Novel optimised quinuclidine squalene synthase inhibitors

✍ Scribed by George R. Brown; Alan J. Foubister; Susan Freeman; Fergus McTaggart; Donald J. Mirrlees; Alan C. Reid; Graham J. Smith; Melvyn J. Taylor; Douglas A. Thomason; Paul R.O. Whittamore

• Book ID: 104364867
• Publisher: Elsevier Science
• Year: 1997
• Tongue: English
• Weight: 221 KB
• Volume: 7
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/s0960-894x(97)00053-x

✦ Synopsis

Optimised quinuclidine squalene synthase (SQS) inhibitors are reported; 3-[2-(2-allyl-4-(2-ethoxy carbonylethyl)phenyl)ethynyl]quinuclidin-3-ol lc, is a potent inhibitor of rat (KI = 6 nM) and human (KI = 43 nM) microsomal SQS; the oral EDso of lc, for the inhibition of rat cholesterol biosynthesis was 1.3_+0.45 mg/kg and for the R-enantiorner lm, 0.8_+0.2 mg/kg, with the corresponding R-carboxylic acid 6a, being 0.9-t_-0.25 mg/kg.