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

Min Wang, Mingzhang Gao, Zhidong Xu, Qi-Huang Zheng

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 370–1110 GBq/μmol with a total synthesis time of ∼40-min from EOB.

Original languageEnglish (US)
Pages (from-to)1351-1355
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number6
DOIs
StatePublished - Mar 15 2017

Fingerprint

Morpholinos
Parkinson Disease
4-nitrobenzoic acid
Imaging techniques
Enzymes
Methylation
High Pressure Liquid Chromatography

Keywords

  • Leucine-rich repeat kinase 2 (LRRK2)
  • Parkinson's disease (PD)
  • Positron emission tomography (PET)
  • Radiosynthesis
  • [C]HG-10-102-01

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Synthesis of [11C]HG-10-102-01 as a new potential PET agent for imaging of LRRK2 enzyme in Parkinson's disease. / Wang, Min; Gao, Mingzhang; Xu, Zhidong; Zheng, Qi-Huang.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 27, No. 6, 15.03.2017, p. 1351-1355.

Research output: Contribution to journalArticle

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