Discovery and Preclinical Characterization of 1‑Methyl‑3-(4‑methylpyridin‑3‑yl)‑6‑(pyridin‑2‑ylmethoxy)‑1H‑pyrazolo-[3,4‑b]pyrazine (PF470): A Highly Potent, Selective, and Efficacious Metabotropic Glutamate Receptor 5 (mGluR5) Negative Allosteric Modulator - Zhang, Lei; Balan, Gayatri; Barreiro, Gabriela; Boscoe, Brian P; Chenard, Lois K; Cianfrogna, Julie; Claffey, Michelle M; Chen, Laigao; Coffman, Karen J; Drozda, Susan E; Dunetz, Joshua R; Fonseca, Kari R; et al. (Journal of medicinal chemistry, 2014)
Keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Administration, Oral; Allosteric Regulation; Animals; Antiparkinson Agents - adverse effects; Biological Availability; Cell Membrane Permeability; Chemistry, Medicinal; Dogs; Dyskinesia, Drug-Induced - drug therapy; HEK293 Cells; Humans; Hypersensitivity, Delayed - chemically induced; Levodopa - adverse effects; Life Sciences & Biomedicine; Macaca fascicularis; Madin Darby Canine Kidney Cells; Male; Microsomes, Liver - metabolism; Models, Molecular; Parkinson Disease - drug therapy; Parkinson Disease - etiology; Parkinson Disease - physiopathology; Pharmacology & Pharmacy; Pyrazines - chemical synthesis; Pyrazines - pharmacology; Pyrazines - toxicity; Pyrazoles - chemical synthesis; Pyrazoles - pharmacology; Pyrazoles - toxicity; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptor, Metabotropic Glutamate 5 - metabolism; Science & Technology; Structure-Activity Relationship; CENTRAL-NERVOUS-SYSTEM; DOPA-INDUCED DYSKINESIA; ANTAGONIST; ALIGNMENT; MONKEYS; EFFICIENCY