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Herold F, Chodkowski A, Izbicki L, Krol M, Kleps J, Turlo J, Nowak G, Stachowicz K, Dybala M, Siwek A: Novel 4-aryl-pyrido [1,2-c] pyrimidines with dual SSRI and 5-HT1A activity, part 1. Eur J Med Chem. 2009 Apr;44(4):1710-7. Epub 2008 Sep 30.
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. |
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