Synthesis And Anxiolytic Activity of N-substituted Cyclic Imides (lR*,2s*,3R*,4S*)-: N-[4-[4-(2-pyrimidinyl)-l-piperazinyi]butyl]-2,3-bicyclo[2: 2.1]heptanedicarboximide (tandospirone) And Related Compounds

Abstract

A series of cyclic imides bearing a o>;-(4-aryl and 4-heteroaryl-1-piperazinyl)alkyl moieties was synthesized and tested in vivo for anxiolytic activity. The in vitro binding affinities of these compounds were also examined for 5-HT1A receptor sites. Structure-activity relationships within these series are discussed. One of these compounds, (1 R*,2S*,-3fl*,4S*)-7V-[4-[4-(2-pyrimidinyl)-l-piperazinyl]butyl]-2,3-bicyclo[2.2.1]heptanedicarboximide (1: tandospirone), was found to be equipotent with buspirone in its anxiolytic activity and more anxio-selective than buspirone and diazepam. Tandospirone (1) is currently undergoing clinical evaluation as a selective anxiolytic agent. © 1991, The Pharmaceutical Society of Japan. All rights reserved.