The computer-aided discovery of novel family of the 5-HT6 serotonin receptor ligands among derivatives of 4-benzyl-1,3,5-triazine

Add time:07/12/2019    Source:sciencedirect.com

The work describes a discovery of new chemical family of potent ligands for the 5-HT6 serotonin receptors. During the search for new histamine H4 receptor antagonists among 1,3,5-triazine derivatives, compound 2 (4-benzyl-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine) was found. Compound 2, weakly active for the H4 receptor but fitted in 3/4 of pharmacophore features of the 5-HT6R ligand, occurred to be a moderate 5-HT6R agent, useful as a lead structure for further modifications. A series of new derivatives (3–19) of the lead 2 was synthesized, evaluated in the radioligand binding assay (RBA) and explored in comprehensive molecular modelling, including both pharmacophore- and structure-based approaches with docking to the homology model of 5-HT6R. The most active compounds displayed a potent affinity for the 5-HT6R in the nanomolar range (Ki = 20–30 nM), some of them (4, 11 and 19) were tested in the rat forced swim test that revealed their antidepressant-like effect. SAR-analysis on the basis of both, RBA and docking results, indicated that action on the receptor is related to the hydrophobicity and the size of aromatic moiety substituted by a methylene linker at the position 4 of 1,3,5-triazine.

We also recommend Trading Suppliers and Manufacturers of N-(4-{[benzyl(methyl)amino]sulfonyl}phenyl)-2-bromobenzamide (cas 497090-02-5). Pls Click Website Link as below: cas 497090-02-5 suppliers

Prev:Synthesis, evaluation and CoMFA/CoMSIA study of nitrofuranyl methyl N-heterocycles as novel antitubercular agents
Next:Design, synthesis and bioevaluation of 2-mercapto-6-phenylpyrimidine-4-carboxylic acid derivatives as potent xanthine oxidase inhibitors)