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New highly potent dipeptidic growth hormone secretagogues with low molecular weight
B Peschke1, M Ankersen, T K Hansen
1Health Care Chemistry, Novo Nordisk A/S, Novo Nordisk Park, 2760, Måløv, Denmark. bpes@novo.dk
European Journal of Medicinal Chemistry
|July 25, 2000
Abstract:
Based on NN703, low molecular weight growth hormone secretagouges (GHSs) with a reduced number of hydrogen binding sites were designed by removal of the C-terminal amide group. The compounds were highly potent in combination with high efficacy in a rat pituitary cell assay, being characterized with EC(50) values down to 0.8 nM. Selected compounds were tested in in vivo animal models. The oral bioavailability in dogs was 16-44%. Also, the ED(50) values of the compounds were determined both in dog and swine.