Structure-activity relationship studies of CNS agents, XIX: Quantitative analysis of the alkyl chain effects on the 5-HT(1A) and 5-HT2 receptor affinities of 4-alkyl-1-arylpiperazines and their analogs

Article abstract of DOI:10.1002/ardp.19953280210

The 5-HT(1A) 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-HT(1A) ligands of all the investigated N-alkyl homologues. The alkyl chain may stablize the 5-HT(1A) receptor-ligand complex by hydrophobic forces. A set of the alkyl substituent contributions (C(HT1A)) for prediction of the 5-HT(1A) affinity of N-alkyl derivatives of 1-arylpiperazines and related compounds have been defined on the basis of the Free-Wilson analysis.