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 _1A /5-HT ₇ 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 ₇ ligands derived of 2,4,6-triamino-1,3,5-triazine. The studied compounds showed affinity and high selectively towards 5-HT ₇ receptor with the two most active compounds 34 (K _i  = 61 nM), 22 (K _i  = 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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