| Literature DB >> 32550996 |
Michael B Plewe1, Nadezda V Sokolova1, Vidyasagar Reddy Gantla1, Eric R Brown1, Shibani Naik1, Alexandra Fetsko1, Donald D Lorimer2,3, David M Dranow2,3, Hayden Smutney2,4, Jameson Bullen2,3, Rana Sidhu2,4, Arshil Master2,4, Junru Wang2,4, E Adam Kallel5, Lihong Zhang6, Birte Kalveram6, Alexander N Freiberg6,6, Greg Henkel1, Ken McCormack1.
Abstract
We identified and explored the structure-activity-relationship (SAR) of an adamantane carboxamide chemical series of Ebola virus (EBOV) inhibitors. Selected analogs exhibited half-maximal inhibitory concentrations (EC50 values) of ∼10-15 nM in vesicular stomatitis virus (VSV) pseudotyped EBOV (pEBOV) infectivity assays, low hundred nanomolar EC50 activity against wild type EBOV, aqueous solubility >20 mg/mL, and attractive metabolic stability in human and nonhuman liver microsomes. X-ray cocrystallographic characterizations of a lead compound with the EBOV glycoprotein (GP) established the EBOV GP as a target for direct compound inhibitory activity and further provided relevant structural models that may assist in identifying optimized therapeutic candidates.Entities:
Year: 2020 PMID： 32550996 PMCID： PMC7294737 DOI： 10.1021/acsmedchemlett.0c00025
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345