Document Report Card

ID: ALA1146071

Journal: J Med Chem

Title: 2,4-diaminopyrimidine derivatives as potent growth hormone secretagogue receptor antagonists.

Authors: Serby MD, Zhao H, Szczepankiewicz BG, Kosogof C, Xin Z, Liu B, Liu M, Nelson LT, Kaszubska W, Falls HD, Schaefer V, Bush EN, Shapiro R, Droz BA, Knourek-Segel VE, Fey TA, Brune ME, Beno DW, Turner TM, Collins CA, Jacobson PB, Sham HL, Liu G.

Abstract: Ghrelin, a gut-derived orexigenic hormone, is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Centrally administered ghrelin has been shown to cause hunger and increase food intake in rodents. Inhibition of ghrelin actions with ghrelin antibody, peptidyl GHS-R antagonists, and antisense oligonucleosides resulted in weight loss and food intake decrease in rodents. Here we report the effects of GHS-R antagonists, some of which were potent, selective, and orally bioavailable. A structure-activity relationship study led to the discovery of 8a, which was effective in decreasing food intake and body weight in several acute rat studies.

CiteXplore: 16610800

DOI: 10.1021/jm0510934