STRUCTURE-ACTIVITY RELATIONSHIP STUDIES OF CNS AGENTS .24. NEW ANALOGS OF YL)-1-PIPERAXINYL]-2-PHENYLPROPANAMIDE(WAY-100135)

A series of new N-substituted derivatives of methoxyphenyl)-1-piperazi nyl]-2-phenylpropanamide, 6-10, were synthesized and their 5-HT1A, 5-H T2A, and alpha(1) receptor affinities were determined. All the compoun ds were highly potent 5-HT1A ligands with a moderate or low 5-HT2A and alpha(1) affinity. It was shown that the 5-HT2A affinity of 1 and 6-1 0 depended crucially on the volume of amide substituents. None of the investigated racemic mixtures 1 and 6-8 antagonized the 8-OH-DPAT-indu ced lower lip retraction in rats, whereas (+/-)-7 behaved like a weak agonist of 5-HT1A receptors in the model used.