Spiro(indoline-3,4'-piperidine) growth hormone secretagogues as ghrelin mimetics

Bioorg Med Chem Lett. 2001 Jul 23;11(14):1955-7. doi: 10.1016/s0960-894x(01)00324-9.

Abstract

A series of small molecules derived from MK-0677, a potent synthetic GHS, mimicking the N-terminal Gly-Ser-O-(n-octanoyl)-L-Ser-Phe segment of ghrelin was synthesized and tested in a binding and in a functional assay measuring intracellular calcium elevation in HEK-293 cells expressing hGHSR1a. Replacement of Phe in this tetrapeptide with a spiro(indoline-3,4'-piperidine) group, Gly-Ser with 2-aminoisobutyric acid, and O-(n-octanoyl)-L-Ser with O-benzyl-D-Ser provided synthetic GHS agonists with similar functional potency as ghrelin.

MeSH terms

  • Binding Sites / physiology
  • Calcium / metabolism*
  • Cells, Cultured
  • Ghrelin
  • Humans
  • Indoles / chemistry
  • Indoles / metabolism*
  • Inhibitory Concentration 50
  • Luminescence
  • Molecular Mimicry
  • Peptide Hormones*
  • Peptides / chemistry
  • Peptides / metabolism*
  • Piperidines / chemical synthesis
  • Piperidines / metabolism*
  • Protein Binding / physiology
  • Receptors, Cell Surface / metabolism*
  • Receptors, G-Protein-Coupled*
  • Receptors, Ghrelin
  • Spiro Compounds / chemistry
  • Spiro Compounds / metabolism*

Substances

  • Ghrelin
  • Indoles
  • Peptide Hormones
  • Peptides
  • Piperidines
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Ghrelin
  • Spiro Compounds
  • piperidine
  • ibutamoren mesylate
  • Calcium