Design, Synthesis and Biological Evaluation of Novel 1,3,5-Triazines: Effect of Aromatic Ring Decoration on Affinity to 5-HT<sub>7</sub> Receptor
Considering the key functions of the 5-HT<sub>7</sub> receptor, especially in psychiatry, and the fact that effective and selective 5-HT<sub>7</sub> receptor ligands are yet to be available, in this work, we designed and synthesized novel 1,3,5-triazine derivatives particular...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/21/13308 |
| Summary: | Considering the key functions of the 5-HT<sub>7</sub> receptor, especially in psychiatry, and the fact that effective and selective 5-HT<sub>7</sub> receptor ligands are yet to be available, in this work, we designed and synthesized novel 1,3,5-triazine derivatives particularly based on the evaluation of the effect of substituents at aromatic rings on biological activity. The tested compounds showed high affinity to the 5-HT<sub>7</sub> receptor, particularly ligands N<sup>2</sup>-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N<sup>4</sup>-phenethyl-1,3,5-triazine-2,4,6-triamine <b>2</b> (<i>K</i><sub>i</sub> = 8 nM) and N<sup>2</sup>-(2-(1H-indol-3-yl)ethyl)-N<sup>4</sup>-(2-((4-fluorophenyl)amino)ethyl)-1,3,5-triazine-2,4,6-triamine <b>12</b> (<i>K</i><sub>i</sub> = 18 nM) which showed moderate metabolic stability, and affinity to the CYP3A4 isoenzyme. As for the hepatotoxicity evaluation, the tested compounds showed moderate cytotoxicity only at concentrations above 50 µM. Compound <b>12</b> exhibited less cardiotoxic effect than <b>2</b> on Danio rerio in vivo model. |
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| ISSN: | 1661-6596 1422-0067 |