Structure-based design of cycloamide–urethane-derived novel inhibitors of human brain memapsin 2 (β-secretase)

Autor:	Thippeswamy Devasamudram, Christopher B. DeZutter, Vajira Weerasena, Lin Hong, Jordan Tang, Gerald Koelsch, Geoffrey Bilcer, Xiaoming Xu, Arun K. Ghosh
Rok vydání:	2005
Předmět:	Stereochemistry Clinical Biochemistry Substituent Pharmaceutical Science Crystallography X-Ray Urethane Biochemistry Chemical synthesis chemistry.chemical_compound Endopeptidases Drug Discovery Hydrolase Amyloid precursor protein Aspartic Acid Endopeptidases Humans Protease Inhibitors Molecular Biology Molecular Structure biology Organic Chemistry Brain Amides Ring size chemistry Enzyme inhibitor biology.protein Lactam Molecular Medicine Amyloid Precursor Protein Secretases Amyloid precursor protein secretase
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 15:15-20
ISSN:	0960-894X
Popis:	A series of novel macrocyclic amide-urethanes was designed and synthesized based upon the X-ray crystal structure of our lead inhibitor (1, OM99-2 with eight residues) bound to memapsin 2. Ring size and substituent effects have been investigated. Cycloamide-urethanes containing 14- to 16-membered rings exhibited low nanomolar inhibitory potencies against human brain memapsin 2 (beta-secretase).
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5d5f5d5d592fdf40726ab8abaf39068d https://doi.org/10.1016/j.bmcl.2004.10.084 Zobrazit plný text záznamu Full Text from ScienceDirect