title: Cycloalkanediamine derivatives as novel blood coagulation factor Xa inhibitors.
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.
authors.affiliation: Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd, 1-16-13, Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan. nagatso1@daiichipharm.co.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nagata
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yoshino
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Haginoya
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Isobe
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Furugohri
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kanno
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology*; D001682:Biological Availability; D003516:Cycloparaffins / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D065427:Factor Xa Inhibitors; D000882:Haplorhini; D006801:Humans; D008862:Microsomes, Liver; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000925:Anticoagulants; D003516:Cycloparaffins; D065427:Factor Xa Inhibitors