Bioorganic & Medicinal Chemistry 2009-12-15

Design, synthesis, and SAR of cis-1,2-diaminocyclohexane derivatives as potent factor Xa inhibitors. Part II: exploration of 6-6 fused rings as alternative S1 moieties.

Kenji Yoshikawa, Shozo Kobayashi, Yumi Nakamoto, Noriyasu Haginoya, Satoshi Komoriya, Toshiharu Yoshino, Tsutomu Nagata, Akiyoshi Mochizuki, Kengo Watanabe, Makoto Suzuki, Hideyuki Kanno, Toshiharu Ohta

Index: Bioorg. Med. Chem. 17(24) , 8221-33, (2009)

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Abstract

A series of cis-1,2-diaminocyclohexane derivatives possessing a 6-6 fused ring for the S1 moiety were synthesized as novel factor Xa (fXa) inhibitors. The synthesis, structure-activity relationship (SAR), and physicochemical properties are reported herein, together with the discovery of compound 45c, which has potent anti-fXa activity, good physicochemical properties and pharmacokinetic (PK) profiles, including a reduced negative food effect.