Pyrrolidinyl and pyrrolinyl ethylamine compounds as kappa agonists

Abstract

A compound of the following formula: and the salts thereof, wherein A is hydrogen, halo, hydroxy, or the like; the broken line represents an optional double bond with proviso that if the broken line is a double bond, then A is absent; Ar1 is optionally substituted phenyl or the like; Ar2 is aryl or heteroaryl selected from phenyl, napththyl, pyridyl, and the like, the aryl or heteroaryl being optionally substituted; R1 is hydrogen, hydroxy, C1-C4 alkyl, or the like; and R2 and R3 are independently selected from optionally substituted C1-C7 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkenyl, and the like or R2 and R3, together with the nitrogen atom to which they are attached, form an optionally substituted pyrrolidine, piperidine or morpholine ring. These compounds are useful as kappa agonists.

Description

[0001] This invention relates to novel pyrrolidinyl and pyrrolinyl ethylamine compounds and their pharmaceutically acceptable salts, and to pharmaceutical compositions containing them. The pharmaceutically active compounds of tics invention can be used as a selective kappa-receptor agonist.[0002] Opioid analgesics such as morphine are therapeutically useful, but their usage is strictly limited because of their side effects such as drug dependency and abuse. Thus, analgesics with high usefulness and reduced tendency to cause drug dependency are desired. Considerable pharmacological and biochemical studies have been carried out to discover the opioid peptides and opioid receptors, and the discovery of the subtype of opioid receptor such as mu (.mu.), delta (.delta.), kappa (.kappa.) in a variety of species, including human, has made a beginning towards creating new analgesics. As it is thought that opioid analgesics such as morphine act as a mu-receptor agonist, separating the action ...

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