Parallel synthesis and pharmacological screening of nonpeptide ligands of the neuropeptide Y receptor subtype Y5.
Several series of low-molecular-mass ligands of the neuropeptide receptor subtype Y5 were prepared using a mixed strategy of synthesis on solid phase and in solution. Collections of single compounds were obtained by an automated parallel procedure which allowed quick variation and investigation of the central spacer moiety, as well as of the aromatic substituents on each side. The strategy of parallel synthesis and screening of partially purified analogs helped to select rapidly potent and selective leads which displayed comparable antagonistic potency against neuropeptide Y activity on the Y5 receptor and better receptor selectivity than the original reference compounds.
Henlin
J M
JM
Institut de Recherches Servier, Suresnes, France; Institut de Recherches Servier, Croissy sur Seine, France.
Boutin
J A
JA
Duchêne-Roger
F
F
Nicolas
J P
JP
Desmet-Beaufort
C
C
Levens
N
N
Fauchère
J L
JL
D000818:Animals; D019556:COS Cells; D008024:Ligands; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism*
D008024:Ligands; D017476:Receptors, Neuropeptide Y