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Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Jun2011, Vol. 21 Issue 12, p3676-3681. 6p. - Publication Year :
- 2011
-
Abstract
- Abstract: Starting from the oxindole 2a identified through a high-throughput screening campaign, a series of NaV1.7 blockers were developed. Following the elimination of undesirable structural features, preliminary optimization of the oxindole C-3 and N-1 substituents afforded the simplified analogue 9b, which demonstrated a 10-fold increase in target potency versus the original HTS hit. A scaffold rigidification strategy then led to the discovery of XEN907, a novel spirooxindole NaV1.7 blocker. This lead compound, which in turn showed a further 10-fold increase in potency, represents a promising structure for further optimization efforts. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 21
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 61173374
- Full Text :
- https://doi.org/10.1016/j.bmcl.2011.04.088