TY - JOUR
T1 - Structure-activity relationship exploration of Kv1.3 blockers based on diphenoxylate
AU - Nguyen, William
AU - Howard, Brittany Louise
AU - Jenkins, David
AU - Wulff, Heike
AU - Thompson, Philip
AU - Manallack, David Thomas
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
UR - http://www.journals.elsevier.com/bioorganic-and-medicinal-chemistry-letters/#description
U2 - 10.1016/j.bmcl.2012.09.080
DO - 10.1016/j.bmcl.2012.09.080
M3 - Article
SN - 0960-894X
VL - 22
SP - 7106
EP - 7109
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 23
ER -