Structure based drug design: development of potent and selective factor IXa (FIXa) inhibitors

  • J Med Chem. 2010 Feb 25;53(4):1473-82. doi: 10.1021/jm901476x.
Shouming Wang  1 ,  Richard Beck ,  Andrew Burd ,  Toby Blench ,  Frederic Marlin ,  Tenagne Ayele ,  Stuart Buxton ,  Claudio Dagostin ,  Maja Malic ,  Rina Joshi ,  John Barry ,  Mohammed Sajad ,  Chiming Cheung ,  Shaheda Shaikh ,  Suresh Chahwala ,  Chaman Chander ,  Christine Baumgartner ,  Hans-Peter Holthoff ,  Elizabeth Murray ,  Michael Blackney ,  Amanda Giddings
Affiliations
  • 1. Department of Medicinal Chemistry, Trigen Ltd., Emmanuel Kaye Building, 1B Manresa Road,London SW3 6LR, UK. [email protected]
PMID: 20121197 DOI: 10.1021/jm901476x
Abstract

On the basis of our understanding on the binding interactions of the benzothiophene template within the FIXa active site by X-ray crystallography and molecular modeling studies, we developed our SAR strategy by targeting the 4-position of the template to access the S1 beta and S2-S4 sites. A number of highly selective and potent Factor Xa (FXa) and FIXa inhibitors were identified by simple switch of functional groups with conformational changes toward the S2-S4 sites.