Baumann CA Mu L Johannsen S Honer M Schubiger PA Ametamey SM 2010 The metabotropic glutamate receptor subtype 5 (mGluR5) is recognized to be involved in numerous brain disorders. In an effort to obtain a fluorine-18 labeled analogue of the mGluR5 PET tracer [(11)C]ABP688, 13 novel ligands based on the core structure of ABP688 were synthesized. Molecules in which the methyl group at the oxime functionality of ABP688 was replaced by fluorobenzonitriles, fluoropyridines, and fluorinated oxygen containing alkyl side chains were investigated. Substituents at the oxime functionality are well tolerated and resulted in five candidates with K(i) values below 10 nM. The most promising candidate, (E)-3-(pyridin-2-ylethynyl)cyclohex-2-enone-O-2-(2-fluoroethoxy)ethyloxime (38, K(i) = 3.8 nM), was radiolabeled with fluorine-18. Scatchard analysis of [(18)F]38 which modeled best for two sites pointed to high binding affinity (K(D1) = 0.61 +/- 0.19 nM and K(D2) = 13.73 +/- 4.69 nM) too. These data strongly suggest the further evaluation of [(18)F]38 as a candidate for imaging the mGluR5. https://sonar.ch/global/documents/143170 eng info:eu-repo/semantics/altIdentifier/doi/10.1021/jm901850k info:eu-repo/semantics/altIdentifier/pmid/20411954 Journal of medicinal chemistry. - 2010 Alkynes Animals Binding, Competitive Brain Fluorine Radioisotopes In Vitro Techniques Male Models, Molecular Oximes Positron-Emission Tomography Protein Binding Pyridines Rats Rats, Sprague-Dawley Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate Stereoisomerism Structure-Activity Relationship Structure-activity relationships of fluorinated (E)-3-((6-methylpyridin-2-yl)ethynyl)cyclohex-2-enone-O-methyloxime (ABP688) derivatives and the discovery of a high affinity analogue as a potential candidate for imaging metabotropic glutamate recepors subtype 5 (mGluR5) with positron emission tomography (PET). http://purl.org/coar/resource_type/c_6501