Discovery of SMP-304, a novel benzylpiperidine derivative with serotonin transporter inhibitory activity and 5-HT1A weak partial agonistic activity showing the antidepressant-like effect

Add time:07/13/2019    Source:sciencedirect.com

We report the discovery of a novel benzylpiperidine derivative with serotonin transporter (SERT) inhibitory activity and 5-HT1A receptor weak partial agonistic activity showing the antidepressant-like effect. The 3-methoxyphenyl group and the phenethyl group of compound 1, which has weak SERT binding activity, but potent 5-HT1A binding activity, were optimized, leading to compound 35 with potent and balanced dual SERT and 5-HT1A binding activity, but also potent CYP2D6 inhibitory activity. Replacement of the methoxy group in the left part of compound 35 with a larger alkoxy group, such as ethoxy, isopropoxy or methoxy-ethoxy group ameliorated CYP2D6 inhibition, giving SMP-304 as a candidate. SMP-304 with serotonin uptake inhibitory activity and 5-HT1A weak partial agonistic activity, which could work as a 5-HT1A antagonist, displayed faster onset of antidepressant-like effect than a representative SSRI paroxetine in an animal model.

We also recommend Trading Suppliers and Manufacturers of 2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)-N,N-dimethylethanaminium chloride (cas 2906-72-1). Pls Click Website Link as below: cas 2906-72-1 suppliers

Prev:Intramolecular ring rearrangements in the mass spectrometric fragmentation of 1-(N-ethoxycarbonylamino)arylmethylphosphonic monoesters under electrospray ionization conditions
Next:Efficient synthesis of 2- and 3-substituted-2,3-dihydro [1,4]dioxino[2,3-b]pyridine derivatives)