N-(6,7-Dichloro-2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)-N-alkylsulfonamides as peripherally restricted N-methyl-d-aspartate receptor antagonists for the treatment of pain

It has been hypothesized that peripherally restricted NMDA receptor antagonists may be effective analgesics for osteoarthritis pain. A class of novel quinoxalinedione atropisomers, first discovered for an NMDA receptor antagonist program for the treatment of stroke, was evaluated and further optimized with the goal of finding peripherally restricted NMDA receptor antagonists.

A series of quinoxalinedione sulfonamides with potent NMDA receptor antagonist activity are discussed as potential pain therapeutics. The antagonists were optimized for oral bioavailability and decreased capacity to cross the blood–brain barrier.Figure optionsDownload as PowerPoint slide