TOCOLYTIC OXYTOCIN RECEPTOR ANTAGONISTS

摘要

Compounds of the formula X-Y-Z-R1, wherein X is (I) or (II); W is hydrogen or acetate; Y is -CO-, -SO¿2?- -CO(CH2)m- or -(CH2)m-; Z is N, O, S, -CHR-, -CR=CH-, -CH=, -(CH2)m- or -CHCHOH-; R is hydrogen, C1-5 alkyl, C1-5 alkoxycarbonylamino or quinuclidinylaminocarbonylamino; R?1¿ is -CH¿3?, -CH(CH3)2, C1-5 alkoxycarbonyl; aryl, heterocyclic and lowercycloalkyl substituted by R?2¿ and/or R?3, -NR4R5¿ or -NCOR6; R2 is hydrogen, hydroxy, carboxyl, acetyl, nitro, halogen, mono-, di- or tri-C¿1-3? alkyl, spirocyclic indenyl, N-spiroindanepiperidinyl, O-R where R is as defined above, O-Het where Het is imidazole or benzimidazole or azimidobenzene, or where R?2¿ is further defined as -COR6, -(CH¿2?)m-NHCOR?7¿, -(CH¿2?)mNHCOOR?7¿, -(CH¿2?)m-NR?8R9¿, -(CH¿2?)m-NHCO-(CH2)mR?7¿, -(CH¿2?)m-NHCO-CHR?7R7¿, -(CH¿2?)m-NHCO-CH=CHR?7¿, -(CH¿2?)m-CO-O-R?7¿, -(CH¿2?)m-CO-O-(CH2)mR?7¿, -(CH¿2?)m-CO-O-CHR?7R7¿, -(CH)¿m?-CO-O-CH=CHR?7¿, -NHSO¿2?R- where R is as defined above, NHSO2R?7¿, -(CH¿2?)m-O-R?10, -SO¿2R?10, -COR11¿, aryl loweralkyl, alkylsulfonylalkyl, alkylsulfonylalkylamido, R3 is one or two of hydrogen, hydroxyl or C¿1-5? alkyl; R?4¿ is hydrogen, C¿1-5? alkyl, or C6-10 cycloalkyl; R?5¿ is hydrogen or acetyl; R6 is (A) or (B); R7 is alkylcarbamate alkyl, aryl alkyl or heterocyclyl alkyl substituted by R12, hydrogen, C¿1-4? alkyl, NSO2R?12¿ or NHO-C¿1-4? alkyl; R?8¿ is hydrogen or C¿1-5? alkyl; R?9¿ is hydrogen or C¿1-5? alkyl; R?10¿ is -CH¿3?, alkaryl, alkarylalkyl or azimidobenzene; R?11¿ is -CH¿3?, aralkyl or heterocyclylalkyl; R?12¿ is hydrogen, C¿1-5? alkyl or C1-5 alkoxy; and m is an integer of from 0 to 5. Such compounds are useful as oxytocin and vasopressin antagonists.