2. Academic Validation
  3. Structure based drug design: development of potent and selective factor IXa (FIXa) inhibitors

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

Affiliation

  • 1 Department of Medicinal Chemistry, Trigen Ltd., Emmanuel Kaye Building, 1B Manresa Road,London SW3 6LR, UK. shouming_wang@yahoo.co.uk
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.

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