PubMed 21570288

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Nav1.7

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

Authors: Sultan Chowdhury, Mikhail Chafeev, Shifeng Liu, Jianyu Sun, Vandna Raina, Ray Chui, Wendy Young, Rainbow Kwan, Jianmin Fu, Jay A Cadieux

Journal, date & volume: Bioorg. Med. Chem. Lett., 2011 Jun 15 , 21, 3676-81

PubMed link:

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.