Patent ID: 6369051
Filing Date: 2002-04-09
Classification: A61K

Abstract:
A method for treatment of depression, anxiety, generalized anxiety disorder (GAD), hot flush, post partum depression, premenstrual syndrome, obesity, obsessive compulsive disorder, post-traumatic stress disorder, social phobia, disruptive behavior disorders, impulse control disorders, borderline personality disorder, chronic fatigue disorder, premature ejaculation, pain, attention deficit disorders, with and without hyperactivity, Gilles de la Tourette syndrome, bulimia nervosa, or Shy Drager Syndrome in a mammal, the method comprising administering to a mammal in need thereof a pharmaceutically effective amount of a selective serotonin reuptake inhibitor, or a pharmaceutically acceptable salt thereof, and a pharmaceutically effective amount of a compound of the formulae I or II: wherein Z is a moiety selected from the group of: wherein:R1 is selected from H, OH or the C1-C12 esters or C1-C12 alkyl ethers thereof, benzyloxy, halogen, C1-C4 halogenated ethers, trifluoromethyl ether and trichloromethyl ether, R2, R3, R5 and R6 are independently selected from H, OH or the C1-C12 esters or C1-C12 alkyl ethers thereof, halogens, C1-C4 halogenated ethers, cyano, C1-C6 alkyl, and trifluoromethyl, with the proviso that, when R1 is H, R2 is not OH; R4 is selected from H, OH or the C1-C12 esters or C1-C12 alkyl ethers thereof, halogens, C1-C4 halogenated ethers, benzyloxy, cyano, C1-C6 alkyl, and trifluoromethyl; X is selected from H, C1-C6 alkyl, cyano, nitro, trifluoromethyl, and halogen; n is 1, 2 or 3; Y is selected from: a) the moiety: â€ƒwherein R7 and R8 are independently selected from the group of H, C1-C6 alkyl, and phenyl optionally substituted by CN, C1-C6 alkyl, C1-C6 alkoxy, halogen, â€”OH, â€”CF3, or â€”OCF3; b) a five-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two heteroatoms selected from the group consisting of â€”Oâ€”, â€”NHâ€”, â€”N(C1 C4 alkyl)-, â€”N&boxH;, and â€”S(O)mâ€”, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C1-C4 alkyl, trihalomethyl, C1-C4 alkoxy, trihalomethoxy, C1-C4 acyloxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, hydroxy (C1-C4)alkyl, â€”CO2Hâ€”, â€”CNâ€”, â€”CONHR1â€”, â€”NH2â€”, C1-C4 alkylamino, di(C1-C4)alkylamino, â€”NHSO2R1â€”, â€”NHCOR1â€”, â€”NO2, and phenyl optionally substituted with 1-3 (C1-C4)alkyl; c) a six-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two heteroatoms selected from the group consisting of â€”Oâ€”, â€”NHâ€”, â€”N(C1 C4 alkyl)-, â€”N&boxH;, and â€”S(O)m â€”, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C1-C4 alkyl, trihalomethyl, C1-C4 alkoxy, trihalomethoxy, C1-C4 acyloxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, hydroxy (C1-C4)alkyl, â€”CO2Hâ€”, â€”CNâ€”, â€”CONHR1â€”, â€”NH2â€”, C1-C4 alkylamino, di(C1-C4)alkylamino, â€”NHSO2â€”, â€”NHCOR1â€”, â€”NO2, and phenyl optionally substituted with 1-3 (C1-C4)alkyl; d) a seven-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two heteroatoms selected from the group consisting of â€”Oâ€”, â€”NHâ€”, â€”N(C1C4 alkyl)-, â€”N&boxH;, and â€”S(O)mâ€”, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C1-C4 alkyl, trihalomethyl, C1-C4 alkoxy, trihalomethoxy, C1-C4 acyloxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, hydroxy (C1-C4)alkyl, â€”CO2Hâ€”, â€”CNâ€”, â€”CONHR1â€”, â€”NH2â€”, C1-C4 alkylamino, di(C1-C4)alkylamino, â€”NHSO2R1â€”, â€”NHCOR1â€”, â€”NO2, and phenyl optionally substituted with 1-3 (C1-C4)alkyl; or e) a bicyclic heterocycle containing from 6-12 carbon atoms either bridged or fused and containing up to two heteroatoms selected from the group consisting of â€”Oâ€”, â€”NHâ€”, â€”N(C1C4 alkyl)-, and â€”S(O)mâ€”, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C1-C4 alkyl, trihalomethyl, C1-C4 alkoxy, trihalomethoxy, C1-C4 acyloxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, hydroxy (C1-C4)alkyl, â€”CO2Hâ€”, â€”CNâ€”, â€”CONHR1â€”, â€”NH2â€”, C1-C4 alkylamino, di(C1-C4)alkylamino, â€”NHSO2R1â€”, â€”NHCOR1â€”, â€”NO2, and phenyl optionally substituted with 1-3 (C1-C4) alkyl; or a pharmaceutically acceptable salt thereof.