Synthesis and biological evaluations of condensed pyridine and condensed pyrimidine-based HMG-CoA reductase inhibitors

Citation
M. Suzuki et al., Synthesis and biological evaluations of condensed pyridine and condensed pyrimidine-based HMG-CoA reductase inhibitors, BIOORG MED, 11(10), 2001, pp. 1285-1288
Citations number
16
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960-894X → ACNP
Volume
11
Issue
10
Year of publication
2001
Pages
1285 - 1288
Database
ISI
SICI code
0960-894X(20010521)11:10<1285:SABEOC>2.0.ZU;2-D
Abstract
A series of 3,5-dihydroxyheptenoic acid derivatives containing pyrazolopyri dine, isoxazolopyridine, thienopyridine, and pyrazolopyrimidine as a key sc affold was synthesized from condensed pyridine and condensed pyrimidine car boxylic acid esters by homologation, aldol condensation with ethyl acetoace tate dianion, and stereoselective reduction of the 5-hydroxyketone. Several compounds in the series were found to have potent HMG-CoA reductase inhibi tory activities in vitro and marked cholesterol biosynthesis inhibitory act ivities in vivo. It has been shown that these scaffolds can be used as a su itable replacement for the hexahydronaphthalene ring present in naturally o ccurring HMG-CoA reductase inhibitors. (C) 2001 Elsevier Science Ltd. All r ights reserved.