256504-41-3

Upstream product

• 619-66-9 4-Carboxybenzaldehyde 
• 186094-07-5 4-(Phenyl-hydroxymethyl)-N,N-diethylbenzamide 
• 58287-77-7 N,N-diethyl-4-formylbenzamide 
• 110-85-0 piperazine 
• 186094-11-1 4-(Chloro-phenyl-methyl)-N,N-diethylbenzamide 

Downstream Products

• 193217-37-7 4-[[4-(tert-butoxycarbonyl)-1-piperazinyl](phenyl)methyl]benzoic acid 
• 193217-01-5 4-[[4-(tert-butoxycarbonyl)-1-piperazinyl](phenyl)methyl]benzoic acid methyl ester 
• 308110-05-6 4-(phenyl-piperazin-1-yl-methyl)-benzonitrile 

Relevant academic research and scientific papers

New diarylmethylpiperazines as potent and selective nonpeptidic δ opioid receptor agonists with increased in vitro metabolic stability

Nonpeptide δ opioid agonists are analgesics with a potentially improved side-effect and abuse liability profile, compared to classical opioids. Andrews analysis of the NIH nonpeptide lead SNC-80 suggested the removal of substituents not predicted to contribute to binding. This approach led to a simplified lead, N,N-diethyl-4-[phenyl(1-piperazinyl)methyl]benzamide (1), which retained potent binding affinity and selectivity to the human δ receptor (IC50 = 11 nM, μ/δ = 740, κ/δ > 900) and potency as a full agonist (EC50 = 36 nM) but had a markedly reduced molecular weight, only one chiral center, and increased in vitro metabolic stability. From this lead, the key pharmacophore groups for δ receptor affinity and activation were more clearly defined by SAR and mutagenesis studies. Further structural modifications on the basis of 1 confirmed the importance of the N,N-diethylbenzamide group and the piperazine lower basic nitrogen for δ binding, in agreement with mutagenesis data. A number of piperazine N-alkyl substituents were tolerated. In contrast, modifications of the phenyl group led to the discovery of a series of diarylmethylpiperazines exemplified by N,N-diethyl-4-[1-piperazinyl(8-quinolinyl)-methyl]benzamide (56) which had an improved in vitro binding profile (IC50 = 0.5 nM, μ/δ = 1239, EC50 = 3.6 nM) and increased in vitro metabolic stability compared to SNC-80.

Probes for narcotic receptor mediated phenomena. 26. Synthesis and biological evaluation of diarylmethylpiperazines and diarylmethylpiperidines as novel, nonpeptidic δ opioid receptor ligands

We recently reported (+)-4-[(αR)-α-{(2S,5R)-4-allyl-2,5- dimethyl-1-piperazinyl}-3-methoxybenzyl]-N,N-diethylbenzamide (1b, SNC80) as a novel nonpeptidic δ receptor agonist and explored the structure-activity relationships (SAR) of a series of related der