Molecular design and structure--activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664

  • Bioorg Med Chem Lett. 2002 Jan 7;12(1):45-9. doi: 10.1016/s0960-894x(01)00667-9.
Jagabandhu Das  1 ,  S David Kimball ,  Steven E Hall ,  Wen Ching Han ,  Edwin Iwanowicz ,  James Lin ,  Robert V Moquin ,  Joyce A Reid ,  John S Sack ,  Mary F Malley ,  Chiehying Y Chang ,  Saeho Chong ,  David B Wang-Iverson ,  Daniel G M Roberts ,  Steven M Seiler ,  William A Schumacher ,  Martin L Ogletree
Affiliations
  • 1. Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA. [email protected]
PMID: 11738570 DOI: 10.1016/s0960-894x(01)00667-9
Abstract

A series of structurally novel small molecule inhibitors of human alpha-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 alpha-thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models.

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