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

William Nguyen, Brittany Louise Howard, David Jenkins, Heike Wulff, Philip Thompson, David Thomas Manallack

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12 Citations (Scopus)


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. (C) 2012 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)7106 - 7109
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number23
Publication statusPublished - 2012

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