Sharma, Lalit Kumar published the artcileLipE guided discovery of isopropylphenyl pyridazines as pantothenate kinase modulators, Related Products of pyrimidines, the main research area is isopropylphenyl pyridazine derivative panthothenate kinase lipophilic ligand efficiency; Hit-to-lead; Lipophilic ligand efficiency; Pantothenate Kinase; Pyridazine.
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.
Bioorganic & Medicinal Chemistry published new progress about Crystal structure. 38275-56-8 belongs to class pyrimidines, name is 5-Chloropyrimidine-2-carbonitrile, and the molecular formula is C5H2ClN3, Related Products of pyrimidines.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia