The discovery and synthesis of potent zwitterionic inhibitors of renin

Autor:	Stephen M. Soisson, Tom Y.-H. Wu, Michel Gallant, Austin Chen, Dwight Macdonald, Daniel Dube, Robert Houle, Jean-Pierre Falgueyret, Renee Aspiotis, Dan McKay, Jean-François Lévesque, Patrick Roy, Helene Juteau, Sébastien Gagné, M. David Percival, Erich L. Grimm, Sebastien Laliberte, Patrick Lacombe, Elizabeth Cauchon
Rok vydání:	2011
Předmět:	Stereochemistry Carboxylic acid Clinical Biochemistry hERG Drug Evaluation Preclinical Administration Oral Pharmaceutical Science Biochemistry Chemical synthesis Rats Sprague-Dawley Structure-Activity Relationship chemistry.chemical_compound Dogs Piperidines Catalytic Domain Renin Drug Discovery Animals Humans Structure–activity relationship Computer Simulation Protease Inhibitors Molecular Biology chemistry.chemical_classification biology Organic Chemistry Prodrug Rats Enzyme chemistry Enzyme inhibitor Zwitterion biology.protein Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 21:2430-2436
ISSN:	0960-894X
Popis:	The incorporation of a carboxylic acid within in a series of 3-amido-4-aryl substituted piperidines (represented by general structure 32) led to the discovery of potent, zwitterionic, renin inhibitors with improved off-target profiles (CYP3A4 time-dependent inhibition and hERG affinity) relative to analogous non-zwitterionic inhibitors of the past (i.e., 3). Strategies to address the oral absorption of these zwitterions are also discussed within.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5869451b5d4a9f35f5a8af8a027ba80 https://doi.org/10.1016/j.bmcl.2011.02.067 Zobrazit plný text záznamu Full Text from ScienceDirect