Synthesis of galmic: a nonpeptide galanin receptor agonist.
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.
Ceide
Susana Conde
SC
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Trembleau
Laurent
L
Haberhauer
Gebhard
G
Somogyi
Laszlo
L
Lu
Xiaoying
X
Bartfai
Tamas
T
Rebek
Julius
J
D009682:Magnetic Resonance Spectroscopy; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D044088:Receptors, Galanin / Q000819:agonists*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D010456:Peptides, Cyclic; D044088:Receptors, Galanin; C488574:galmic