Phenolic P2/P3 core motif as thrombin inhibitors--design, synthesis, and X-ray co-crystal structure

Stephen Hanessian; Eric Therrien; Willem A L van Otterlo; Malken Bayrakdarian; Ingemar Nilsson; Ola Fjellström; Yafeng Xue

doi:10.1016/j.bmcl.2005.10.082

Phenolic P2/P3 core motif as thrombin inhibitors--design, synthesis, and X-ray co-crystal structure

Bioorg Med Chem Lett. 2006 Feb 15;16(4):1032-6. doi: 10.1016/j.bmcl.2005.10.082. Epub 2005 Nov 15.

Authors

Stephen Hanessian¹, Eric Therrien, Willem A L van Otterlo, Malken Bayrakdarian, Ingemar Nilsson, Ola Fjellström, Yafeng Xue

Affiliation

¹ Department of Chemistry, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, PQ, Canada H3C 3J7. stephen.hanessian@umontreal.ca

PMID: 16290930
DOI: 10.1016/j.bmcl.2005.10.082

Abstract

Prototypical thrombin inhibitors were synthesized based on a trisubstituted phenol as a core motif. A naphthylsulfonamide analogue showed excellent antithrombin activity. An X-ray co-crystal structure showed the expected interactions.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anticoagulants* / chemical synthesis
Anticoagulants* / chemistry
Anticoagulants* / pharmacology
Antithrombins* / chemical synthesis
Antithrombins* / chemistry
Antithrombins* / pharmacology
Crystallography, X-Ray
Drug Design
Models, Molecular
Molecular Structure
Phenols* / chemical synthesis
Phenols* / chemistry
Phenols* / pharmacology
Structure-Activity Relationship
Thrombin / antagonists & inhibitors*

Substances

Anticoagulants
Antithrombins
Phenols
Thrombin