Patent ID: 6962934
Filing Date: 2005-11-08
Classification: A61K,A61P,C07C,C07K

Abstract:
1. A compound of the formula I: or a pharmaceutically acceptable salt thereof, wherein R 1 is R′ 100 , R′ 100 represents aryl, heteroaryl, heterocyclyl, -aryl-W-aryl, -aryl-W-heteroaryl, -aryl-W-heterocyclyl, -heteroaryl-W-aryl, -heteroaryl-W-heteroaryl, -heteroaryl-W-heterocyclyl, -heterocyclyl-W-aryl, -heterocyclyl-W-heteroaryl, -heterocyclyl-W-heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from —OR, —NO W is —(CH 2 ) 0-4 —, —O—, —S(O) 0-2 —, —N(R 135 )—, —CR(OH)— or —C(O)—; R 102 and R 102 ′ independently are hydrogen, or C R 105 and R′ 105 independently represent —H, —R 110 , —R 120 , C 3 -C 7 cycloalkyl, —(C 1 -C 2 alkyl)-(C 3 -C 7 cycloalkyl), —(C 1 -C 6 alkyl)-O—(C 1 -C 3 alkyl), C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, or C 1 -C 6 alkyl chain with one double bond and one triple bond, or C C R 105 and R′ 105 together with the atom to which they are attached form a 3 to 7 membered carbocylic ring, where one member is optionally a heteratom selected from —O—, —S(O) 0-2 —, —N(R 135 )—, the ring being optionally substituted with 1, 2 or 3 independently selected R 140 groups; R 135 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, —(CH 2 ) 0-2 -(aryl), —(CH 2 ) 0-2 -(heteroaryl), or —(CH 2 ) 0-2 -(heterocyclyl); R 140 is heterocyclyl optionally substituted with 1, 2, 3, or 4 groups independently selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(C 1 -C 6 )alkylamino, di(C 1 -C 6 )alkylamino, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, amino(C 1 -C 6 )alkyl, mono(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, and ═O; R 150 is hydrogen, C 3 -C 7 cycloalkyl, —(C 1 -C 2 alkyl)-(C 3 -C 7 cycloalkyl), C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkyl with one double bond and one triple bond, —R 110 , —R 120 , or C R 150 ′ is C 3 -C 7 cycloalkyl, —(C 1 -C 3 alkyl)-(C 3 -C 7 cycloalkyl), C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkyl with one double bond and one triple bond, —R 110 , —R 120 , or C R 110 is aryl optionally substituted with 1 or 2 R 125 groups; R 125 at each occurrence is independently halogen, amino, mono- or dialkylamino, —OH, —C≡N, —SO 2 —NH 2 , —SO 2 —NH—C 1 -C 6 alkyl, —SO 2 —N(C 1 -C 6 alkyl) 2 , —SO 2 —(C 1 -C 4 alkyl), —CO—NH 2 , —CO—NH—C 1 -C 6 alkyl, or —CO—N(C 1 -C 6 alkyl) 2 , or C C R 120 is heteroaryl, which is optionally substituted with 1 or 2 R 125 groups; and R 130 is heterocyclyl optionally substituted with 1 or 2 R 125 groups; R 2 is C C —(CH aryl, heteroaryl, heterocyclyl, —C R 3 is H or is C C —(CH aryl, heteroaryl, heterocyclyl, —C R 4 is hydrogen, —(CR 245 R 250 ) 0-4 -aryl, —(CR 245 R 250 ) 0-4 -heteroaryl, —(CR 245 R 250 ) 0-4 -heterocyclyl, —(CR 245 R 250 ) 0-4 -aryl-heteroaryl, —(CR 245 R 250 ) 0-4 -aryl-heterocyclyl, —(CR 245 R 250 ) 0-4 -aryl-aryl, —(CR 245 R 250 ) 0-4 -heteroaryl-aryl, —(CR 245 R 250 ) 0-4 -heteroaryl-heterocyclyl, —(CR 245 R 250 ) 0-4 -heteroaryl-heteroaryl, —(CR 245 R 250 ) 0-4 -heterocyclyl-heteroaryl, —(CR 245 R 250 ) 0-4 -heterocyclyl-heterocyclyl, —(CR 245 R 250 ) 0-4 -heterocyclyl-aryl, —[C(R 255 )(R 260 )] 1-3 —CO—N—(R 255 ) 2 , —CH(aryl) 2 , —CH(heteroaryl) 2 , —CH(heterocyclyl) 2 , —CH(aryl)(heteroaryl), —(CH 2 ) 0-1 —CH((CH 2 ) 0-6 —OH)—(CH 2 ) 0-1 -aryl, —(CH 2 ) 0-1 —CH((CH 2 ) 0-6 —OH)—(CH 2 ) 0-1 -heteroaryl, —CH(-aryl or -heteroaryl)-CO—O(C 1 -C 4 alkyl), —CH(—CH 2 —OH)—CH(OH)-phenyl-NO 2 , (C 1 -C 6 alkyl)-O—(C 1 -C 6 alkyl)-OH; —CH 2 —NH—CH 2 —CH(—O—CH 2 —CH 3 ) 2 , —(CH 2 ) 0-6 —C(═NR 235 )(NR 235 R 240 ), or C —(CH cyclopentyl, cyclohexyl, or cycloheptyl ring fused to aryl, heteroaryl, or heterocyclyl wherein one, two or three carbons of the cyclopentyl, cyclohexyl, or cycloheptyl is optionally replaced with a heteroatom independently selected from NH, NR R 200 at each occurrence is independently selected from —OH, —NO 2 , halogen, —CO 2 H, CNN, C≡N, —(CH 2 ) 0-4 —CO—NR 220 R 225 , —(CH 2 ) 0-4 —CO—(C 1 -C 12 alkyl), —(CH 2 ) 0-4 —CO—(C 2 -C 12 alkenyl), —(CH 2 ) 0-4 —CO—(C 2 -C 12 alkynyl), —(CH 2 ) 0-4 —CO—(C 3 -C 7 cycloalkyl), —(CH 2 ) 0-4 —CO-aryl, —(CH 2 ) 0-4 —CO-heteroaryl, —(CH 2 ) 0-4 —CO-heterocyclyl, —(CH 2 ) 0-4 —CO-—O—R 215 , —(CH 2 ) 0-4 —SO 2 —NR 220 R 225 , —(CH 2 ) 0-4 —SO—(C 1 -C 8 alkyl), —(CH 2 ) 0-4 —SO 2 —(C 1 C 12 alkyl), —(CH 2 ) 0-4 —SO 2 —(C 3 -C 7 cycloalkyl), —(CH 2 ) 0-4 —N(H or R 215 )—CO—O—R 215 , —(CH 2 ) 0-4 —N(H or R 215 )—CO—N(R 215 ) 2 , —(CH 2 ) 0-4 —N—CS—N(R 215 ) 2 , —(CH 2 ) 0-4 —N(—H or R 215 )—CO—R 220 , —(CH 2 ) 0-4 —NR 220 R 225 , —(CH 2 ) 0-4 —O—CO—(C 1 -C 6 alkyl), —(CH 2 ) 0-4 —O—P(O)—(OR 240 ) 2 , —(CH 2 ) 0-4 —O—CO—N(R 215 ) 2 , —(CH 2 ) 0-4 —O—CS—N(R 215 ) 2 , —(CH 2 ) 0-4 —O—(R 215 ), —(CH 2 ) 0-4 —O—(R 215 )—COOH, —(CH 2 ) 0-4 —S—(R 215 ), —(CH 2 ) 0-4 —O—(C 1 -C 6 alkyl optionally substituted with 1, 2, 3, or 5 —F), C 3 -C 7 cycloalkyl, —(CH 2 ) 0-4 —N(H or R 215 )—SO 2 —R 220 , —(CH 2 ) 0-4 —C 3 -C 7 cycloalkyl, C C the aryl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 groups that are independently R the heterocyclyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R R 205 at each occurrence is independently selected from C 1 -C 6 alkyl, halogen, —OH, —O-phenyl, —SH, —S—C 1 -C 6 alkyl, —C≡N, —CF 3 , C 1 -C 6 alkoxy, NH 2 , NH(C 1 -C 6 alkyl) or N—(C 1 -C 6 alkyl)(C 1 -C 6 alkyl); R 210 at each occurrence is independently selected from halogen, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, —NR 220 R 225 , OH, C≡N, —CO—(C 1 -C 4 alkyl), —SO 2 —NR 235 R 240 , —CO—NR 235 R 240 , —SO 2 —(C 1 -C 4 alkyl), ═O, or C R 215 at each occurrence is independently selected from C 1 -C 6 alkyl, —(CH 2 ) 0-2 -(aryl), C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, and —(CH 2 ) 0-2 -(heteroaryl), —(CH 2 ) 0-2 -(heterocyclyl), wherein the aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R the heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 independently selected R R 220 and R 225 at each occurrence are independently selected from —H, —C 3 -C 7 cycloalkyl, —(C 1 -C 2 alkyl)-(C 3 -C 7 cycloalkyl), —(C 1 -C 6 alkyl)-O—(C 1 -C 3 alkyl), —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, —C 1 -C 6 alkyl chain with one double bond and one triple bond, -aryl, -heteroaryl, and -heterocyclyl, and —C the aryl, heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 independently selected R R 235 and R 240 at each occurrence are independently H, or C 1 -C 6 alkyl; R 245 and R 250 at each occurrence are independently selected from —H, C 1 -C 4 alkyl, C 1 -C 4 alkylaryl, C 1 -C 4 alkylheteroaryl, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, —(CH 2 ) 0-4 —C 3 -C 7 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, and phenyl; or R 245 and R 250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms, where one carbon atom is optionally replaced by a heteroatom selected from —O—, —S—, —SO 2 —, and —NR 220 —; R 255 and R 260 at each occurrence are independently selected from —H, —(CH 2 ) 1-2 —S(O) 0-2 —(C 1 -C 6 alkyl), —(C 1 -C 4 alkyl)-aryl, —(C 3 -C 4 alkyl)-heteroaryl, —(C 1 -C 4 alkyl)-heterocyclyl, -aryl, -heteroaryl, -heterocyclyl, —(CH 2 ) 1-4 —R 265 —(CH 2 ) 0-4 -aryl, —(CH 2 ) 1-4 —R 265 —(CH 2 ) 0-4 -heteroaryl, —(CH 2 ) 1-4 —R 265 —(CH 2 ) 0-4 -heterocyclyl, and C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl and —(CH 2 ) 0-4 —C 3 -C 7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from R 205 , —COOH, —COO(C 1 -C 4 alkyl), —CO—NH 2 , —CO—NH(C 1 -C 6 alkyl), —CO—N—(C 1 -C 6 alkyl)(C 1 -C 6 alkyl), wherein each aryl or phenyl is optionally substituted with 1, 2, or 3 groups that are independently R each heterocyclyl is optionally substituted with 1, 2, 3, or 4 R R 265 at each occurrence is independently —O—, —S— or —N(C 1 -C 6 alkyl)-; R 270 at each occurrence is independently R 205 , halogen C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, NR 235 R 240 , —OH, —C≡N, —CO—(C 1 -C 4 alkyl), —SO 2 —NR 235 R 240 , —CO—NR 235 R 240 , —SO 2 —(C 1 -C 4 alkyl), ═O, or C R 5 , R 6 and R 7 , at each occurrence are independently H or —CO—O—(CH 2 ) n8 —R 4-5 where n 8 is 0 thru 2 and R 4-5 is C 1 -C 6 alkyl or phenyl; and R 8 is H or C 1 -C 6 alkyl optionally substituted with one, two or three substituents independently selected from the group consisting of C 1 -C 3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF 3 , C 1 -C 3 alkoxy, —NR 1-a R 1-b where R 1-a and R 1-b are independently —H or C 1 -C 6 alkyl; with the proviso that when R 1 is 1-azepane, R 2 is sec-butyl, R 4 is tert-butyl, R 6 , R 7 , and R 8 are each hydrogen, then R 3 is not 4-benzyloxyphenyl.