Synthesis of 2-Phenylthiazolidine Derivatives as Cardiotonic Agents. V. Modification of the Thiazolidine Moiety of 2- (Phenylpiperazinylalkoxyphenyl) thiazolidine-3-thiocarboxamides and the Corresponding Carboxamides

The carba (2) and oxa analogues (3) of 2- (phenylpiperazinylalkoxyphenyl) thiazolidine-3-carboxamide (1, Y=O) and-thiocarboxamide (1, Y=S) were synthesized and tested for cardiotonic activity. These analogues (2 and 3) were prepared from the aldehydes (4) through several intermediates (7, 10, and 13). In a series of the N-methylcarboxamides, positive inotropic activity in anesthetized dogs decreased in the following order : the thiazolidine (1a) >>oxazolidine (3a) >pyrrolidine (2a). In the corresponding thiocarboxamide series, however, the oxazolidine (3b) was the most potent, followed by the thiazolidine (1b) and the pyrrolidine (2c).