Warfarin: history, tautomerism and activity

Article

Abstract

The anticoagulant drug warfarin, normally administered as the racemate, can exist in solution in potentially as many as 40 topologically distinct tautomeric forms. Only 11 of these forms for each enantiomer can be distinguished by selected computational software commonly used to estimate octanol–water partition coefficients and/or ionization constants. The history of studies on warfarin tautomerism is reviewed, along with the implications of tautomerism to its biological properties (activity, protein binding and metabolism) and chemical properties (log P, log D, pKa). Experimental approaches to assessing warfarin tautomerism and computational results for different tautomeric forms are presented.

Keywords

Tautomers Warfarin Keto-enol tautomerism Ring-chain tautomerism 

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© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Global Pharmaceutics and Life Cycle Technology, Dept. R43D, Bldg. AP31Abbott LaboratoriesAbbott ParkUSA

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