NOVEL OPTIMIZED QUINUCLIDINE SQUALENE SYNTHASE INHIBITORS

Authors
BROWN GR FOUBISTER AJ FREEMAN S MCTAGGART F MIRRLEES DJ REID AC SMITH GJ TAYLOR MJ THOMASON DA WHITTAMORE PRO
Citation
Gr. Brown et al., NOVEL OPTIMIZED QUINUCLIDINE SQUALENE SYNTHASE INHIBITORS, Bioorganic & medicinal chemistry letters, 7(5), 1997, pp. 597-600
Citations number
13
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
7
Issue
5
Year of publication
1997
Pages
597 - 600
Database
ISI
SICI code
0960-894X(1997)7:5<597:NOQSSI>2.0.ZU;2-#
Abstract
Optimised quinuclidine squalene synthase (SQS) inhibitors are reported ; 3-[2-(2-allyl-4-(2-ethoxy carbonylethyl)phenyl)ethynyl]quinuclidin-3 -ol 1c, is a potent inhibitor of rat (KI = 6 nM) and human (KI = 43 nM ) microsomal SQS; the oral ED(50) of 1c, for the inhibition of rat cho lesterol biosynthesis was 1.3+/-0.45 mg/kg and for the R-enantiomer 1m , 0.8+/-0.2 mg/kg, with the corresponding R-carboxylic acid 6a, being 0.9+/-0.25 mg/kg. (C) 1997 Elsevier Science Ltd. All rights reserved.