A series of new derivatives of 4-aryl-pyrido[1,2-c]
pyrimidine containing the 3-(4-piperidyl)-1H-indole residue or its 5-methoxy derivative were synthesized. They were characterized (i) in vitro by binding to
5-HT(1A) receptors and
5-HT transporter proteins in rat
brain cortex membranes and (ii) in vivo in
the mouse by induced
hypothermia and forced swimming models for antagonist/
agonist activity against the
5-HT(1A)
autoreceptors and
postsynaptic 5-HT(1A) receptors, respectively.
Structure activity relationship evaluation indicated that the presence of the 3-(4-piperidyl)-1H-indole residue and ortho- or para-substituents with -F or -CH(3) groups in the
aryl ring as well as an unsubstituted
aryl in the 4-aryl-pyrido[1,2-c]
pyrimidine moiety promoted low K(i) values for both receptors. In contrast, the presence of a 5-methoxy-3-(4-piperidyl)-1H-indole residue as well as -Cl or -OCH(3)
substituents at the para position markedly reduced the
receptor affinity.
