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

doi:10.1016/j.bmcl.2017.02.019

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. Epub 2017 Feb 11.

Authors

Min Wang¹, Mingzhang Gao¹, Zhidong Xu², Qi-Huang Zheng³

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: qzheng@iupui.edu.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Humans
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / metabolism*
Parkinson Disease / enzymology*
Positron-Emission Tomography*
Pyrimidines / chemical synthesis*
Radiopharmaceuticals
para-Aminobenzoates / chemical synthesis*

Substances

HG-10-102-01
Pyrimidines
Radiopharmaceuticals
para-Aminobenzoates
LRRK2 protein, human
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2