87289-71-2Relevant academic research and scientific papers
Nitrile analogs of meperidine as high affinity and selective sigma-1 receptor ligands
Mercer, Susan L.,Shaikh, Jamaluddin,Traynor, John R.,Matsumoto, Rae R.,Coop, Andrew
, p. 1304 - 1308 (2008/09/21)
A series of N-substituted-4-cyano-4-phenylpiperidine analogs were synthesized and evaluated for binding affinity at opioid receptors and showed no affinity. The series similarity to previously reported σ ligands prompted analysis at σ receptors to determine the SAR for affinity at σ receptors. Within the N-substituent series the saturated analogs showed increased affinity at both σ receptors. Optimal chain length in the N-arylalkyl series for σ1 and σ2 receptors proved to be N-propylphenyl; extension to a four carbon chain dramatically decreased affinity at both receptors. Substituents in the 4-position affect only σ1 affinity; no change in affinity at σ2 was shown. The N-isobutyl, N-phenylpropyl, and N-benzyl analogs are worth pursuing due to their good affinity and selectivity at the σ1 receptor, whereas the N-benzyl analog exhibits the greatest selectivity for σ1.
Opioids and efflux transporters. Part 1: P-Glycoprotein substrate activity of N-substituted analogs of meperidine
Mercer, Susan L.,Hassan, Hazem E.,Cunningham, Christopher W.,Eddington, Natalie D.,Coop, Andrew
, p. 1160 - 1162 (2007/10/03)
P-Glycoprotein (P-gp) is an efflux transporter which is up-regulated at the blood-brain barrier in both morphine- and oxycodone-tolerant rats. Numerous studies have shown that many clinically employed opioid analgesics are substrates for P-gp, suggesting that up-regulation of P-gp may contribute to the development of central tolerance to opioids. The studies herein focus on the development of SAR for P-gp substrate activity in the meperidine series of compounds, and show that a meperidine analog of greater potency, N-phenylbutyl-N-normeperidine, has low activity as a P-gp substrate and has the potential to be utilized as a tool to study the contribution of P-gp to the development of central tolerance to opioids.
Facile Synthesis of N-Substituted-4-cyano-4-phenylpiperidines via Phase-Transfer Catalysis
Thompson, Doug,Reeves, Perry C.
, p. 771 - 772 (2007/10/02)
Phenylacetonitrile can be condensed with N-substituted-bis(2-chloroethyl)amines in aqueous sodium hydroxide solution to produce N-substituted-4-cyano-4-phenylpiperidines.Hexadecyltributylphosphonium bromide is an effective catalyst for this phase-transfer reaction.
