title: 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.
abstract: 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.
authors.affiliation: R&D Division, Daiichi Sankyo Co, Ltd, 1-16-13, Kita-Kasai, Tokyo 134-8630, Japan. yoshikawa.kenji.t6@daiichisankyo.co.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Shozo
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Yumi
authors.initials: Y
authors.lastname: Nakamoto
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Haginoya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Komoriya
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yoshino
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nagata
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Mochizuki
authors.forename: Kengo
authors.initials: K
authors.lastname: Watanabe
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kanno
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ohta
mesh_terms: D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology; D000990:Antithrombin III / Q000627:therapeutic use; D001665:Binding Sites; D003514:Cyclohexylamines / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D015394:Molecular Structure; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D000925:Anticoagulants; D003514:Cyclohexylamines; D000990:Antithrombin III; C030435:1,2-cyclohexanediamine