Synthesis and structure-activity relationships of a new class of 1-oxacephem-based human chymase inhibitors

Y Aoyama; M Uenaka; T Konoike; Y Iso; Y Nishitani; A Kanda; N Naya; M Nakajima

doi:10.1016/s0960-894x(00)00488-1

Synthesis and structure-activity relationships of a new class of 1-oxacephem-based human chymase inhibitors

Bioorg Med Chem Lett. 2000 Nov 6;10(21):2397-401. doi: 10.1016/s0960-894x(00)00488-1.

Authors

Y Aoyama¹, M Uenaka, T Konoike, Y Iso, Y Nishitani, A Kanda, N Naya, M Nakajima

Affiliation

¹ Shionogi Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan. yasunori.aoyama@shionogi.co.jp

PMID: 11078187
DOI: 10.1016/s0960-894x(00)00488-1

Abstract

1-Oxacephem derivatives were synthesized and evaluated as a novel series of chymase inhibitors. Structure-activity relationship studies of 1-oxacephems led to compound 34, which exhibited 6 nM inhibition of human chymase and high selectivity for human chymase compared to other serine enzymes.

MeSH terms

Cephalosporins / chemical synthesis*
Cephalosporins / chemistry
Cephalosporins / pharmacology
Chymases
Drug Design
Humans
Molecular Structure
Serine Endopeptidases / chemistry
Serine Endopeptidases / metabolism*
Serine Proteinase Inhibitors / chemical synthesis*
Serine Proteinase Inhibitors / chemistry
Serine Proteinase Inhibitors / metabolism
Serine Proteinase Inhibitors / pharmacology
Structure-Activity Relationship

Substances

Cephalosporins
Serine Proteinase Inhibitors
Serine Endopeptidases
Chymases