title: Synthesis of [(11)C]GSK1482160 as a new PET agent for targeting P2X(7) receptor.
abstract: The authentic standards GSK1482160 and its isomer, as well as the radiolabeling precursors desmethyl-GSK1482160 and Boc-protected desmethyl-GSK1482160 were synthesized from L-pyroglutamic acid, methyl L-pyroglutamate and 2-chloro-3-(trifluoromethyl)benzylamine with overall chemical yield 27-28% in 3 steps, 58% in 4 steps, 76% in 1 step and 33% in 2 steps, respectively. [(11)C]GSK1482160 was prepared from either desmethyl-GSK1482160 or Boc-protected desmethyl-GSK1482160 with [(11)C]CH3OTf through N-[(11)C]methylation and isolated by HPLC combined with SPE in 40-50% and 30-40% radiochemical yield, respectively, based on [(11)C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity at EOB was 370-1110 GBq/μmol with a total synthesis time of ∼40-min from EOB.
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors.forename: Mingzhang
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Green
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hutchins
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA. Electronic address: qzheng@iupui.edu.
authors.forename: Qi-Huang
authors.initials: QH
authors.lastname: Zheng
mesh_terms: D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D057054:Molecular Imaging; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D011761:Pyrrolidonecarboxylic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D052616:Solid Phase Extraction; D013329:Structure-Activity Relationship
chemical_list: D002250:Carbon Radioisotopes; C000604998:N-(2-chloro-3-(trifluoromethyl)benzyl)-N-methyl-5-oxopyrrolidine-2-carboxamide; C546468:P2RX7 protein, human; D019275:Radiopharmaceuticals; D058486:Receptors, Purinergic P2X7; D011761:Pyrrolidonecarboxylic Acid
keywords: Neuroinflammation; P2X(7) receptor; Positron emission tomography (PET); Radiosynthesis; [(11)C]GSK1482160