新型高效、低分子量的二肽类生长激素促分泌素

New highly potent dipeptidic growth hormone secretagogues with low molecular weight.

作者信息

Peschke B, Ankersen M, Hansen T K, Hansen B S, Lau J, Nielsen K K, Raun K

机构信息

Health Care Chemistry, Novo Nordisk A/S, Novo Nordisk Park, 2760, Måløv, Denmark.

出版信息

Eur J Med Chem. 2000 Jun;35(6):599-618. doi: 10.1016/s0223-5234(00)00160-4.

DOI:10.1016/s0223-5234(00)00160-4

PMID:10906412

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.

摘要

基于NN703，通过去除C末端酰胺基团设计了具有减少数量氢键结合位点的低分子量生长激素促分泌素（GHSs）。这些化合物在大鼠垂体细胞试验中具有高效结合的高活性，其特征在于EC(50)值低至0.8 nM。选择的化合物在体内动物模型中进行了测试。在犬中的口服生物利用度为16 - 44%。此外，还测定了这些化合物在犬和猪中的ED(50)值。