STRUCTURE-ACTIVITY RELATIONSHIP STUDIES OF CNS AGENTS .19. QUANTITATIVE-ANALYSIS OF THE ALKYL CHAIN EFFECTS ON THE 5-HT1A AND 5-HT2 RECEPTOR AFFINITIES OF 4-ALKYL-1-ARYLPIPERAZINES AND THEIR ANALOGS

The 5-HT1A and 5-HT2 receptor affinity of a set of 44 N-alkylated 1-arylpiperazines and their analogs has been analyzed: the n-hexyl derivatives were the most potent and the most selective 5-HT1A ligands of all the investigated N-alkyl homologues. The alkyl chain may stabilize the 5-HT1A receptor-ligand complex by hydrophobic forces. A set of the alkyl substituent contributions (C-HT1A) for prediction of the 5-HT1A affinity of N-alkyl derivatives of 1-arylpiperazines and related compounds have been defined on the basis of the Free-Wilson analysis.