McKew, John C.; Foley, Megan A.; Thakker, Paresh; Behnke, Mark L.; Lovering, Frank E.; Sum, Fuk-Wah; Tam, Steve; Wu, Kun; Shen, Marina W. H.; Zhang, Wen; Gonzalez, Mario; Liu, Shanghao; Mahadevan, Anu; Sard, Howard; Khor, Soo Peang; Clark, James D. published the artcile< Inhibition of Cytosolic Phospholipase A2α: Hit to Lead Optimization>, Category: chlorides-buliding-blocks, the main research area is indole derivative preparation structure phospholipase A2 inhibitor.
Compound (I) was previously reported to be a potent inhibitor of cPLA2α in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC50 of I increased dramatically with cell number or lipid/detergent concentration In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, the authors discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-γ-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA2α inhibition. The IC50s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Three compounds emerged as potent, selective inhibitors of cPLA2α and represent well-validated starting points for further optimization.
Journal of Medicinal Chemistry published new progress about Pharmacophores. 3964-57-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, Category: chlorides-buliding-blocks.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics