Development of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5-diones as orally active human chymase inhibitors

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

doi:10.1016/j.bmcl.2007.03.085

Development of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5-diones as orally active human chymase inhibitors

Bioorg Med Chem Lett. 2007 Jun 15;17(12):3435-9. doi: 10.1016/j.bmcl.2007.03.085. Epub 2007 Mar 30.

Authors

Hiroshi Maruoka¹, Tsuyoshi Muto, Taisaku Tanaka, Seiichi Imajo, Yoshiaki Tomimori, Yoshiaki Fukuda, Takashi Nakatsuka

Affiliation

¹ Biomedical Research Laboratories, Daiichi Asubio Pharma Co., Ltd, Mishima-gun, Osaka 618-8513, Japan. [email protected]

PMID: 17434735
DOI: 10.1016/j.bmcl.2007.03.085

Abstract

A novel series of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5-diones was designed, synthesized, and evaluated as human chymase inhibitors. From this series, we identified several compounds which were effective, via oral administration, in a mouse model of chronic dermatitis.

MeSH terms

Administration, Oral
Animals
Azepines / chemical synthesis
Azepines / pharmacology*
Benzyl Compounds / chemical synthesis
Benzyl Compounds / pharmacology*
Binding Sites
Chymases / antagonists & inhibitors*
Dermatitis / drug therapy*
Dermatitis / pathology
Disease Models, Animal
Humans
Inhibitory Concentration 50
Mice
Models, Chemical
Serine Proteinase Inhibitors / chemical synthesis
Serine Proteinase Inhibitors / pharmacology*
Serine Proteinase Inhibitors / therapeutic use
Structure-Activity Relationship

Substances

Azepines
Benzyl Compounds
Serine Proteinase Inhibitors
Chymases