Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1370817 | Bioorganic & Medicinal Chemistry Letters | 2011 | 6 Pages |
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.
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Related Topics
Physical Sciences and Engineering
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Organic Chemistry
Authors
Sultan Chowdhury, Mikhail Chafeev, Shifeng Liu, Jianyu Sun, Vandna Raina, Ray Chui, Wendy Young, Rainbow Kwan, Jianmin Fu, Jay A. Cadieux,