AI Article Synopsis
- A new family of melatonin receptor ligands was developed by modifying the pharmacokinetic properties of Agomelatine, introducing quinazoline and phthalazine scaffolds with specific chemical groups.
- The biological activity of the newly synthesized ligands showed that they could achieve strong binding affinity, particularly as potent agonists, when compared to Agomelatine.
- While the inclusion of two nitrogen atoms led to a decrease in receptor affinity, these compounds still demonstrated favorable pharmacokinetic properties, indicating potential for further development.
Article Abstract
For further development of successors of Agomelatine through modulation of its pharmacokinetic properties, we report herein the design, synthesis and pharmacological results of a new family of melatonin receptor ligands. Issued from the introduction of quinazoline and phthalazine scaffolds carrying an ethyl amide lateral chain and a methoxy group as bioisosteric ligands analogues of previously developed Agomelatine. The biological activity of the prepared analogues was compared with that of Agomelatine. Quinazoline and phthalazine rings proved to be a versatile scaffold for easy feasible MT and MT ligands. Potent agonists with sub-micromolar binding affinity were obtained. However, the presence of two nitrogen atoms resulted in compounds with lower affinity for both MT and MT, in comparison with the parent compound, balanced by the exhibition of good pharmacokinetic properties.
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| http://dx.doi.org/10.1016/j.ejmech.2020.112078 | DOI Listing |
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