Derivatives of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl-p-iodobenzamido)ethyl]pipera zine (p-MPPI) as 5-HT1A ligands.

A series of new p-alkylbenzamido derivatives of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p- iodobenzamido)ethyl]piperazines (p-MPPI) were prepared. In vitro binding studies suggest that p-methyl and p-ethyl substituents on the benzamido group display the same high binding affinity to 5-HT1A receptors (Ki = 2.2 and 9.3 nM, rat hippocampal homogenates). However, when the substitution groups were larger than a C5 pentyl group, the affinity to 5-HT1A receptors dropped below a useful level (Ki > 50 nM). Several irreversible binding agents (CH2Cl, NHCOCH2Cl) and a photoaffinity labeling compound (m-iodo p-azido) which showed good binding affinity to 5-HT1A receptors were successfully prepared.