- 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.
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.
Bioorganic & medicinal chemistry (2009-11-11)
Kenji Yoshikawa, Shozo Kobayashi, Yumi Nakamoto, Noriyasu Haginoya, Satoshi Komoriya, Toshiharu Yoshino, Tsutomu Nagata, Akiyoshi Mochizuki, Kengo Watanabe, Makoto Suzuki, Hideyuki Kanno, Toshiharu Ohta
PMID19900814
摘要
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.