Synthesis and biological activity of L-tyrosine-based PPAR gamma agonists with reduced molecular weight

Authors
Liu, KG Lambert, MH Ayscue, AH Henke, BR Leesnitzer, LM Oliver, WR Plunket, KD Xu, HE Sternbach, DD Willson, TM
Citation
Kg. Liu et al., Synthesis and biological activity of L-tyrosine-based PPAR gamma agonists with reduced molecular weight, BIOORG MED, 11(24), 2001, pp. 3111-3113
Citations number
11
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
24
Year of publication
2001
Pages
3111 - 3113
Database
ISI
SICI code
0960-894X(200112)11:24<3111:SABAOL>2.0.ZU;2-I
Abstract
A series of PPAR gamma agonists were synthesized front L-tyrosine that inco rporated low molecular weight N-substituents. The most potent analogue, pyr role (4e), demonstrated a K-i of 6.9 nM and an EC50 of 4.7 nM in PPAR gamma binding and functional assays, respectively. Pyrrole (4e), which is readil y synthesized from L-tyrosine methyl ester in four steps, also demonstrated in vivo activity in a rodent model of Type 2 diabetes. (C) 2001 Elsevier S cience Ltd. All rights reserved.