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ID: ALA1143275
Journal: Bioorg Med Chem Lett
Title: Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead.
Authors: Williams R, Niswender CM, Luo Q, Le U, Conn PJ, Lindsley CW.
Abstract: This Letter describes the synthesis and SAR of two mGluR4 positive allosteric modulator leads, 6 and 7. VU001171 (6) represents the most potent (EC(50)=650 nM), efficacious (141% Glu Max) and largest fold shift (36-fold) of any mGluR4 PAM reported to date. However, this work highlights the challenges in hit-to-lead for mGluR4 PAMs, with multiple confirmed HTS hits displaying little or no tractable SAR.
CiteXplore: 19097893