7-Fluoroindazoles as Potent and Selective Inhibitors of Factor Xa†

…, DF McComsey, KL Milkiewicz, CS Crysler…

Index: Lee, Yu-Kai; Parks, Daniel J.; Lu, Tianbao; Thieu, Tho V.; Markotan, Thomas; Pan, Wenxi; McComsey, David F.; Milkiewicz, Karen L.; Crysler, Carl S.; Ninan, Nisha; Abad, Marta C.; Giardino, Edward C.; Maryanoff, Bruce E.; Damiano, Bruce P.; Player, Mark R. Journal of Medicinal Chemistry, 2008 , vol. 51, # 2 p. 282 - 297

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Citation Number: 32

Abstract

We have developed a novel series of potent and selective factor Xa inhibitors that employ a key 7-fluoroindazolyl moiety. The 7-fluoro group on the indazole scaffold replaces the carbonyl group of an amide that is found in previously reported factor Xa inhibitors. The structure of a factor Xa cocrystal containing 7-fluoroindazole 51a showed the 7-fluoro atom hydrogen-bonding with the N–H of Gly216 (2.9 Å) in the peptide backbone. Thus, the 7- ...