2-(2-Chloro-6-fluorophenyl) acetamides as potent thrombin inhibitors

L Lee, KD Kreutter, W Pan, C Crysler, J Spurlino…

Index: Lee, Lily; Kreutter, Kevin D.; Pan, Wenxi; Crysler, Carl; Spurlino, John; Player, Mark R.; Tomczuk, Bruce; Lu, Tianbao Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 22 p. 6266 - 6269

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Citation Number: 21

Abstract

2-(2-Chloro-6-fluorophenyl) acetamides having 2, 2-difluoro-2-aryl/heteroaryl-ethylamine P3 and oxyguanidine P1 substituents are potent thrombin inhibitors (Ki= 0.9–33.9 nM). 2-(5- Chloro-pyridin-2-yl)-2, 2-difluoroethylamine was the best P3 substituent, yielding the most potent inhibitor (Ki= 0.7 nM). Replacing the P3 heteroaryl group with a phenyl ring or replacing the difluoro substitution with dimethyl or cyclopropyl groups in the linker reduced ...