Global Pharmaceutics and Life Cycle Technology, Dept. R43D, Bldg. AP31, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064, USA.
J Comput Aided Mol Des. 2010 Jun;24(6-7):553-73. doi: 10.1007/s10822-010-9335-7. Epub 2010 Mar 30.
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, pK (a)). Experimental approaches to assessing warfarin tautomerism and computational results for different tautomeric forms are presented.
抗凝药物华法林通常以外消旋体给药，在溶液中可能存在多达 40 种潜在拓扑上不同的互变异构形式。对于每个对映异构体，通常用于估计辛醇-水分配系数和/或离解常数的选定计算软件只能区分其中的 11 种形式。本文回顾了华法林互变异构的研究历史，以及互变异构对其生物学性质（活性、蛋白结合和代谢）和化学性质（log P、log D、pK(a)）的影响。本文还介绍了评估华法林互变异构的实验方法和不同互变异构形式的计算结果。
