Design, Synthesis, and Structure− Activity Relationships of Novel Bicyclic Azole-amines as Negative Allosteric Modulators of Metabotropic Glutamate Receptor 5

…, J Wang, Z Guo, Z Huang, C Wu, L Hardy…

Index: Burdi, Douglas F.; Hunt, Rachel; Fan, Lei; Hu, Tao; Wang, Jun; Guo, Zihong; Huang, Zhiqiang; Wu, Chengde; Hardy, Larry; Detheux, Michel; Orsini, Michael A.; Quinton, Maria S.; Lew, Robert; Spear, Kerry Journal of Medicinal Chemistry, 2010 , vol. 53, # 19 p. 7107 - 7118

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Citation Number: 13

Abstract

A novel series of diaryl bicyclic azole-amines that are potent selective negative modulators of metabotropic glutamate receptor 5 (mGluR5) were identified through rational design. An initial hit compound 5a of modest potency (IC50= 1.2 μM) was synthesized. Evaluation of structure− activity relationships (SAR) on the left-hand side of the molecule revealed a preference for a 2-substituted pyridine group linked directly to the central heterocycle. ...