Identification of 6-substituted 4-arylsulfonyl-1,4-diazepane-2,5-diones as a novel scaffold for human chymase inhibitors

Taisaku Tanaka; Tsuyoshi Muto; Hiroshi Maruoka; Seiichi Imajo; Harukazu Fukami; Yoshiaki Tomimori; Yoshiaki Fukuda; Takashi Nakatsuka

doi:10.1016/j.bmcl.2007.03.038

Identification of 6-substituted 4-arylsulfonyl-1,4-diazepane-2,5-diones as a novel scaffold for human chymase inhibitors

Bioorg Med Chem Lett. 2007 Jun 15;17(12):3431-4. doi: 10.1016/j.bmcl.2007.03.038. Epub 2007 Mar 16.

Authors

Taisaku Tanaka¹, Tsuyoshi Muto, Hiroshi Maruoka, Seiichi Imajo, Harukazu Fukami, Yoshiaki Tomimori, Yoshiaki Fukuda, Takashi Nakatsuka

Affiliation

¹ Biomedical Research Laboratories, Daiichi Asubio Pharma Co., Ltd, 1-1-1 Wakayamadai Shimamoto-cho, Mishima-gun, Osaka 618-8513, Japan. tanaka.taisasku.fu@asubio.co.jp

PMID: 17419055
DOI: 10.1016/j.bmcl.2007.03.038

Abstract

A novel series of 6-substituted 4-sulfonyl-1,4-diazepane-2,5-diones were designed, synthesized and evaluated as human chymase inhibitors. Structure-activity relationship studies led to the identification of a potent inhibitor, (6S)-6-(5-chloro-2-methoxybenzyl)-4-[(4-chlorophenyl)sulfonyl]-1,4-diazepane-2,5-dione, with an IC(50) of 0.027 microM.

MeSH terms

Azepines / chemical synthesis
Azepines / pharmacology*
Chymases / antagonists & inhibitors*
Humans
Inhibitory Concentration 50
Models, Chemical
Serine Proteinase Inhibitors / chemical synthesis
Serine Proteinase Inhibitors / pharmacology*
Structure-Activity Relationship

Substances

Azepines
Serine Proteinase Inhibitors
Chymases