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Akiu, Mayuko; Tsuji, Takashi; Iida, Kouki; Sogawa, Yoshitaka; Terayama, Koji; Yokoyama, Mika; Tanaka, Jun; Asano, Daigo; Honda, Tomohiro; Sakurai, Ken; Pinkerton, Anthony B.; Nakamura, Tsuyoshi
Chemical & pharmaceutical bulletin, 11/2021, Letnik: 69, Številka: 11Journal Article
Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the rate-limiting step of the nicotinamide adenine dinucleotide (NAD+) salvage pathway. Because NAD+ plays a pivotal role in energy metabolism and boosting NAD+ has positive effects on metabolic regulation, activation of NAMPT is an attractive therapeutic approach for the treatment of various diseases, including type 2 diabetes and obesity. Herein we report the discovery of 1-(2-phenyl-1,3-benzoxazol-6-yl)-3-(pyridin-4-ylmethyl)urea 12c (DS68702229), which was identified as a potent NAMPT activator. Compound 12c activated NAMPT, increased cellular NAD+ levels, and exhibited an excellent pharmacokinetic profile in mice after oral administration. Oral administration of compound 12c to high-fat diet-induced obese mice decreased body weight. These observations indicate that compound 12c is a promising anti-obesity drug candidate.
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in: SICRIS
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