Author/Authors :
Thomas D. Penning، نويسنده , , Mark A. Russell، نويسنده , , Barbara B. Chen، نويسنده , , Helen Y. Chen، نويسنده , , Bipin N. Desai، نويسنده , , Stephen H. Docter، نويسنده , , David J. Edwards، نويسنده , , Glen J. Gesicki، نويسنده , , Chi-Dean Liang، نويسنده , , James W. Malecha، نويسنده , , Stella S. Yu، نويسنده , , V.Wayne Engleman، نويسنده , , Sandra K. Freeman، نويسنده , , Melanie L. Hanneke، نويسنده , , Kristen E. Shannon، نويسنده , , Marisa M. Westlin، نويسنده , , G.Allen Nickols، نويسنده ,
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 αvβ3 and greater than 200-fold selectivity against the other β3 integrin αIIbβ3. In whole 293 cells, many of these analogues also showed modest selectivity against other αv integrins such as αvβ1 and αvβ5. These compounds were synthesized from readily available starting materials using either Heck or Mitsunobu coupling conditions.
