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

doi:10.1016/j.bmcl.2012.09.080

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

Medicinal Chemistry

Research output: Contribution to journal › Article › Research › peer-review

7 Citations (Scopus)

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 IC50 values. (C) 2012 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	7106 - 7109
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	23
DOIs	https://doi.org/10.1016/j.bmcl.2012.09.080
Publication status	Published - 2012

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10.1016/j.bmcl.2012.09.080

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Cite this

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title = "Structure-activity relationship exploration of Kv1.3 blockers based on diphenoxylate",

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 IC50 values. (C) 2012 Elsevier Ltd. All rights reserved.",

author = "William Nguyen and Howard, {Brittany Louise} and David Jenkins and Heike Wulff and Philip Thompson and Manallack, {David Thomas}",

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Structure-activity relationship exploration of Kv1.3 blockers based on diphenoxylate. / Nguyen, William; Howard, Brittany Louise; Jenkins, David; Wulff, Heike; Thompson, Philip; Manallack, David Thomas.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 23, 2012, p. 7106 - 7109.

Research output: Contribution to journal › Article › Research › peer-review

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AU - Wulff, Heike

AU - Thompson, Philip

AU - Manallack, David Thomas

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