Design and synthesis of new potent 5-HT 7 receptor ligands as a candidate for the treatment of central nervous system diseases

Owing to their multifunctional pharmacological profiles (including dual 5-HT /5-HT action), arylpiperazine derivatives are widely used for treating central nervous system diseases including the depression or neuropathic pain. Herein we describe the design, synthesis and evaluation of biological acti...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2022-01, Vol.227, p.113931
Main Authors: Kułaga, Damian, Drabczyk, Anna K, Satała, Grzegorz, Latacz, Gniewomir, Rózga, Karolina, Plażuk, Damian, Jaśkowska, Jolanta
Format: Article
Language:English
Subjects:
Cell Proliferation - drug effects
Cell Survival - drug effects
Central Nervous System Diseases - drug therapy
Central Nervous System Diseases - metabolism
Dose-Response Relationship, Drug
Drug Design
Hep G2 Cells
Humans
Ligands
Models, Molecular
Molecular Structure
Receptors, Serotonin - metabolism
Structure-Activity Relationship
Triazines - chemical synthesis
Triazines - chemistry
Triazines - pharmacology
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Summary:Owing to their multifunctional pharmacological profiles (including dual 5-HT /5-HT action), arylpiperazine derivatives are widely used for treating central nervous system diseases including the depression or neuropathic pain. Herein we describe the design, synthesis and evaluation of biological activity of novel 5-HT ligands derived of 2,4,6-triamino-1,3,5-triazine. The studied compounds showed affinity and high selectively towards 5-HT receptor with the two most active compounds 34 (K  = 61 nM), 22 (K  = 109 nM) showing good metabolic stability and moderate affinity to CYP3A4 isoenzyme. Compound 22 had high hepatotoxicity at a concentration below 50 μM, while compound 34 showed low hepatotoxicity even at a concentration above 50 μM.
ISSN:1768-3254