BENZAMIDINE DERIVATIVES

摘要

Benzamidine derivatives of the formula I are useful delta-opioid receptor modulators, agonists useful as analgesics and antagonists useful as immunosuppressants, antiinflammatory agents, agents for the treatment of neurological and psychiatric conditions medicaments for drug and alcohol abuse, agents for treating gastritis and diarrhea, cardiovascular agents and agents for the treatment of respiratory diseases. Wherein: X is a substituent selected from the group consisting of S and O; Z is a substituent selected from the group consisting of O(R5) and N(R6)(R7); the moiety -C(X)Z is substituted on the phenyl at the 3 or 4 position; n is an integer from 1 to 2; R1 is a substituent selected from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy(C1-6)alkyl, C1-6alkoxycarbonyl, C1-6alkyl(C1-6)alkoxycarbonyl, formyl, aryl, aryl(C1-6)alkyl, diaryl(C1-6)alkyl and heteroaryl(C1-6)alkyl; wherein aryl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of halogen, C1-4alkyl, C1-4alkoxy, amino, C1-4alkylamino, di(C1-4alkyl)amino, thrihaloC1-4alkyl and trihaloC1-4alkoxy; R2 and R3 are substituents independently selected from the group consisting of hydrogen and C1-6alkyl; Ar is aryl optionally substituted with one to three substituents selected from R4; R4 is a substituent selected from the group consisting of halogen, C1-6alkyl, C1-6alkoxy, aryl, aryl(C1-6)alkyl, heteroaryl, heteroaryl(C1-6)alkyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, nitro, trihaloC1-4alkyl and trihaloC1-4alkoxy; alternatively, two R4 substituents may be fused together on adjacent carbon atoms to form a single fused moiety, wherein the moiety is selected from the group consisting of -(CH2)3-5- and -O(CH2)1-3O-; R5 is a substituent selected from C1-6alkyl; and R6 and R7 are substituents independently selected from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, aryl and aryl(C1-6)alkyl, wherein cycloalkyl and aryl are optionally substituted with one to three substituents independently selected from the group consisting of halogen, C1-4alkyl,C2-4alkenyl, C1-4alkoxy, C3-7cycloalkyl, trihaloC1-3alkyl and trihaloC1-3alkoxy; alternatively, R6 and R7 may be fused together to form a single fused moiety, wherein the moiety is selected from the group consisting of -(CH2)3-5- and O(CH2)1-3O-; and pharmaceutically acceptable enantiomers, diastereomers and salts thereof.