New active series of growth hormone secretagogues

J Med Chem. 2003 Mar 27;46(7):1191-203. doi: 10.1021/jm020985q.

Abstract

New growth hormone secretagogue (GHS) analogues were synthesized and evaluated for growth hormone releasing activity. This series derived from EP-51389 is based on a gem-diamino structure. Compounds that exhibited higher in vivo GH-releasing potency than hexarelin in rat (subcutaneous administration) were then tested per os in beagle dogs and for their binding affinity to human pituitary GHS receptors and to hGHS-R 1a. Compound 7 (JMV 1843, H-Aib-(d)-Trp-(d)-gTrp-formyl) showed high potency in these tests and was selected for clinical studies.(1)

MeSH terms

  • Administration, Oral
  • Adult
  • Animals
  • Animals, Newborn
  • Binding, Competitive
  • Cell Line
  • Dogs
  • Female
  • Growth Hormone / metabolism*
  • Humans
  • In Vitro Techniques
  • Indoles
  • Injections, Subcutaneous
  • Male
  • Membranes
  • Middle Aged
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Pituitary Gland / metabolism
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / metabolism
  • Receptors, G-Protein-Coupled*
  • Receptors, Ghrelin
  • Tryptophan / analogs & derivatives

Substances

  • Indoles
  • Oligopeptides
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Ghrelin
  • macimorelin
  • Tryptophan
  • Growth Hormone