- Design, synthesis, and SAR of cis-1,2-diaminocyclohexane derivatives as potent factor Xa inhibitors. Part I: exploration of 5-6 fused rings as alternative S1 moieties.
Design, synthesis, and SAR of cis-1,2-diaminocyclohexane derivatives as potent factor Xa inhibitors. Part I: exploration of 5-6 fused rings as alternative S1 moieties.
Bioorganic & medicinal chemistry (2009-11-04)
Kenji Yoshikawa, Aki Yokomizo, Hiroyuki Naito, Noriyasu Haginoya, Shozo Kobayashi, Toshiharu Yoshino, Tsutomu Nagata, Akiyoshi Mochizuki, Ken Osanai, Kengo Watanabe, Hideyuki Kanno, Toshiharu Ohta
PMID19884015
摘要
A series of cis-1,2-diaminocyclohexane derivatives were synthesized with the aim of optimizing previously disclosed factor Xa (fXa) inhibitors. The exploration of 5-6 fused rings as alternative S1 moieties resulted in two compounds which demonstrated improved solubility and reduced food effect compared to the clinical candidate, compound A. Herein, we describe the synthesis and structure-activity relationship (SAR), together with the physicochemical properties and pharmacokinetic (PK) profiles of some prospective compounds.