Design, synthesis, and evaluation of oxyanion-hole selective inhibitor substituents for the S1 subsite of factor Xa

…, O Lee, Q Sheng, WT Fu, DC Mulhearn, D Crich…

Index: Rumthao, Sochanchingwung; Lee, Oukseub; Sheng, Qi; Fu, Wentao; Mulhearn, Debbie C.; Crich, David; Mesecar, Andrew D.; Johnson, Michael E. Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 20 p. 5165 - 5170

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Citation Number: 9

Abstract

We have designed, synthesized, and evaluated the factor Xa inhibitory activities of p- amidinophenyl-sulfones, amines, and alcohols intended to take advantage of the polarity and hydrogen-bonding potential of the oxyanion hole region of the S1 specificity pocket. We demonstrate that placement of an anionic group within the oxyanion hole region of the catalytic site substantially enhances activity, with small flexible groups favored over bulkier ...