Radiosynthesis of a carbon-11-labeled AMPAR allosteric modulator as a new PET radioligand candidate for imaging of Alzheimer's disease

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:29

Article

Miao, Caihong¹  Dong, Fugui¹  Jia, Limeng¹  Li, Wei¹  Wang, Min²  Zheng, Qi-Huang²  Xu, Zhidong^1,3,4 

[1] Hebei Univ, Coll Chem & Environm Sci, Minist Educ, Key Lab Med Chem & Mol Diag, Baoding 071002, Hebei, Peoples R China

[2] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, 1345 West 16th St Room 202, Indianapolis, IN 46202 USA

[3] Hebei Univ Sci & Technol, Coll Chem & Pharmaceut Engn, Key Lab Mol Chem Med Hebei Prov, Shijiazhuang 050018, Hebei, Peoples R China

[4] Shijiazhuang Vince Pharmatech Co Ltd, Shijiazhuang 050030, Hebei, Peoples R China

关键词: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR);    Carbon-11-labeled AMPAR allosteric modulator;    Radiosynthesis;    Positron emission tomography (PET);    Alzheimer's disease (AD);   

DOI  :  10.1016/j.bmcl.2019.03.027

来源: Elsevier

【 摘 要 】

To develop PET tracers for imaging of Alzheimer's disease, a new carbon-11-labeled AMPAR allosteric modulator 4-cyclopropyl-7-(3-[C-11] methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide ([C-11] 8) has been synthesized. The reference standard 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide (8) and its corresponding desmethylated precursor 4-cyclopropyl-7-(3-hydroxyphenoxy)3,4- dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide (9) were synthesized from 4-methoxyabiline and chlorosulfonyl isocyanate in eight and nine steps with 3% and 1% overall chemical yield, respectively. The target tracer [C-11] 8 was prepared from the precursor 9 with [C-11] CH3OTf through O-[C-11] methylation and isolated by HPLC combined with SPE in 10-15% radiochemical yield, based on [C-11] CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was> 99%, and the molar activity (AM) at EOB was 370-740 GBq/mu mol with a total synthesis time of 35-40-minutes from EOB.

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