkoxy, cyano, OH, C1-C4 alkoxy, SH, C1-C4 alkylthio, NH2, C1-C4 alkylamino, C2-C8 dialkylamino, or phenyl); R1 and R4 may also optionally be taken together, along with the other four interconnected atoms, to form a ring of 5-9 total atoms, the structural sequence between the X group and the ring nitrogen atom consisting of the group (CH2)pW(CH2)q; p and q are independently 0, 1 or 2; W is CH2, C(CH3)2, C(&boxH;O), O, S or NCH3; R5, R6, R7 and R8 are independently chosen from H, C1-C4 alkyl, allyl, propargyl, phenyl (optionally substituted with 1-4 groups independently chosen from halogen, C1-C4 haloalkyl, nitro, C1-C4 alkyl, C2-C5 carboalkoxy, cyano, OH, C1-C4 alkoxy, SH, C1-C4 alkylthio, NH2, C1-C4 alkylamino, C2-C8 dialkylamino, or phenyl) or benzyl (optionally substituted with 1-4 groups independently chosen from halogen, C1-C4 haloalkyl, nitro, C1-C4 alkyl, C2-C5 carboalkoxy, cyano, OH, C1-C4 alkoxy, SH, C1-C4 alkylthio, NH2, C1-C4 alkylamino, C2-C8 dialkylamino, or phenyl); R4, R5 and R6 may also be taken together, along with the two interconnecting atoms, to constitute either an imidazole or tetrazole ring, the imidazole ring being optionally substituted with 1-2 groups chosen independently from C1-C4 alkyl or phenyl; R5 and R6 may also be taken together to be O, S or NR12; R9 is phenyl (optionally substituted with 1-4 groups chosen from halogen, C1-C4 haloalkyl, C1-C4 alkyl, C2-C6 alkenyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl, C2-C6 dialkylamino, nitro, C2-C5 carboalkoxy or cyano), pyridyl (optionally substituted with 1-4 groups chosen from halogen, C1-C4 haloalkyl, C1-C4 alkyl, C2-C6 alkenyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl, C2-C6 dialkylamino, nitro, C2-C5 carboalkoxy or cyano), or pyrimidyl (optionally substituted with 1-4 groups chosen from halogen, C1-C4 haloalkyl, C1-C4 alkyl, C2-C6 alkenyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl, C2-C6 dialkylamino, nitro, C2-C5 carboalkoxy or cyano); R10 is H, C1-C4 alkyl or cyano; R11 is H, C1-C4 alkyl or halogen; R12 is H, C1-C4 alkyl or phenyl; aryl is phenyl, biphenyl or naphthyl; and heteroaryl is pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl or pyrazolyl.