Selective iGluR5 antagonists for the treatment of migraine

MEDI 218

Paul L. Ornstein, ornsteinpl@lilly.com, Sandra A. Filla, Kevin J. Hudziak, Smriti Iyengar, David Bleakman, Ken H. Ho, Donna K. Dieckman, Amy C. Smith, and Kirk W. Johnson. Discovery Research, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285
The discovery of sumatriptan and related compounds has revolutionized the treatment of migraine. However, there still remains a need to identify novel therapies with distinct mechanisms of action to enhance the arsenal available to physicians to treat this condition. Our identification of novel, selective antagonists for iGluR5 kainate receptors allowed us to generate pharmacological evidence in support of these agents as novel migraine therapy. Through structure activity studies on a series of 6-substituted decahydroisoquinolines, we've discovered novel, potent, subtype selective iGluR5 antagonists. In this talk we will present aspects of these SAR studies as well as data that show the potential for these compounds to treat migraine.