Synthesis of galmic: a nonpeptide galanin receptor agonist

Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16727-32. doi: 10.1073/pnas.0407543101. Epub 2004 Nov 19.

Abstract

Galanin is a neuropeptide with a wide variety of biological functions. Few nonpeptide ligands, capable of activating galanin receptors, are available today. Based on known pharmacophores of galanin and the tripeptidomimetic galnon, a combinatorial library was formulated, synthesized, and screened against the galanin receptor. An active compound, galmic, was identified and tested in vitro and in vivo for its affinity and efficacy at galanin receptors. The present work describes the total synthesis of galmic, the synthesis of its oxazole precursors, the coupling of the building blocks into a linear trimer, and the macrolactamization reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Magnetic Resonance Spectroscopy
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / pharmacology
  • Receptors, Galanin / agonists*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Peptides, Cyclic
  • Receptors, Galanin
  • galmic