Structure-activity relationships of potent and selective factor Xa inhibitors: benzimidazole derivatives with the side chain oriented to the prime site of factor Xa.
A series of benzimidazole derivatives with the side chain on the nitrogen atom oriented to the prime site of factor Xa (FXa) were designed and synthesized. Compounds with substituted aminocarbonylmethyl groups as the side chain showed potent FXa inhibitory activity. Compounds 1 and 2 exhibited most potent inhibitory activity and were effective as anticoagulants in a DIC model.
Ueno
Hiroshi
H
Central Pharmaceutical Research Institute, Japan Tobacco Inc, 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
Katoh
Susumu
S
Yokota
Katsuyuki
K
Hoshi
Jun-ichi
J
Hayashi
Mikio
M
Uchida
Itsuo
I
Aisaka
Kazuo
K
Hase
Yasunori
Y
Cho
Hidetsura
H
D001562:Benzimidazoles / Q000737:chemistry*; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors