title: Stereoselective synthesis and biological evaluation of 3,4-diaminocyclohexanecarboxylic acid derivatives as factor Xa inhibitors.
abstract: There have been few reports on synthetic methods for cis-1,2-diaminocyclohexane bearing a third ring substituent. Starting from 3-cyclohexenecarboxylic acid, we developed efficient methods for synthesizing the 3,4-diaminocyclohexanecarboxylic acid derivatives 2-5. We also evaluated their anti-Xa and anticoagulant activities. Among the compounds, acid 2a and amide 2b exhibited the most potent in vitro anti-fXa activity, indicating that the position and stereochemistry of a polar functional group on the cyclohexane ring greatly affected the in vitro anti-fXa activity.
authors.affiliation: Medicinal Chemistry Research Laboratories I, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. nagata.tsutomu.ni@daiichisankyo.co.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nagata
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nagamochi
authors.forename: Shozo
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Komoriya
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yoshino
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kanno
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000990:Antithrombin III / Q000737:chemistry / Q000494:pharmacology; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003510:Cyclohexanes / Q000737:chemistry; D003514:Cyclohexylamines / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D015951:Factor Xa / Q000737:chemistry; D065427:Factor Xa Inhibitors; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D052160:Benzothiazoles; D002264:Carboxylic Acids; D003510:Cyclohexanes; D003514:Cyclohexylamines; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors; C506365:Cyclohexane; D000990:Antithrombin III; D015951:Factor Xa