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.
B L Palucki  1 ,  S D Feighner ,  S Pong ,  K K McKee ,  D L Hreniuk ,  C Tan ,  A D Howard ,  L H Van der Ploeg ,  A A Patchett ,  R P Nargund
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, 07065, Rahway, NJ, USA. [email protected]
PMID: 11459669 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.