Synthesis of [11C]HG-10-102-01 as a new potential PET agent for imaging of LRRK2 enzyme in Parkinson's disease

  • Bioorg Med Chem Lett. 2017 Mar 15;27(6):1351-1355. doi: 10.1016/j.bmcl.2017.02.019.
Min Wang  1 ,  Mingzhang Gao  1 ,  Zhidong Xu  2 ,  Qi-Huang Zheng  3
Affiliations
  • 1. Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
  • 2. Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, College of Chemistry and Environmental Science, Hebei University, Baoding, Hebei 071002, China.
  • 3. Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA. Electronic address: [email protected].
PMID: 28223019 DOI: 10.1016/j.bmcl.2017.02.019
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]CO2 and 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.

Keywords
Leucine-rich repeat kinase 2 (LRRK2); Parkinson’s disease (PD); Positron emission tomography (PET); Radiosynthesis; [(11)C]HG-10-102-01.
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