1198318-40-9Relevant academic research and scientific papers
Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT1A activity: Part 2
Herold, Franciszek,Izbicki, Lukasz,Chodkowski, Andrzej,Dawidowski, Maciej,Krol, Marek,Kleps, Jerzy,Turlo, Jadwiga,Wolska, Irena,Nowak, Gabriel,Stachowicz, Katarzyna,Dybala, Malgorzata,Siwek, Agata,Nowak, Mateusz,Pieniazek, Elzbieta,Jaronczyk, Malgorzata,Sylte, Ingebrigt,Mazurek, Aleksander P.
experimental part, p. 4702 - 4715 (2009/12/28)
Derivatives of 4-aryl-5,6,7,8-tetrahydro-pyrido[1,2-c]pyrimidine were synthesized. These compounds contain the 3-(4-piperidyl)-1H-indole residue or its 5-methoxy or 2-methyl derivative. In vitro binding tests were performed to determine the affinity of the compounds for the 5-HT1A receptor and serotonin transporter (SERT) proteins in the rat brain cortex. In vivo studies, particularly the inducible hypothermia test and forced swimming test, were conducted to determine agonistic/antagonistic activity with pre- and postsynaptic 5-HT1A receptors. Molecular modeling techniques were used to determine the binding modes of the selected compounds at the 5-HT1A receptor and SERT. The SAR analysis showed that the presence of the 3-(4-piperidyl)-1H-indole group or its 5-methoxy derivative, as well as a para substitution with -OCH3 or -F in the aryl ring of 4-aryl-5,6,7,8-tetrahydro-pyrido[1,2-c]pyrimidine, results in an increased affinity for both the 5-HT1A receptors and SERT. In contrast, the presence of the 2-methyl-3-(4-piperidyl)-1H-indole group resulted in a considerable decrease in binding affinity.
