Title of article :
Molecular design and structure–Activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664
Author/Authors :
Jagabandhu Das، نويسنده , , S. David Kimball، نويسنده , , Steven E. Hall، نويسنده , , Wen-Ching Han، نويسنده , , Edwin Iwanowicz، نويسنده , , Ming-Ji James Lin، نويسنده , , Robert V. Moquin، نويسنده , , Joyce A. Reid، نويسنده , , John S. Sack، نويسنده , , Mary F. Malley، نويسنده , , Chiehying Y. Chang، نويسنده , , Saeho Chong، نويسنده , , David B. Wang-Iverson، نويسنده , , Daniel G. M. Roberts، نويسنده , , Steven M. Seiler، نويسنده , , William A. Schumacher، نويسنده , , Martin L. Ogletree، نويسنده ,
Abstract :
A series of structurally novel small molecule inhibitors of human α-thrombin was prepared to elucidate their structure–activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human α-thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models.
