1198318-49-8Relevant articles and documents
Synthesis of novel pyrido[1,2-c]pyrimidine derivatives with 6-fluoro-3-(4-piperidynyl)-1,2-benzisoxazole moiety as potential ssri and 5-ht1a receptor ligands
Król, Marek,?lifirski, Grzegorz,Kleps, Jerzy,Ulenberg, Szymon,Belka, Mariusz,Baczek, Tomasz,Siwek, Agata,Stachowicz, Katarzyna,Szewczyk, Bernadeta,Nowak, Gabriel,Duszyńska, Beata,Herold, Franciszek
, p. 1 - 21 (2021/03/01)
Two series of novel 4-aryl-2H-pyrido[1,2-c]pyrimidine (6a–i) and 4-aryl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidine (7a–i) derivatives were synthesized. The chemical structures of the new compounds were confirmed by1H and13C NMR spectroscopy and ESI-HRMS spectrome-try. The affinities of all compounds for the 5-HT1A receptor and serotonin transporter protein (SERT) were determined by in vitro radioligand binding assays. The test compounds demonstrated very high binding affinities for the 5-HT1A receptor of all derivatives in the series (6a–i and 7a–i) and generally low binding affinities for the SERT protein, with the exception of compounds 6a and 7g. Extended affinity tests for the receptors D2, 5-HT2A, 5-HT6 and 5-HT7 were conducted with regard to selected compounds (6a, 7g, 6d and 7i). All four compounds demonstrated very high affinities for the D2 and 5-HT2A receptors. Compounds 6a and 7g also had high affinities for 5-HT7, while 6d and 7i held moderate affinities for this receptor. Compounds 6a and 7g were also tested in vivo to identify their functional activity profiles with regard to the 5-HT1A receptor, with 6a demonstrating the activity profile of a presynaptic agonist. Metabolic stability tests were also conducted for 6a and 6d.
Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT1A activity. part 5
Gomolka, Anna,Ciesielska, Agnieszka,Wróbel, Martyna Z.,Chodkowski, Andrzej,Kleps, Jerzy,Dawidowski, MacIej,Siwek, Agata,Wolak, Malgorzata,Stachowicz, Katarzyna,Slawinska, Anna,Nowak, Gabriel,Satala, Grzegorz,Bojarski, Andrzej J.,Belka, Mariusz,Ulenberg, Szymon,Baczek, Tomasz,Skowronek, Pawel,Turlo, Jadwiga,Herold, Franciszek
, p. 221 - 236 (2015/06/08)
A series of novel 4-aryl-pyrido[1,2-c]pyrimidine derivatives containing a 1-(2-quinoline)piperazine moiety was synthesized. The chemical structure of new compounds was confirmed by FT-IR, 1H NMR, 13C NMR and HRMS spectra as well as elemental analysis. Affinity of the novel pyrido[1,2-c]pyrimidine derivatives for 5-HT1A, 5-HT2A receptors and serotonin transporter (SERT) was evaluated in an in vitro radioligand binding assay. Tested compounds showed moderate to high affinity for 5-HT1AR and SERT and low affinity for 5-HT2AR. Selected ligands were subjected to in vivo tests, such as induced hypothermia and the forced swimming test in mice, which determined presynaptic agonistic activity of the ligands 8d, 8e, 9d and 9e and presynaptic antagonistic activity of the ligands 8a, 8b, 9a, 9b. Additionally, metabolic stability evaluation was performed for selected ligands, proving that a para-substitution in the 4-aryl-pyrido[1,2-c]pyrimidine moiety leads to an increase in stability, whereas a substitution in the ortho-position lowers the stability.
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.
