912667-95-9Relevant articles and documents
Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain
Chowdhury, Sultan,Chafeev, Mikhail,Liu, Shifeng,Sun, Jianyu,Raina, Vandna,Chui, Ray,Young, Wendy,Kwan, Rainbow,Fu, Jianmin,Cadieux, Jay A.
, p. 3676 - 3681 (2011/08/06)
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.