title: Synthesis of [11C]HG-10-102-01 as a new potential PET agent for imaging of LRRK2 enzyme in Parkinson's disease.
abstract: The reference standard (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (HG-10-102-01) and its precursor (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-hydroxyphenyl)(morpholino)methanone (desmethyl-HG-10-102-01) were synthesized from 2,4,5-trichloropyrimide and 3-methoxy-4-nitrobenzoic acid with overall chemical yield 49% in four steps and 14% in five steps, respectively. The target tracer (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-[11C]methoxyphenyl)(morpholino)methanone ([11C]HG-10-102-01) was prepared from the precursor desmethyl-HG-10-102-01 with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 45-55% radiochemical yield, based on [11C]CO2and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370-1110GBq/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: 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: Mingzhang
authors.initials: M
authors.lastname: Gao
authors.affiliation: Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, College of Chemistry and Environmental Science, Hebei University, Baoding, Hebei 071002, China.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Xu
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: D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000378:metabolism*; D010300:Parkinson Disease / Q000201:enzymology*; D049268:Positron-Emission Tomography; D011743:Pyrimidines / Q000138:chemical synthesis*; D019275:Radiopharmaceuticals; D062366:para-Aminobenzoates / Q000138:chemical synthesis*
chemical_list: C000622719:HG-10-102-01; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D062366:para-Aminobenzoates; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: Leucine-rich repeat kinase 2 (LRRK2); Parkinson’s disease (PD); Positron emission tomography (PET); Radiosynthesis; [(11)C]HG-10-102-01