Title of article :
Synthesis, evaluation, and crystallographic analysis of L-371,912: A potent and selective active-site thrombin inhibitor
Author/Authors :
Terry A. Lyle، نويسنده , , Zhongguo Chen، نويسنده , , Sandra D. Appleby، نويسنده , , Roger M. Freidinger، نويسنده , , Stephen J. Gardell، نويسنده , , S. Dale Lewis، نويسنده , , Ying Li، نويسنده , , Elizabeth A. Lyle، نويسنده , , Joseph J. Lynch Jr.، نويسنده , , Anne M. Mulichak، نويسنده , , Assunta S. Ng، نويسنده , , Adel M. Naylor-Olsen، نويسنده , , William M. Sanders، نويسنده ,
Abstract :
Removal of the β-ketoamide functionality from L-370,518 (Ki = 0.09 nM) provided a 5 nM Ki inhibitor of thrombin: L-371,912. Comparison of the enzyme-inhibitor crystal structures suggests a possible explanation for the relatively small change in affinity for thrombin. L-371,912 is selective for thrombin over related serine proteases and is efficacious in an animal model of arterial thrombosis.
