102762-46-9Relevant academic research and scientific papers
Structure-activity relationship exploration of Kv1.3 blockers based on diphenoxylate
Nguyen, William,Howard, Brittany L.,Jenkins, David P.,Wulff, Heike,Thompson, Philip E.,Manallack, David T.
supporting information, p. 7106 - 7109 (2013/01/15)
Diphenoxylate, a well-known opioid agonist and anti-diarrhoeal agent, was recently found to block Kv1.3 potassium channels, which have been proposed as potential therapeutic targets for a range of autoimmune diseases. The molecular basis for this Kv1.3 blockade was assessed by the selective removal of functional groups from the structure of diphenoxylate as well as a number of other structural variations. Removal of the nitrile functional group and replacement of the C-4 piperidinyl substituents resulted in several compounds with submicromolar IC50 values.
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.
