title: Indoline derivatives I: synthesis and factor Xa (FXa) inhibitory activities.
abstract: A series of bisamidine derivatives each having a ring structure in the center of the molecule was synthesized and their Factor Xa (FXa) inhibitory activities were evaluated. Among them, some indoline derivatives showed potent inhibitory activities in vitro. In particular, (R)-18a having an (R)-configuration at the 2-position of the indoline ring exhibited the most potent FXa inhibitory activity in vitro, more potent than DX-9065a. Furthermore, (R)-18a exhibited more potent anticoagulant activity than DX-9065a. We also succeeded in obtaining an X-ray crystal structure of FXa bound with (R)-18a.
authors.affiliation: Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd, Tokyo, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Noguchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Toyoki
authors.initials: T
authors.lastname: Nishimata
authors.forename: Riki
authors.initials: R
authors.lastname: Goto
authors.forename: Miho
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Sugidachi
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Ogawa
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Asai
authors.forename: Yumi
authors.initials: Y
authors.lastname: Matsui
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujimoto
mesh_terms: D000328:Adult; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006224:Cricetinae; D018360:Crystallography, X-Ray; D065427:Factor Xa Inhibitors; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D065427:Factor Xa Inhibitors; D007202:Indicators and Reagents; D007211:Indoles; C057812:indoline