Optimization of NAMPT (Nicotinamide phosphoribosyltransferase) activators: discovery of N,N-diethyl-1,2-benzoxazole-3-carboxamide derivatives as potent NAMPT activators with mitigated mutagenic risks was written by Akiu, Mayuko;Tsuji, Takashi;Sogawa, Yoshitaka;Terayama, Koji;Yokoyama, Mika;Asano, Daigo;Honda, Tomohiro;Ishizaka, Tomomichi;Hasegawa, Tomoko;Pinkerton, Anthony B.;Nakamura, Tsuyoshi. And the article was included in Heterocycles in 2022.Reference of 109-85-3 The following contents are mentioned in the article:
DS68702229, a potent NAMPT activator developed from HTS followed by a hit-to-lead campaign, is a promising candidate compound that significantly reduced body weight when orally administered to mice with high fat diet-induced obesity. However, in vitro toxicol. profiling of DS68702229 revealed bacterial mutagenicity using Salmonella typhimurium TA98 and TA100 strains upon S9 activation. Hypothesizing that DNA intercalation is the likely cause, we employed several approaches to disrupt the putative DNA intercalation, including modulation of the mol. shape. Our efforts culminated in the discovery of compounds 20k and 20l, which increased intracellular NAD+ levels in a cell-based assay without inducing mutagenicity, along with acceptable plasma exposure in mice after oral administration. This study involved multiple reactions and reactants, such as 2-Methoxyethylamine (cas: 109-85-3Reference of 109-85-3).
2-Methoxyethylamine (cas: 109-85-3) belongs to ethers. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits, including apples, durians, pears, bananas, pineapples, and strawberries. Cyclic esters are called lactones, regardless of whether they are derived from an organic or inorganic acid. One example of an organic lactone is γ-valerolactone.Reference of 109-85-3
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem