title: Cinnamylindoline derivatives: synthesis and factor Xa (FXa) inhibitory activities.
abstract: A series of cinnamylindoline derivatives were synthesized, and their factor Xa (FXa) inhibitory activities and selectivity over trypsin were evaluated. Among them, some novel derivatives showed potent FXa inhibitory activities and good selectivity over trypsin. Especially, (E)-2-{5-[1-(acetimidoyl)piperidin-4-yloxy]-2-[2-(5-amidino-2-hydroxyphenyl)ethen-1-yl]indolin-1-ylsulfonyl}acetic acid (22f) having 2-hydroxycinnamyl moiety exhibited the most potent FXa inhibitory activity in vitro. Furthermore, 22f also exhibited potent anticoagulant activities in vitro.
authors.affiliation: Medicinal Chemistry Research Laboratories II, Daiichi 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: Koichi
authors.initials: K
authors.lastname: Fujimoto
mesh_terms: D000925:Anticoagulants / Q000138:chemical synthesis / Q000494:pharmacology*; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D065427:Factor Xa Inhibitors; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D013329:Structure-Activity Relationship; D014357:Trypsin / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D002934:Cinnamates; D065427:Factor Xa Inhibitors; D007211:Indoles; D014357:Trypsin