Grignard-mediated synthesis and preliminary biological evaluation of novel3-substituted farnesyl diphosphate analogues

Authors
Zahn, TJ Weinbaum, C Gibbs, RA
Citation
Tj. Zahn et al., Grignard-mediated synthesis and preliminary biological evaluation of novel3-substituted farnesyl diphosphate analogues, BIOORG MED, 10(15), 2000, pp. 1763-1766
Citations number
24
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
10
Issue
15
Year of publication
2000
Pages
1763 - 1766
Database
ISI
SICI code
0960-894X(20000807)10:15<1763:GSAPBE>2.0.ZU;2-O
Abstract
A series of substituents was installed at the 3 position of farnesyl diphos phate through a copper-cyanide mediated coupling of a vinyl triflate with v arious Grignard reagents. These novel FPP mimetics were then evaluated as i nhibitors of or substrates for mammalian protein farnesyl transferase. The IC50 values for these compounds range from 18 to 10,100 nm, with the 3-isop ropenyl analogue being one of the most potent FPP-mimetic mFTase inhibitors yet synthesized. (C) 2000 Elsevier Science Ltd. All rights reserved. (C) 2 000 Elsevier Science Ltd. All rights reserved.