Selective NPY (Y5) antagonists
View Patent ↗This invention is directed to bicyclic and tricyclic compounds which are selective antagonists for NPY (Y5) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therapeutically effective amount of a compound of this invention and a pharmaceutically acceptable carrier. The invention provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention further provides the use of a compound of the invention for the preparation of a pharmaceutical composition for treating an abnormality, wherein the abnormality is alleviated by decreasing the activity of a human Y5 receptor.
1. A method of treating a subject suffering from obesity, which comprises administering to the subject a therapeutically effective amount of a compound having the structure:
wherein each R 14 is independently H, F, Cl, Br, —CN, —NO 2 , —NR 5 R 6 , —SO 2 R 5 —(CH 2 ) n OR 5 , —SO 2 C 6 H 5 , —SO 2 NR 5 R 6 , —(CH 2 ) n CONR 5 R 6 , —(CH 2 ) n NR 5 COR 5 , ethylenedioxy, methylenedioxy, perfluoroalkyl, polyfluoroalkyl, aminoalkyl, or straight chained or branched C 1 -C 7 alkyl; phenyl, or C 1 -C 7 phenylalkyl, wherein the phenyl or C 1 -C 7 phenylalkyl may be substituted with one or more of F, Cl, Br, —CF 3 , —CN, —NO 2 , —NR 5 R 6 , —SO 2 R 5 , —(CH 2 ) n OR 5 , or straight chained or branched C 1 -C 4 alkyl; provided that if one R 14 is phenyl or C 1 -C 7 phenylalkyl, the other R 14 is H;
wherein each R 1 is independently H, F, Cl, Br, —CN, —NO 2 , —NR 5 R 6 , —SO 2 R 5 , —(CH 2 ) n OR 5 , —SO 2 C 6 H 5 , —SO 2 NR 5 R 6 , —(CH 2 ) n CONR 5 R 6 , —(CH 2 ) n NR 5 COR 5 , ethylenedioxy, methylenedioxy, perfluoroalkyl, polyfluoroalkyl, aminoalkyl, or straight chained or branched C 1 -C 7 alkyl; phenyl, or C 1 -C 7 phenylalkyl, wherein the phenyl or C 1 -C 7 phenylalkyl may be substituted with one or more of F, Cl, Br, —CF 3 , —CN, —NO 2 , —NR 5 R 6 , —SO 2 R 5 , —(CH 2 ) n OR 5 , or straight chained or branched C 1 -C 4 alkyl;
wherein R 2 is H, straight chained or branched C 1 -C 4 alkyl, —(CH 2 ) t OR 5 , phenyl optionally substituted with one or more of F, Cl, Br, —CF 3 , —CN, —NO 2 , —NR 5 R 6 , —SO 2 R 5 , —(CH 2 ) n OR 5 , or straight chained or branched C 1 -C 4 alkyl;
wherein R 5 is independently H; or straight chained or branched C 1 -C 7 alkyl;
wherein R 6 is independently H; or straight chained or branched C 1 -C 7 alkyl;
wherein each n independently is an integer from 0 to 6 inclusive;
wherein R 8 is
wherein R 9 independently H; or straight chained or branched C 1 -C 4 alkyl;
wherein R 12 is H, straight chained or branched C 1 -C 7 alkyl or —(CH 2 ) n OR 17 ;
wherein R 13 is independently —(CH 2 ) u OR 5 ; —(CH 2 ) t CONR 5 R 6 ; —(CH 2 ) u NR 5 COR 5 ; —(CH 2 ) t COR 7 ; —(CH 2 ) t CO 2 R 5 ; —(CH 2 ) u NR 5 R 6 ; —(CH 2 ) u CN; straight chained or branched C 1 -C 7 alkyl; C 1 -C 7 alkyl in which the C 2 -C 7 atoms may be optionally substituted with one or more F or Cl; C 3 -C 7 cycloalkyl-C 1 -C 7 alkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; or C 3 -C 7 cycloalkyl; phenyl or C 1 -C 6 phenylalkyl; wherein the phenyl or C 1 -C 6 phenylalkyl may be substituted with one or more of F, Cl, —CN, —NO 2 , —NR 5 R 6 , —SO 2 R 5 , —(CH 2 ) n COR 7 , —(CH 2 ) n OR 5 , —(CH 2 ) n CONR 5 R 6 , —(CH 2 ) n NR 5 COR 5 , —(CH 2 ) n CO 2 R 5 , —(CH 2 ) n SO 2 NR 5 R 6 , straight chained or branched C 1 -C 7 alkyl, perfluoroalkyl, polyfluoroalkyl, or aminoalkyl;
wherein R 7 is independently straight chained or branched C 1 -C 7 alkyl;
wherein R 17 is straight chained or branched C 1 -C 4 alkyl; perfluoroalkyl, or polyfluoroalkyl;
wherein each p independently is an integer from 0 to 2 inclusive;
wherein each r independently is an integer from 0 to 3 inclusive;
wherein t is an integer from 1 to 4 inclusive; and
wherein each u independently is an integer from 2 to 4 inclusive;
or a pharmaceutically acceptable salt thereof.