Referenced in: none

Automatically associated channels: Kv1.3

Title: Structure-activity relationship exploration of Kv1.3 blockers based on diphenoxylate.

Authors: William Nguyen, Brittany L Howard, David P Jenkins, Heike Wulff, Philip E Thompson, David T Manallack

Journal, date & volume: Bioorg. Med. Chem. Lett., 2012 Dec 1 , 22, 7106-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23084278

Abstract
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 IC(50) values.