Bonacchi G, Agostini O, Fedi M, Bacciarelli C, Boni P, Castellucci A, Perretti F, Manzini S
Chemistry Department, Istituto Farmacobiologico Malesci S.p.A., Firenze, Italy.
Arzneimittelforschung. 1988 May;38(5):650-4.
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.
已完成α-肾上腺素能受体拮抗剂IP-66（1-[2-乙氧基-2-(3'-吡啶基)乙基]-4-(2'-甲氧基苯基)哌嗪）及其中间体IP-30（1-[2-羟基-2-(3'-吡啶基)乙基]-4-(2'-甲氧基苯基)哌嗪）光学异构体的拆分。通过高压液相色谱法测定光学纯度。比较了外消旋混合物和立体异构体对苯肾上腺素和去甲肾上腺素诱导的离体大鼠主动脉条收缩的拮抗效力。(+)-IP-66和(+)-IP-30在引发竞争性α1-肾上腺素能受体阻滞方面分别比各自的(-)异构体强363倍和170倍。同样，IP-66(+)或(+/-)在拮抗去甲肾上腺素诱导的脊髓麻醉大鼠升压反应方面比(-)异构体极其有效得多。
