Synthesis and biological evaluation of quinuclidine derivatives incorporating phenothiazine moieties as squalene synthase inhibitors

…, H Kakuta, H Moritani, T Ugawa, I Yanagisawa

Index: Ishihara, Tsukasa; Kakuta, Hirotoshi; Moritani, Hiroshi; Ugawa, Tohru; Yanagisawa, Isao Chemical and Pharmaceutical Bulletin, 2004 , vol. 52, # 10 p. 1204 - 1209

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Citation Number: 28

Abstract

Squalene synthase inhibitors have the potential to be superior hypocholesterolemic agents. A series of quinuclidine derivatives incorporating phenothiazine systems was synthesized in order to investigate the effects of their structure on the inhibition of hamster liver microsomal enzyme.(±)-3-(10-Methyl-10H-phenothiazin-3-ylmethoxy) quinuclidine hydrochloride (19) was the most potent inhibitor in this series with an IC 50 value of 0.12 μM. Oral dosing of ...