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Cycloalkanediamine derivatives as novel blood coagulation factor Xa inhibitors
Tsutomu Nagata1, Toshiharu Yoshino, Noriyasu Haginoya
1Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd, 1-16-13, Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan. nagatso1@daiichipharm.co.jp
Abstract:
This paper describes the synthesis of orally available potent fXa inhibitors 2 and 3 by modification of the piperazine part of lead compound 1. Carbonyl derivative 3 showed potent fXa activity but not sulfonyl derivative 2. Among the compounds synthesized, cyclohexane derivatives 3g and 3h and cycloheptane derivative 3j had potent anticoagulant activity as well as anti-fXa activity. Synthetic study of the optical isomers of 3g demonstrated that (-)-3g had more potent activity.
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