Discovery of XEN907, a spirooxindole blocker of Na V 1.7 for the treatment of pain

S Chowdhury, M Chafeev, S Liu, J Sun, V Raina…

Index: Chowdhury, Sultan; Chafeev, Mikhail; Liu, Shifeng; Sun, Jianyu; Raina, Vandna; Chui, Ray; Young, Wendy; Kwan, Rainbow; Fu, Jianmin; Cadieux, Jay A. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 12 p. 3676 - 3681

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Citation Number: 41

Abstract

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 ...