Literature

Abstract

Preliminary hit-to-lead optimization of a novel series of phenylsulfonyl hydrazide derivatives, which were derived from the high throughput screening hit compound 1 (IC50=5700nM against PGE2 production), for a potent suppressor of PGE2 production is described. Subsequent optimization led to the identification of the potent lead compound 8n with IC50 values of 4.5 and 6.9nM, respectively, against LPS-induced PGE2 production and NO production in RAW 264.7 macrophage cells. In addition, 8n was about 30- and >150-fold more potent against mPGES-1 enzyme in a cell-free assay (IC50=70nM) than MK-886 and hit compound 1, respectively. Molecular docking suggests that compound 8n could inhibit PGE2 production by blocking the PGH2 binding site of human mPGES-1 enzyme.

DOI： 10.1016/j.bmcl.2015.11.024

Hit-to-lead optimization of phenylsulfonyl hydrazides for a potent suppressor of PGE2 production: Synthesis, biological activity, and molecular docking study

Bioorganic & Medicinal Chemistry Letters 2016.0

Synthesis, structure determination, and biological evaluation of phenylsulfonyl hydrazide derivatives as potential anti-inflammatory agents

Bioorganic & Medicinal Chemistry Letters 2016.0

Identification of novel mPGES-1 inhibitors through screening of a chemical library

Bioorganic & Medicinal Chemistry Letters 2012.0

Synthesis and PGE2 production inhibition of s-triazine derivatives as a novel scaffold in RAW 264.7 macrophage cells

Bioorganic & Medicinal Chemistry Letters 2014.0

Synthesis and pharmacological characterization of benzenesulfonamides as dual species inhibitors of human and murine mPGES-1

Bioorganic & Medicinal Chemistry 2013.0

Discovery of Highly Potent Microsomal Prostaglandin E<sub>2</sub> Synthase 1 Inhibitors Using the Active Conformation Structural Model and Virtual Screen