Challenges in the development of mGluR5 positive allosteric modulators: the discovery of CPPHA.

Zhao Z, Wisnoski DD, O'Brien JA, Lemaire W, Williams DL, Jacobson MA, Wittman M, Ha SN, Schaffhauser H, Sur C, Pettibone DJ, Duggan ME, Conn PJ, Hartman GD, Lindsley CW
Bioorg Med Chem Lett. 2007 17 (5): 1386-91

PMID: 17210250 · DOI:10.1016/j.bmcl.2006.11.081

This Letter describes, for the first time, the synthesis and SAR, developed through an iterative analog library approach, that led to the discovery of the positive allosteric modulator (PAM) of the metabotropic glutamate receptor mGluR5 CPPHA. Binding to a unique allosteric binding site distinct from other mGluR5 PAMs, CPPHA has been the focus of numerous pharmacology studies by several laboratories.

MeSH Terms (10)

Allosteric Regulation Allosteric Site Animals Benzamides Humans Phthalimides Rats Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate Structure-Activity Relationship

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