Patent ID: 8048895

Claim:
A kappa opioid receptor antagonist compound represented by the formula (I): wherein G is H, OH, OC 1-6 alkyl, OCOC 1-8 alkyl, CONH 2 , NHCHO, NH 2 , NHSO 2 C 1-8 alkyl, or NHCO 2 C 1-8 alkyl; R 1 is C 1-8 alkyl, or one of the following structures: each Y 1 is, independently, H, Br, Cl, F, CN, CF 3 , NO 2 , N 3 , OR 8 , CO 2 R 9 , C 1-6 alkyl, NR 10 R 11 , NHCOR 12 , NHCO 2 R 12 , CONR 13 R 14 , or CH 2 (CH 2 ) n Y 2 , or two adjacent Y 1 groups form a —O—CH 2 —O— or —O—CH 2 CH 2 —O— group; each Y 2 is, independently, H, CF 3 , CO 2 R 9 , C 1-6 alkyl, NR 10 R 11 , NHCOR 12 , NHCO 2 R 12 , CONR 13 R 14 , CH 2 OH, CH 2 OR 8 , or COCH 2 R 9 ; Y 3 is H, Br, Cl, F, CN, CF 3 , NO 2 , N 3 , OR 8 , CO 2 R 9 , C 1-6 alkyl, NR 10 R 11 , NHCOR 12 , NHCO 2 R 12 , CONR 13 R 14 , or CH 2 (CH 2 ) n Y 2 ; R 2 is H, C 1-8 alkyl, C 3-8 alkenyl, C 3-8 alkynyl or CH 2 -aryl substituted by one or more groups Y 1 ; R 3 is H, C 1-8 alkyl, C 3-8 alkenyl, C 3-8 alkynyl or CH 2 -aryl substituted by one or more groups Y 1 ; wherein R 2 and R 3 may be bonded together to form a C 2-8 , alkyl group; R 4 is hydrogen, C 1-8 alkyl, CO 2 C 1-8 alkylaryl substituted by one or more groups Y 1 , CH 2 -aryl substituted by one or more groups Y 1 or CO 2 C 1-8 alkyl; Z is N, O or S, wherein when Z is O or S, there is no R 5 ; R 5 is H, C 1-8 alkyl, C 3-8 alkenyl, C 3-8 alkynyl, CH 2 CO 2 C 1-8 alkyl, CO 2 C 1-8 alkyl or CH 2 -aryl substituted by one or more groups Y 1 ; n is 0, 1, 2 or 3; o is 0, 1, 2, or 3; R 6 is a group selected from the group consisting of structures (a)-(p): Q is NR 7 , CH 2 , O, S, SO, or SO 2 ; each Y 4 is, independently, H, Br, Cl, F, CN, CF 3 , NO 2 , N 3 , OR 8 , CO 2 R 9 , C 1-6 alkyl, NR 10 R 11 , NHCOR 12 , NHCO 2 R 12 , CONR 13 R 14 , or CH 2 (CH 2 ) n Y 2 , or two adjacent Y 4 groups form a —O—CH 2 —O— or —O—CH 2 CH 2 —O— group; p is 0, 1, 2, or 3; Y 5 is H, Br, Cl, F, CN, CF 3 , NO 2 , N 3 , OR 8 , CO 2 R 9 , C 1-6 alkyl, NR 10 R 11 , NHCOR 12 , NHCO 2 R 12 , CONR 13 R 14 , or CH 2 (CH 2 ) n Y 2 ; X 1 is hydrogen, C 1-8 alkyl, C 3-8 alkenyl, or C 3-8 alkynyl; X 2 is hydrogen, C 1-8 alkyl, C 3-8 alkenyl, or C 3-8 alkynyl; or X 1 and X 2 together form ═O, ═S, or ═NH; R 7 is H, C 1-8 alkyl, CH 2 -aryl substituted by one or more substituents Y 1 , NR 10 R 11 , NHCOR 12 , NHCO 2 R 13 , CONR 14 R 15 , CH 2 (CH 2 ) n Y 2 , or C(═NH)NR 16 R 17 ; each of R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 is, independently, H, C 1-8 alkyl, CH 2 -aryl substituted by one or more substituents H, OH, Br, Cl, F, CN, CF 3 , NO 2 , N 3 , C 1-6 alkyl, or CH 2 (CH 2 ) n Y 2 ′; Y 2 ′ is H, CF 3 , or C 1-6 alkyl; R 18 is C 1-8 alkyl, C 2-8 alkenyl, C 3-8 alkenyl, CH 2 OR 5 , or CH 2 -aryl substituted by one or more substituents Y 1 ; or a pharmaceutically acceptable salt thereof.