Gunzner-Toste, Janet; Zhao, Guiling; Bauer, Paul; Baumeister, Timm; Buckmelter, Alexandre J.; Caligiuri, Maureen; Clodfelter, Karl H.; Fu, Bang; Han, Bingsong; Ho, Yen-Ching; Kley, Nikolai; Liang, Xiaorong; Liederer, Bianca M.; Lin, Jian; Mukadam, Sophie; O’Brien, Thomas; Oh, Angela; Reynolds, Dominic J.; Sharma, Geeta; Skelton, Nicholas; Smith, Chase C.; Sodhi, Jasleen; Wang, Weiru; Wang, Zhongguo; Xiao, Yang; Yuen, Po-wai; Zak, Mark; Zhang, Lei; Zheng, Xiaozhang; Bair, Kenneth W.; Dragovich, Peter S. published the artcile< Discovery of potent and efficacious urea-containing nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with reduced CYP2C9 inhibition properties>, Reference of 56622-54-9, the main research area is urea containing nicotinamide phosphoribosyltransferase inhibitor reduced CYP2C9 inhibition preparation; pharmacokinetic antitumor activity urea containing benzenesulfonamide.
Potent, reversible inhibition of the cytochrome P 450 CYP2C9 isoform was observed in a series of urea-containing nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. This unwanted property was successfully removed from the described inhibitors through a combination of structure-based design and medicinal chem. activities. An optimized compound, I, which did not inhibit CYP2C9 exhibited potent anti-NAMPT activity (BC NAMPT IC50 = 3 nM; A2780 antiproliferative IC50 = 70 nM), good mouse PK properties, and was efficacious in an A2780 mouse xenograft model. The crystal structure of this compound in complex with the NAMPT protein is also described.
Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 56622-54-9 belongs to class pyridine-derivatives, and the molecular formula is C7H10N2, Reference of 56622-54-9.