Identification of orally bioavailable, non-amidine inhibitors of Urokinase Plasminogen Activator (uPA)

Autor:	Gary Phillips, Rebecca Pulk, Christopher W. West, Danny Arnaiz, Shendong Yuan, Kieu Chu, Marc Adler, David R. Light, Deborah Chen, Elena Ho, Giovanna Gualtieri, Marc Whitlow, Christoph Huwe, Judi Bryant, Drew Sukovich
Rok vydání:	2009
Předmět:	Benzylamines Serine Proteinase Inhibitors Clinical Biochemistry Amidines Pharmaceutical Science Administration Oral Crystallography X-Ray Biochemistry Chemical synthesis Amidine chemistry.chemical_compound Structure-Activity Relationship Oral administration Drug Discovery medicine Structure–activity relationship Animals Humans Binding site Molecular Biology Urokinase chemistry.chemical_classification Serine protease Binding Sites biology Chemistry Organic Chemistry Urokinase-Type Plasminogen Activator Rats Enzyme biology.protein Molecular Medicine medicine.drug
Zdroj:	Bioorganicmedicinal chemistry letters. 19(19)
ISSN:	1464-3405
Popis:	In this Letter we report the synthesis and evaluation of a series of non-amidine inhibitors of Urokinase Plasminogen Activator (uPA). Starting from compound 1, a significant change provided compounds in which the amidine, binding in the S1 pocket, was replaced with a primary amine. Further modifications led to the identification of potent, selective, and orally bioavailable uPA inhibitors.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::60747fc1bc1095b1d652f959205693a8 https://pubmed.ncbi.nlm.nih.gov/19703768 Zobrazit plný text záznamu Full Text from ScienceDirect