Patent ID: 6403611
Filing Date: 2002-06-11
Classification: A61K,A61P

Abstract:
A method of inhibiting a pathological condition which is susceptible or partially susceptible to inhibition by an estrogen, antiestrogen or estrogen agonist, which comprises administering to a mammal in need of inhibition of decreased libido an effective amount of a compound of formula I wherein:A is CH2; B, D and E are CH; Y is (a) phenyl, optionally substituted with 1-3 substituents independently selected from R4; (b) naphthyl, optionally substituted with 1-3 substituents independently selected from R4; (c) C3-C8 cycloalkyl, optionally substituted with 1-2 substituents independently selected from R4; (d) C3-C8 cycloalkenyl, optionally substituted with 1-2 substituents independently selected from R4; (e) a five membered heterocycle containing up to two heteroatoms selected from the group consisting of â€”Oâ€”, â€”NR2â€” and â€”S(O)nâ€”, optionally substituted with 1-3 substituents independently selected from R4; (f) a six membered heterocycle containing up to two heteroatoms selected from the group consisting of â€”Oâ€”, â€”NR2â€” and â€”S(O)nâ€” optionally substituted with 1-3 substituents independently selected from R4; or (g) a bicyclic ring system consisting of a five or six membered heterocyclic ring fused to a phenyl ring, said heterocyclic ring containing up to two heteroatoms selected from the group consisting of â€”Oâ€”, â€”NR2â€”, and â€”S(O)nâ€”, optionally substituted with 1-3 substituents independently selected from R4; Z1 is (a) â€”(CH2)pW(CH2)qâ€”. (b) â€”O(CH2)pCR5R6â€”; (c) â€”O(CH2)pW(CH2)q; (d) â€”OCHR2CHR3â€”; or (e) â€”SCHR2CHR3â€”; G is (a) â€”NR7R8; (b) â€ƒwherein n is 0, 1 or 2; m is 1, 2 or 3; Z2 is â€”NHâ€”, â€”Oâ€”, â€”Sâ€”, or â€”CH2â€”; optionally fused on adjacent carbon atoms with one or two phenyl rings and, optionally independently substituted on carbon with one to three substituents and, optionally, independently on nitrogen with a chemically suitable substituent selected from R4; or (c) a bicyclic amine containing five to twelve carbon atoms, either bridged or fused and optionally substituted with 1-3 substituents independently selected from R4; Z and G in combination may be â€ƒW is (a) â€”CH2â€”; (b) â€”CH&boxH;CHâ€”; (c) â€”Oâ€”; (d) â€”NR2â€”; (e) â€”S(O)nâ€”; (f) (g) â€”CR2(OH)â€”; (h) â€”CONR2â€”; (i) â€”NR2COâ€”; (j) (k) â€”Câ‰¡Câ€”; R is hydrogen or C1-C6 alkyl; R2 and R3 are independently (a) hydrogen; or (b) C1-C4 alkyl; R4 is (a) hydrogen; (b) halogen, (c) C1-C6 alkyl; (d) C1-C4 alkoxy; (e) C1-C4 acyloxy; (f) C1-C4 alkylthio; (g) C1-C4 alkylsulfinyl; (h) C1-C4 alkylsulfonyl; (i) hydroxy (C1-C4)alkyl; (j) aryl (C1-C4)alkyl; (k) â€”CO2H; (l) â€”CN; (m) â€”CONHOR; (n) â€”SO2NHR; (o) â€”NH2; (p) C1-C4 alkylamino; (q) C1-C4 dialkylamino; (r) â€”NHSO2R; (s) â€”NO2; (t) -aryl; or (u) â€”OH. R5 and R6 are independently C1-C8 alkyl or together form a C3-C10 carbocyclic ring; R7 and R8 are independently (a) phenyl; (b) a C3-C10 carbocyclic ring, saturated or unsaturated; (c) a C3-C10 heterocyclic ring containing up to two heteroatoms, selected from â€”Oâ€”, â€”Nâ€” and â€”Sâ€”; (d) H; (e) C1-C6 alkyl; or (f) form a 3 to 8 membered nitrogen containing ring with R5 or R6; R7 and R8 in either linear or ring form may optionally be substituted with up to three substituents independently selected from C1-C6 alkyl, halogen, alkoxy, hydroxy and carboxy; a ring formed by R7 and R8 may be optionally fused to a phenyl ring; e is 0, 1 or 2; m is 1, 2 or 3; n is 0, 1 or 2; p is 0, 1, 2 or 3; q is 0, 1, 2 or 3; or an optical or a geometric isomer thereof; or a nontoxic pharmacologically acceptable acid addition salt, N-oxide, ester, or quaternary ammonium salt thereof.