Structure-activity relationships of potent and selective factor Xa inhibitors: benzimidazole derivatives with the side chain oriented to the prime site of factor Xa

Hiroshi Ueno; Susumu Katoh; Katsuyuki Yokota; Jun-ichi Hoshi; Mikio Hayashi; Itsuo Uchida; Kazuo Aisaka; Yasunori Hase; Hidetsura Cho

doi:10.1016/j.bmcl.2004.05.092

Structure-activity relationships of potent and selective factor Xa inhibitors: benzimidazole derivatives with the side chain oriented to the prime site of factor Xa

Bioorg Med Chem Lett. 2004 Aug 16;14(16):4281-6. doi: 10.1016/j.bmcl.2004.05.092.

Authors

Hiroshi Ueno¹, Susumu Katoh, Katsuyuki Yokota, Jun-ichi Hoshi, Mikio Hayashi, Itsuo Uchida, Kazuo Aisaka, Yasunori Hase, Hidetsura Cho

Affiliation

¹ Central Pharmaceutical Research Institute, Japan Tobacco Inc, 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.

PMID: 15261287
DOI: 10.1016/j.bmcl.2004.05.092

Abstract

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.

MeSH terms

Benzimidazoles / chemistry*
Factor Xa Inhibitors*
Serine Proteinase Inhibitors / chemistry*
Serine Proteinase Inhibitors / pharmacology*
Structure-Activity Relationship

Substances

Benzimidazoles
Factor Xa Inhibitors
Serine Proteinase Inhibitors