Abstract: Compounds of the formula: are provided, which are selective kappa opioid receptor antagonists, wherein R1 is (C1-C5)alkyl, C3-C6(cycloalkyl)alkyl, C5-C7(cycloalkenyl)alkyl, (C6-C12)aryl, (C6-C12)aralkyl, trans(C4-C5)alkenyl, allyl or furan-2-ylalkyl, R2 is H, OH or O2C(C1-C5)alkyl; R3 is H, (C6-C10)aralkyl, (C1-C5)alkyl or (C1-C5)alkylCO; X is O, S or NY, wherein Y is H or (C1-C5) alkyl; R4 is CH2 (methylene) or C═O (carbonyl), R5 is CH2, C═O or C═NH (imino) and R6 is (C1-C4)alkyl or NH(C1-C4)alkyl, optionally substituted by a non-terminal (C1-C2)alkyl group or by N(R7)(R8) wherein R7 and R8 are individually H or (C1-C3)alkyl, with the proviso that one of R4 or R5 is CH2, and the pharmaceutically acceptable salts thereof.

Abstract: Compounds of the formula: ##STR1## are provided, which are selective kappa opioid receptor antagonists, wherein R.sup.1 is (C.sub.1 -C.sub.5)alkyl, C.sub.3 -C.sub.6 (cycloalkyl)alkyl, C.sub.5 -C.sub.7 (cycloalkenyl)alkyl, (C.sub.6 -C.sub.12)aryl, (C.sub.6 -C.sub.12)aralkyl, trans (C.sub.4 -C.sub.5) alkenyl, allyl or furan-2-ylalkyl; R.sup.2 is H, OH or O.sub.2 C(C.sub.1 -C.sub.5)alkyl; R.sup.3 is H, (C.sub.6 -C.sub.10)aralkyl, (C.sub.1 -C.sub.5)alkyl or (C.sub.1 -C.sub.5)alkylCO; X is O, S or NY, wherein Y is H or (C.sub.1 -C.sub.5)alkyl; R.sup.4 is CH.sub.2 (methylene) or C.dbd.O (carbonyl), R.sup.5 is CH.sub.2, C.dbd.O or C.dbd.NH (imino) and R.sup.6 is (C.sub.1 -C.sub.4)alkyl or NH(C.sub.1 -C.sub.4)alkyl, optionally substituted by a non-terminal (C.sub.1 -C.sub.2)alkyl group or by N(R.sup.7) (R.sup.8) wherein R.sup.7 and R.sup.8 are individually H or (C.sub.1 -C.sub.3) alkyl, with the proviso that one of R.sup.4 or R.sup.5 is CH.sub.2, and the pharmaceutically acceptable salts thereof.