The metabotropic glutamate receptor subtype 5 has evolved into a promising target for the treatment of various diseases of the central nervous system, such as Fragile X and L-DOPA induced dyskinesia. One of the most advanced clinical compound is Novartis' AFQ-056 (Mavoglurant), which served us as a template for a scaffold hopping approach, generating a structurally diverse set of potent analogs. Both the limited aqueous solubility and the relatively poor metabolic stability of AFQ-056 were improved with hexahydrocyclopenta[c]pyrrole derivative 54a, which proved to be a valuable candidate for further development.
Keywords: AFQ-056; Allosteric modulator; CIZDIEPYKQXGQG-UHFFFAOYSA-N; Metabotropic glutamate receptor; OFNVYYXEOJUGRH-UHFFFAOYSA-N; SONLNLJEFBMKGV-UHFFFAOYSA-N; Scaffold hopping; mGluR5.
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