Abstract:
:Selective metabotropic glutamate receptor 2 (mGluR2) inhibitors have been demonstrated to show therapeutic effects by improving alleviating symptoms of schizophrenic patients in clinical studies. Herein we report the synthesis and preliminary evaluation of a 11C-labeled positron emission tomography (PET) tracer originating from a mGluR2 inhibitor, 3-(cyclopropylmethyl)-7-((4-(4-methoxyphenyl)piperidin-1-yl)methyl)-8-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine (CMTP, 1a). [11C]CMTP ([11C]1a) was synthesized by O-[11C]methylation of desmethyl precursor 1b with [11C]methyl iodide in 19.7 ± 8.9% (n = 10) radiochemical yield (based on [11C]CO2) with >98% radiochemical purity and >74 GBq/μmol molar activity. Autoradiography study showed that [11C]1a possessed moderate in vitro specific binding to mGluR2 in the rat brain, with a heterogeneous distribution of radioactive accumulation in the mGluR2-rich brain tissue sections, such as the cerebral cortex and striatum. PET study indicated that [11C]1a was able to cross the blood-brain barrier and enter the brain, but had very low specific binding in the rat brain. Further optimization for the chemical structure of 1a is necessary to increase binding affinity to mGluR2 and then improve in vivo specific binding in brain.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Kumata K,Zhang Y,Ogawa M,Kurihara Y,Mori W,Hu K,Fujinaga M,Nengaki N,Zhang MRdoi
10.1016/j.bmcl.2020.127555subject
Has Abstractpub_date
2020-12-01 00:00:00pages
127555issue
23eissn
0960-894Xissn
1464-3405pii
S0960-894X(20)30666-1journal_volume
30pub_type
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