Parallel synthesis and pharmacological screening oi nonpeptide ligands of the neuropeptide Y receptor subtype Y-5

Several series of low-molecular-mass ligands of the neuropeptide receptor s ubtype Y5 were prepared using a mixed strategy of synthesis on solid phase and in solution. Collections of single compounds were obtained by an automa ted parallel procedure which allowed quick variation and investigation of t he central spacer moiety, as well as of the aromatic substituents on each s ide. The strategy of parallel synthesis and screening of partially purified analogs helped to select rapidly potent and selective leads which displaye d comparable antagonistic potency against neuropeptide Y activity on the Y5 receptor and better receptor selectivity than the original reference compo unds.