Title of article :
De novo design, synthesis, and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold
Author/Authors :
Dominique Potin، نويسنده , , Michele Launay، نويسنده , , Eric Nicolai، نويسنده , , Maud Fabreguette، نويسنده , , Patrice Malabre، نويسنده , , François Caussade، نويسنده , , Dominique Besse، نويسنده , , Stacey Skala، نويسنده , , Dawn K. Stetsko، نويسنده , , Gordon Todderud، نويسنده , , Brett R. Beno، نويسنده , , Daniel L. Cheney، نويسنده , , Chiehying J. Chang، نويسنده , , Steven Sheriff، نويسنده , , Diane L. Hollenbaugh، نويسنده , , Joel C. Barrish، نويسنده , , Edwin J. Iwanowicz، نويسنده , , Suzanne J. Suchard، نويسنده , , T.G. Murali Dhar، نويسنده ,
Abstract :
LFA-1 (leukocyte function-associated antigen-1), is a member of the β2-integrin family and is expressed on all leukocytes. The LFA-1/ICAM interaction promotes tight adhesion between activated leukocytes and the endothelium, as well as between T cells and antigen-presenting cells. Evidence from both animal models and clinical trials provides support for LFA-1 as a target in several different inflammatory diseases. This paper describes the de novo design, synthesis and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold.
