Resolution and pharmacological properties of the enantiomers of the potent alpha-adrenoceptor antagonist 1-[2-ethoxy-2- (3'-pyridyl) ethyl]-4- (2'-methoxy-phenyl) piperazine
Bonacchi, G.; Agostini, O.; Fedi, M.; Bacciarelli, C.; Boni, P.; Castellucci, A.; Perretti, F.; Manzini, S.
Arzneimittel-Forschung 38(5): 650-654
1988
ISSN/ISBN: 0004-4172 PMID: 2901262 Document Number: 309184
Resolution of the optical isomers of the alpha-adrenoceptor antagonist IP-66 (1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine) and its intermediate IP-30 (1-[2-hydroxy-2-(3'-pyridyl)ethyl]-4- (2'-methoxy-phenyl)piperazine have been carried out. Optical purity was assayed by high-pressure liquid chromatography. The antagonistic potencies of racemic mixtures and stereoisomers toward phenylephrine- and norepinephrine-induced contraction in isolated rat aortic strips have been compared. (+)-IP-66 and (+)-IP-30 were resp. 363 and 170 times more potent than respective (-) isomers in eliciting competitive alpha 1-adrenoceptor blockade. Similarly IP-66 (+) or (+/-) were extremely more effective than the (-) isomer in antagonizing norepinephrine-induced pressor responses in pithed rat.