Sharma, Lalit Kumar; Yun, Mi Kyung; Subramanian, Chitra; Tangallapally, Rajendra; Jackowski, Suzanne; Rock, Charles O.; White, Stephen W.; Lee, Richard E. published an article in 2021. The article was titled 《LipE guided discovery of isopropylphenyl pyridazines as pantothenate kinase modulators》, and you may find the article in Bioorganic & Medicinal Chemistry.Category: pyrimidines The information in the text is summarized as follows:
Pantothenate kinase (PANK) is the critical regulator of intracellular levels of CoA and has emerged as an attractive target for treating neurol. and metabolic disorders. This report describes the optimization, synthesis, and full structure-activity relationships of a new chem. series of pantothenate competitive PANK inhibitors. Potent drug-like mols. were obtained by optimizing a high throughput screening hit, using lipophilic ligand efficiency (LipE) derived from human PANK3 IC50 values to guide ligand development. X-ray crystal structures of PANK3 with index inhibitors from the optimization were determined to rationalize the emerging structure activity relationships. The anal. revealed a key bidentate hydrogen bonding interaction between pyridazine and R306′ as a major contributor to the LipE gain observed in the optimization. A tractable series of PANK3 modulators with nanomolar potency, excellent LipE values, desirable physicochem. properties, and a well-defined structural binding mode was produced from this study. The experimental process involved the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Category: pyrimidines)
2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Category: pyrimidines
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia