149669-43-2Relevant articles and documents
Synthesis and biological evaluation of new multi-target 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives with potential antidepressant effect
Wróbel, Martyna Z.,Chodkowski, Andrzej,Herold, Franciszek,Marciniak, Monika,Dawidowski, Maciej,Siwek, Agata,Starowicz, Gabriela,Stachowicz, Katarzyna,Szewczyk, Bernadeta,Nowak, Gabriel,Belka, Mariusz,B?czek, Tomasz,Sata?a, Grzegorz,Bojarski, Andrzej J.,Tur?o, Jadwiga
, (2019)
A series of novel 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives were synthesised and evaluated for their 5-HT1A/D2/5-HT2A/5-HT6/5-HT7 receptor affinity and serotonin reuptake inhibition. Most of the evaluated compounds displayed high affinities for 5-HT1A receptors (e.g., 4c Ki = 2.3 nM, 4l Ki = 3.2 nM). The antidepressant activity of the selected compounds was screened in vivo using the forced swim test (FST). The results indicate that compound MW005 (agonist of the pre- and postsynaptic 5-HT1A receptor) exhibited promising affinities for the 5-HT1A/SERT/D2/5-HT6/5-HT7 receptors and showed an antidepressant-like activity in the FST model.
Substituted heterocyclic compounds and application of same to medicines
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Paragraph 0201; 0211; 0212; 0213; 0214, 0286; 0287-0289, (2017/04/29)
The invention relates to substituted heterocyclic compounds and application of the same to medicines and specifically provides the novel substituted heterocyclic compounds or stereoisomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof, and preparation methods thereof. The invention also relates to pharmaceutical compositions containing the compounds and application of the compounds or pharmaceutical compositions to treatment of diseases related to 5-HT6 receptors, especially Alzheimer's disease.
Novel 4-aryl-pyrido[1,2-c ]pyrimidines with dual SSRI and 5-HT1A activity. Part 4
Chodkowski, Andrzej,Wróbel, Martyna Z.,Turlo, Jadwiga,Kleps, Jerzy,Siwek, Agata,Nowak, Gabriel,Belka, Mariusz,Baczek, Tomasz,Mazurek, Aleksander P.,Herold, Franciszek
, p. 21 - 32 (2015/01/08)
This project describes the synthesis, pharmacological and pharmacodynamic tests on two series of novel derivatives of 2H-pyrido[1,2-c]pyrimidine with potential binary binding to 5-HT1A receptors and SSRI + serotonin transporters. The influence of piperidinyl-indole (8.1-8.7) and tetrahydropyridinyl-indole (8.8-8.32) residues and indole 5-position substituents (R3 Combining double low line Br, Cl, F) present in the pharmacophore element of ligands on their binding to both molecular targets was tested.A considerable impact of piperidinyl-indole residue on binding to both targets was confirmed and compounds with a high binding affinity were identified: Ki 5-HT1A Combining double low line 12.4 nM; Ki SERT Combining double low line 15.6 nM 8.1; Ki 5-HT1A Combining double low line 5.6 nM; Ki SERT Combining double low line 20.7 nM 8.7, while the presence of a tetrahydropyridinyl-indole residue was found to reduce the affinity of ligands to 5-HT1AR. The presence of chlorine (R3) in this series resulted in a notable reduction in binding to both targets (5-HT1A and SERT). Selected compounds had their metabolic stability in a first-pass test (human liver microsomes, NADPH) determined in vitro, and R1 and R2 substituents present on the terminal residue of pyrido[1,2-c]pyrimidine were recognized as having an impact on stability.