1392138-96-3

Basic information

• Product Name: C₂₃H₂₄FN₃O₂S
• Synonyms: C₂₃H₂₄FN₃O₂S
• CAS NO: 1392138-96-3
• Molecular Weight: 425.527
• Mol File: 1392138-96-3.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: C₂₃H₂₄FN₃O₂S(CAS DataBase Reference)
• NIST Chemistry Reference: C₂₃H₂₄FN₃O₂S(1392138-96-3)
• EPA Substance Registry System: C₂₃H₂₄FN₃O₂S(1392138-96-3)

Safety Data

• Hazardous Substances Data: 1392138-96-3(Hazardous Substances Data)

Upstream product

• 1392139-25-1 (Z)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxylic acid 
• 22795-97-7 (R)-2-aminomethyl-1-ethylpyrrolidine 
• 272437-84-0 3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxylic acid 

Relevant articles and documents

Discovery of a Plasmodium falciparum Glucose-6-phosphate Dehydrogenase 6-phosphogluconolactonase Inhibitor (R,Z)-N-((1-Ethylpyrrolidin-2-yl)methyl)-2- (2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (ML276) that reduces parasite growth in vitro

A high-throughput screen of the NIH's MLSMR collection of ～340000 compounds was undertaken to identify compounds that inhibit Plasmodium falciparum glucose-6-phosphate dehydrogenase (Pf G6PD). PfG6PD is important for proliferating and propagating P. falciparum and differs structurally and mechanistically from the human orthologue. The reaction catalyzed by glucose-6-phosphate dehydrogenase (G6PD) is the first, rate-limiting step in the pentose phosphate pathway (PPP), a key metabolic pathway sustaining anabolic needs in reductive equivalents and synthetic materials in fast-growing cells. In P. falciparum, the bifunctional enzyme glucose-6-phosphate dehydrogenase-6- phosphogluconolactonase (Pf GluPho) catalyzes the first two steps of the PPP. Because P. falciparum and infected host red blood cells rely on accelerated glucose flux, they depend on the G6PD activity of PfGluPho. The lead compound identified from this effort, (R,Z)-N-((1-ethylpyrrolidin-2-yl)methyl)-2-(2- fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carbox-amide, 11 (ML276), is a submicromolar inhibitor of PfG6PD (IC50 = 889 nM). It is completely selective for the enzyme's human isoform, displays micromolar potency (IC50 = 2.6 μM) against P. falciparum in culture, and has good drug-like properties, including high solubility and moderate microsomal stability. Studies testing the potential advantage of inhibiting Pf G6PD in vivo are in progress.