Cinnamylindoline derivatives: synthesis and factor Xa (FXa) inhibitory activities.
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.
Noguchi
Tetsuji
T
Medicinal Chemistry Research Laboratories II, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Tanaka
Naoki
N
Nishimata
Toyoki
T
Goto
Riki
R
Hayakawa
Miho
M
Sugidachi
Atsuhiro
A
Ogawa
Taketoshi
T
Asai
Fumitoshi
F
Fujimoto
Koichi
K
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
D000925:Anticoagulants; D002934:Cinnamates; D065427:Factor Xa Inhibitors; D007211:Indoles; D014357:Trypsin