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

David C Pryde, N. A. Swain, P. A. Stupple, C. W. West, B. Marron, C. J. Markworth, D. Printzenhoff, Z. Lin, Peter John Cox, Ryoichi Suzuki, S. McMurray, G. J. Waldron, C. E. Payne, J. S. Warmus, M. L. Chapman

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1255-1267
Number of pages13
JournalMedChemComm
Volume8
Issue number6
DOIs
Publication statusPublished - 2017
Externally publishedYes

Cite this

Pryde, D. C., Swain, N. A., Stupple, P. A., West, C. W., Marron, B., Markworth, C. J., ... Chapman, M. L. (2017). The discovery of a potent Nav1.3 inhibitor with good oral pharmacokinetics. MedChemComm, 8(6), 1255-1267. https://doi.org/10.1039/c7md00131b
Pryde, David C ; Swain, N. A. ; Stupple, P. A. ; West, C. W. ; Marron, B. ; Markworth, C. J. ; Printzenhoff, D. ; Lin, Z. ; Cox, Peter John ; Suzuki, Ryoichi ; McMurray, S. ; Waldron, G. J. ; Payne, C. E. ; Warmus, J. S. ; Chapman, M. L. / The discovery of a potent Nav1.3 inhibitor with good oral pharmacokinetics. In: MedChemComm. 2017 ; Vol. 8, No. 6. pp. 1255-1267.
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abstract = "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.",
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Pryde, DC, Swain, NA, Stupple, PA, West, CW, Marron, B, Markworth, CJ, Printzenhoff, D, Lin, Z, Cox, PJ, Suzuki, R, McMurray, S, Waldron, GJ, Payne, CE, Warmus, JS & Chapman, ML 2017, 'The discovery of a potent Nav1.3 inhibitor with good oral pharmacokinetics', MedChemComm, vol. 8, no. 6, pp. 1255-1267. https://doi.org/10.1039/c7md00131b

The discovery of a potent Nav1.3 inhibitor with good oral pharmacokinetics. / Pryde, David C; Swain, N. A.; Stupple, P. A.; West, C. W.; Marron, B.; Markworth, C. J.; Printzenhoff, D.; Lin, Z.; Cox, Peter John; Suzuki, Ryoichi; McMurray, S.; Waldron, G. J.; Payne, C. E.; Warmus, J. S.; Chapman, M. L.

In: MedChemComm, Vol. 8, No. 6, 2017, p. 1255-1267.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Pryde, David C

AU - Swain, N. A.

AU - Stupple, P. A.

AU - West, C. W.

AU - Marron, B.

AU - Markworth, C. J.

AU - Printzenhoff, D.

AU - Lin, Z.

AU - Cox, Peter John

AU - Suzuki, Ryoichi

AU - McMurray, S.

AU - Waldron, G. J.

AU - Payne, C. E.

AU - Warmus, J. S.

AU - Chapman, M. L.

PY - 2017

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