Synthesis of New Aryl-substituted Tandospirone and Epiboxidine Analogues and Isoxazoline Derivatives

摘要

Tandospirone (1), whose structure and pharmacological properties are similar to those of buspirone (2), is an anxiolytic drug marketed in Japan. Its primary pharmacological action is brought about by its binding to the serotonin (5-HTia) receptor in the brain. There are a few reports on the synthesis of tandospirone analogues where the bicyclic system or pyrimidin-2-yl group of 1 have been changed, and we recently described the synthesis of more bioactive aryl- and heteroaryl substituted tandospirones (3) by reductive Heck reactions and of isoxazoline derivatives (4) via 1,3-dipolar cycloadditions in which the main structure of tandospirone remains unchanged. We became interested in the synthesis of aryl- and heteroaryl substituted tandospirones which have an oxygen bridge and an era-ring at the tricyclic system as possible biologically active molecules.