Discovery and optimization of oxadiazole-based FLAP inhibitors

Autor:	John D. Huber, J. Matthew Hutzler, Doris Riether, Tom Simpson, Alan Olague, Asitha Abeywardane, Renee Zindell, John Broadwater, Peter Allen Nemoto, Hidenori Takahashi, Todd Bosanac, Yunlong Zhang, Alessandra Bartolozzi, Zhidong Chen, Lifen Wu
Rok vydání:	2017
Předmět:	Male 0301 basic medicine ERG1 Potassium Channel 5-Lipoxygenase-Activating Proteins Clinical Biochemistry hERG Drug Evaluation Preclinical Pharmaceutical Science Oxadiazole macromolecular substances 01 natural sciences Biochemistry Rats Sprague-Dawley Inhibitory Concentration 50 Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound In vivo Drug Discovery Animals Humans Structure–activity relationship Rats Wistar Molecular Biology Oxadiazoles biology Chemistry Organic Chemistry Combinatorial chemistry Rats 0104 chemical sciences 010404 medicinal & biomolecular chemistry 030104 developmental biology Solubility 5-Lipoxygenase-Activating Protein Inhibitors Microsomes Liver biology.protein Molecular Medicine Functional activity Half-Life
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 27:4652-4659
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2017.09.007
Popis:	Structure activity relationship (SAR) investigation of an oxadiazole based series led to the discovery of several potent FLAP inhibitors. Lead optimization focused on achieving functional activity while improving physiochemical properties and reducing hERG inhibition. Several compounds with favorable in vitro and in vivo properties were identified that were suitable for advanced profiling.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7409748ad2ed88f5ff75e6fc34d9eca7 https://doi.org/10.1016/j.bmcl.2017.09.007 Zobrazit plný text záznamu Full Text from ScienceDirect