In 2022,Akiu, Mayuko; Tsuji, Takashi; Sogawa, Yoshitaka; Terayama, Koji; Yokoyama, Mika; Asano, Daigo; Honda, Tomohiro; Ishizaka, Tomomichi; Hasegawa, Tomoko; Pinkerton, Anthony B.; Nakamura, Tsuyoshi published an article in Heterocycles. The title of the article was 《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》.Product Details of 4248-19-5 The author mentioned the following 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. After reading the article, we found that the author used tert-Butyl carbamate(cas: 4248-19-5Product Details of 4248-19-5)
tert-Butyl carbamate(cas: 4248-19-5) belongs to anime. To avoid the problem of multiple alkylation, methods have been devised for “blocking” substitution so that only one alkyl group is introduced. The Gabriel synthesis is one such method; it utilizes phthalimide, C6H4(CO)2NH, whose one acidic hydrogen atom has been removed upon the addition of a base such as KOH to form a salt.Product Details of 4248-19-5
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics