《Identification and structure-activity relationship exploration of uracil-based benzoic acid and ester derivatives as novel dipeptidyl Peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus》 was written by Li, Qing; Deng, Xiaoyan; Jiang, Neng; Meng, Liuwei; Xing, Junhao; Jiang, Weizhe; Xu, Yanjun. Recommanded Product: Methyl 3-(bromomethyl)benzoateThis research focused onuracil benzoic acid ester dipeptidyl peptidase inhibitor diabetes mellitus; Benzoic acid; DPP-4 inhibitor; Ester; SAR exploration; Type 2 diabetes. The article conveys some information:
Our previously reported carboxyl-containing DPP-4 inhibitors were highly potent but were poorly bioavailable. Esters of the carboxyl analogs exhibited a significant DPP-4 potency loss albeit with enhanced oral absorption. Herein, we described identification and structure-activity relationship (SAR) exploration of a novel series of benzoic acid and ester derivatives as low single-digit nanomolar DPP-4 inhibitors. Importantly, the esters displayed comparable activities to the acids counterparts. Mol. simulation revealed that ester adopts a similar binding mode to acid. Moreover, the selected esters and acids demonstrated high selectivity and low cytotoxicity, as well as good metabolic stability. And more importantly, the esters possessed excellent pharmacokinetic profiles for oral administration. The best compound ester 19b demonstrated long DPP-4 inhibition in vivo, and robustly improved the glucose tolerance in normal and db/db mice while ensuring glucose-lowering potency in chronic treatment. Our results supported that the compound 19b can be served as a potential candidate for the treatment of type 2 diabetes. In the experiment, the researchers used many compounds, for example, Methyl 3-(bromomethyl)benzoate(cas: 1129-28-8Recommanded Product: Methyl 3-(bromomethyl)benzoate)
Methyl 3-(bromomethyl)benzoate(cas: 1129-28-8) belongs to organobromine compounds. A variety of minor organobromine compounds are found in nature, but none are biosynthesized or required by mammals. The most pervasive is the naturally produced bromomethane.Recommanded Product: Methyl 3-(bromomethyl)benzoate
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary