1176327-15-3

Upstream product

• 109-86-4 2-methoxy-ethanol 
• 153556-42-4 4-bromo-3-fluorobenzoic acid 

Downstream Products

• 1176327-29-9 tert-butyl 4-[4-chloro-3-(2-methoxyethoxy)benzyl]piperidine-1-carboxylate 
• 1265463-58-8 6-(2-{4-[4-bromo-3-(2-hydroxyethoxy)benzyl]piperidin-1-yl}ethyl)-3-hydroxy-2,3-dihydro-4H-chromen-4-one 
• 1265464-41-2 C₂₇H₃₆BrNO₆ 
• 1234286-77-1 tert-Butyl [2-bromo-5-({1-[2-(4-oxo-3,4-dihydro-2H-chromen-6-yl)ethyl]piperidin-4-yl}methyl)phenoxy]acetate 
• 1265463-92-0 6-{2-[4-(4-Bromo-3-hydroxybenzyl)piperidin-1-yl]ethyl}-3,4-dihydro-2H-chromen-4-ol 
• 1265464-51-4 tert-Butyl [2-bromo-5-({1-[2-(4-oxo-4H-chromen-6-yl)ethyl]piperidin-4-yl}methyl)phenoxy]acetate 
• 1265464-49-0 tert-Butyl [2-bromo-5-({1-[2-(3-hydroxy-4-oxo-3,4-dihydro-2H-chromen-6-yl)ethyl]piperidin-4-yl}methyl)phenoxy]acetate 
• 1265464-47-8 tert-Butyl [2-bromo-5-({1-[2-(3-hydroxy-4,4-dimethoxy-3,4-dihydro-2H-chromen-6-yl)ethyl]piperidin-4-yl}methyl)phenoxy]acetate 
• 1265464-45-6 6-(2-{4-[4-Bromo-3-(methoxymethoxy)benzyl]piperidin-1-yl}ethyl)-4H-chromen-4-one 
• 1265463-70-4 6-{2-[4-(4-Bromo-3-hydroxybenzyl)piperidin-1-yl]ethyl}-2,3-dihydro-4H-chromen-4-one 
• 1265464-43-4 6-(2-{4-[4-Bromo-3-(methoxymethoxy)benzyl]piperidin-1-yl}ethyl)-4,4-dimethoxy-3,4-dihydro-2H-chromen-3-ol 
• 1265463-52-2 6-(2-{4-[4-Bromo-3-(2-hydroxyethoxy)benzyl]piperidin-1-yl}ethyl)-3,4-dihydro-2H-chromen-4-ol 
• 1265463-49-7 6-(2-{4-[4-Bromo-3-(2-methoxyethoxy)benzyl]piperidin-1-yl}ethyl)-3,4-dihydro-2H-chromen-4-ol benzenesulfonate (salt) 
• 1232867-07-0 tert-Butyl 4-[4-bromo-3-(2-tert-butoxy-2-oxoethoxy)benzyl]piperidine-1-carboxylate 

Relevant academic research and scientific papers

Discovery of DSP-1053, a novel benzylpiperidine derivative with potent serotonin transporter inhibitory activity and partial 5-HT1A receptor agonistic activity

We have previously shown that SMP-304, a serotonin uptake inhibitor with weak 5-HT1A partial agonistic activity, may act under high serotonin levels as a 5-HT1A antagonist that improves the onset of paroxetine in the rat swimming test. However, SMP-304 is mostly metabolized by CYP2D6, indicating limited efficacy among individuals and increased side effects. To reduce CYP2D6 metabolic contribution and enhance SERT/5-HT1A binding affinity, we carried out a series of substitutions at the bromine atom in the left part of the benzene ring of SMP-304 and replaced the right part of SMP-304 with a chroman-4-one. This optimization work led to the identification of the antidepressant candidate DSP-1053 as a potent SERT inhibitor with partial 5-HT1A receptor agonistic activity. DSP-1053 showed low CYP2D6 metabolic contribution and a robust increase in serotonin levels in the rat frontal cortex.

A Second Generation Synthesis of Benzyl Piperidine Derivatives: A Key Intermediate for the Preparation of SERT/5-HT1A Dual Inhibitor

A second generation process for benzyl piperidine 10 is described. By the use of a Horner-Wadsworth-Emmons reaction and selective hydrogenation with Pt/C in ethyl acetate, 2-bromo-5-(hydroxymethyl) phenol 14 was efficiently converted to the compound 10 on a 5 kg scale. A small amount of water was found to be critical to complete the selective hydrogenation with low levels of debrominated byproduct 15. Impurities of the compound 10 were controlled by limiting the quality of 2-bromo-5-(hydroxymethyl) phenol 14 and 1-bromo-2-methoxyethane 15.

BENZYL PIPERIDINE COMPOUND

Provided is a new serotonin-reuptake inhibitor that exhibits affinity for serotonin-1A receptors. Said serotonin-reuptake inhibitor is a compound represented by formula (1) or a pharmacologically acceptable salt thereof. In the formula, R1 represents a hydrogen atom, a 2-hydroxyethyl group, or a 2-methoxyethyl group. R2 represents one of the following bonded to a methylene group which is bonded to a piperidine ring: a chlorine atom bonded in a p-position; a bromine atom bonded in a p-position; a methyl group bonded in a p-position; a chlorine atom bonded in an m-position; or a bromine atom bonded in an m-position. Either Y1 represents a hydrogen atom and Y2 represents a hydrogen atom or a hydroxyl group, or Y1 and Y2 together represent an oxo group. Z represents a group represented by one of the following formulas: formula (3-1-1), formula (3-1-2), formula (3-2-1), formula (3-2-2), formula (3-3-1), formula (3-3-2), formula (3-4-1), or formula (3-4-2). However, if R1 represents a 2-hydroxyethyl group or a 2-methoxyethyl group and Y1 and Y2 both simultaneously represent hydrogen atoms, then Z represents a group represented by one of the following formulas: formula (3-1-2), formula (3-2-1), formula (3-2-2), formula (3-3-1), formula (3-3-2), formula (3-4-1), or formula (3-4-2).

BENZYLPIPERIZINE COMPOUND

Disclosed is a benzylpiperizine compound represented by formula (1) or a pharmaceutically acceptable salt thereof, which is useful as a medicinal agent such as an antidepressant agent. (In the formula (1), R1 represents a hydrogen atom or a met