New highly potent dipeptidic growth hormone secretagogues with low molecular weight

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

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Binding Sites
  • Biological Availability
  • Dipeptides / chemistry*
  • Dipeptides / pharmacology*
  • Dogs
  • Drug Evaluation, Preclinical / methods
  • Female
  • Growth Hormone / drug effects
  • Growth Hormone / metabolism*
  • Hydrogen
  • Male
  • Molecular Mimicry
  • Molecular Weight
  • Pituitary Gland / drug effects
  • Pituitary Gland / metabolism
  • Rats
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology
  • Swine
  • Thiophenes / chemistry*
  • Thiophenes / pharmacology*

Substances

  • 5-methyl-5-(methylamino)-N-methyl-N-(1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)hex-2-enamide
  • Dipeptides
  • Sulfonamides
  • Thiophenes
  • Hydrogen
  • Growth Hormone
  • tabimorelin