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  • Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain.

Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain.

Bioorganic & medicinal chemistry letters (2011-05-17)
Sultan Chowdhury, Mikhail Chafeev, Shifeng Liu, Jianyu Sun, Vandna Raina, Ray Chui, Wendy Young, Rainbow Kwan, Jianmin Fu, Jay A Cadieux
ABSTRACT

Starting from the oxindole 2a identified through a high-throughput screening campaign, a series of Na(V)1.7 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 Na(V)1.7 blocker. This lead compound, which in turn showed a further 10-fold increase in potency, represents a promising structure for further optimization efforts.

MATERIALS
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Product Description

Sigma-Aldrich
Triethylsilane, 99%