Design and synthesis of potent thiol-based inhibitors of endothelin converting enzyme-1

Autor:	Arco Y. Jeng, Ying Qiao, Paula Savage, Michael A. Moskal, Michael E. Beil, Angelo J. Trapani, Fariborz Firooznia, Hoyer Denton W, Cynthia A. Fink, Dongchu Wei, David Symonsbergen
Rok vydání:	2000
Předmět:	Endothelin converting enzyme 1 Stereochemistry Clinical Biochemistry Pharmaceutical Science Endothelin-Converting Enzymes Thioester Biochemistry Chemical synthesis Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Animals Aspartic Acid Endopeptidases Humans Structure–activity relationship Protease Inhibitors Sulfhydryl Compounds education Molecular Biology chemistry.chemical_classification education.field_of_study biology Organic Chemistry Metalloendopeptidases Rats Enzyme chemistry Enzyme inhibitor Drug Design biology.protein Molecular Medicine Endothelin receptor Derivative (chemistry)
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 10:2037-2039
ISSN:	0960-894X
DOI:	10.1016/s0960-894x(00)00403-0
Popis:	Through directed screening of compounds prepared as metalloprotease inhibitors a compound, CGS 30084 , that had potent endothelin converting enzyme-1 (ECE-1) in vitro inhibitory activity (IC 50 =77 nM) was identified. Herein we report the synthesis and optimization of ECE-1 inhibitory activity of additional analogues from this lead. Compound 3c , the thioacetate methyl ester derivative of compound 4c , was found to be a long acting inhibitor of ECE-1 activity in rats after oral administration.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eb38dc1440f5ad74bbac9edd81f558df https://doi.org/10.1016/s0960-894x(00)00403-0 Zobrazit plný text záznamu Full Text from ScienceDirect