Synthesis of cinnamic acids and related isosteres as potent and selective alpha v beta 3 receptor antagonists |
| |
Authors: | Penning Thomas D Russell Mark A Chen Barbara B Chen Helen Y Desai Bipin N Docter Stephen H Edwards David J Gesicki Glen J Liang Chi-Dean Malecha James W Yu Stella S Engleman V Wayne Freeman Sandra K Hanneke Melanie L Shannon Kristen E Westlin Marisa M Nickols G Allen |
| |
Institution: | Department of Medicinal Chemistry, Pfizer Global Research & Development, 4901 Searle Parkway, Skokie, IL 60077, USA. thomas.penning@abbott.com |
| |
Abstract: | We describe a series of conformationally-restricted cinnamic acid peptidomimetics as well as several cinnamic acid isosteres, including 3-phenylpropionic acids, 2-amino-3-phenylpropionic acids, phenoxyacetic acids and 2-phenylcyclopropylcarboxylic acids. Several analogues demonstrated low to sub-nanomolar potencies against alpha(v)beta(3) and greater than 200-fold selectivity against the other beta(3) integrin alpha(IIb)beta(3). In whole 293 cells, many of these analogues also showed modest selectivity against other alpha(v) integrins such as alpha(v)beta(1) and alpha(v)beta(5). These compounds were synthesized from readily available starting materials using either Heck or Mitsunobu coupling conditions. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|