The discovery of a potent Nav1.3 inhibitor with good oral pharmacokinetics

In this article, we describe the discovery of an aryl ether series of potent and selective Nav1.3 inhibitors. Based on structural analogy to a similar series of compounds we have previously shown bind to the domain IV voltage sensor region of Nav channels, we propose this series binds in the same lo...

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Published in:MedChemComm 2017-06, Vol.8 (6), p.1255-1267
Main Authors: Pryde, D C, Swain, NA, Stupple, P A, West, C W, Marron, B, Markworth, C J, Printzenhoff, D, Lin, Z, Cox, P J, Suzuki, R, McMurray, S, Waldron, G J, Payne, CE, Warmus, J S, Chapman, M L
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container_issue 6
container_start_page 1255
container_title MedChemComm
container_volume 8
creator Pryde, D C
Swain, NA
Stupple, P A
West, C W
Marron, B
Markworth, C J
Printzenhoff, D
Lin, Z
Cox, P J
Suzuki, R
McMurray, S
Waldron, G J
Payne, CE
Warmus, J S
Chapman, M L
description In this article, we describe the discovery of an aryl ether series of potent and selective Nav1.3 inhibitors. Based on structural analogy to a similar series of compounds we have previously shown bind to the domain IV voltage sensor region of Nav channels, we propose this series binds in the same location. We describe the development of this series from a published starting point, highlighting key selectivity and potency data, and several studies designed to validate Nav1.3 as a target for pain.
doi_str_mv 10.1039/c7md00131b
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title The discovery of a potent Nav1.3 inhibitor with good oral pharmacokinetics
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