Zheng, Xiaozhang published the artcileStructure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors, Category: imidazoles-derivatives, the main research area is amide containing nicotinamide phosphoribosyltransferase inhibitor preparation cancer.
Crystal structures of several urea- and thiourea-derived compounds in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein were utilized to design a potent amide-containing inhibitor bearing an aza-indole moiety (Nampt BC IC50 = 9.0 nM, A2780 cell proliferation IC50 = 10 nM). A Nampt cocrystal structure was subsequently obtained and enabled the design of addnl. amide-containing inhibitors which incorporated various other fused 6,5-heterocyclic moieties and biaryl sulfone or sulfonamide motifs. Addnl. modifications of these mols. afforded many potent biaryl sulfone-containing Nampt inhibitors which also exhibited favorable in vitro ADME properties (microsomal and hepatocyte stability, MDCK permeability, plasma protein binding). An optimized compound was a potent inhibitor of multiple cancer cell lines (IC50 <10 nM vs U251, HT1080, PC3, MiaPaCa2, and HCT116 lines), displayed acceptable mouse PK properties (F = 41%, CL = 52.4 mL/min/kg), and exhibited robust efficacy in a U251 mouse xenograft model. Journal of Medicinal Chemistry published new progress about Antitumor agents. 588720-29-0 belongs to class imidazoles-derivatives, name is Imidazo[1,5-a]pyridine-7-carboxylic acid, and the molecular formula is C8H6N2O2, Category: imidazoles-derivatives.
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem