N-(3-(4-[C]甲基哌嗪-1-基)-1-(5-甲基吡啶-2-基)-1H-吡唑-5-基)吡唑并[1,5-a]嘧啶-3-甲酰胺的合成作为一种用于神经炎症中IRAK4酶成像的新型潜在正电子发射断层显像剂。
Synthesis of N-(3-(4-[C]methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide as a new potential PET agent for imaging of IRAK4 enzyme in neuroinflammation.
作者信息
Wang Xiaohong, Xu Wenzhi, Miao Caihong, Dong Fugui, Li Wei, Wang Min, Gao Mingzhang, Zheng Qi-Huang, Xu Zhidong
机构信息
Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, College of Chemistry and Environmental Science, Hebei University, Baoding, Hebei 071002, China.
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
出版信息
Appl Radiat Isot. 2018 Feb;132:6-12. doi: 10.1016/j.apradiso.2017.11.005. Epub 2017 Nov 6.
The reference standard N-(3-(4-methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (9) and its demethylated precursor N-(1-(5-methylpyridin-2-yl)-3-(piperazin-1-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-α]pyrimidine-3-carboxamide (8) were synthesized from pyrazolo[1,5-a]pyrimidine-3-carboxylic acid and ethyl 2-cyanoacetate with overall chemical yield 13% in nine steps and 14% in eight steps, respectively. The target tracer N-(3-(4-[C]methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide ([C]9) was prepared from its precursor with [C]CHOTf through N-[C]methylation and isolated by HPLC combined with SPE in 50-60% radiochemical yield, based on [C]CO and decay corrected to EOB. The radiochemical purity was >99%, and the specific activity at EOB was 370-1110 GBq/μmol.
参考标准品N-(3-(4-甲基哌嗪-1-基)-1-(5-甲基吡啶-2-基)-1H-吡唑-5-基)吡唑并[1,5-a]嘧啶-3-甲酰胺(9)及其去甲基前体N-(1-(5-甲基吡啶-2-基)-3-(哌嗪-1-基)-1H-吡唑-5-基)吡唑并[1,5-α]嘧啶-3-甲酰胺(8)分别由吡唑并[1,5-a]嘧啶-3-羧酸和2-氰基乙酸乙酯合成，总化学产率分别为九步反应13%、八步反应14%。目标示踪剂N-(3-(4-[C]甲基哌嗪-1-基)-1-(5-甲基吡啶-2-基)-1H-吡唑-5-基)吡唑并[1,5-a]嘧啶-3-甲酰胺([C]9)由其前体与[C]CHOTf通过N-[C]甲基化反应制备，并通过HPLC结合SPE分离，基于[C]CO并校正至EOB时的放射性化学产率为50-60%。放射性化学纯度>99%，EOB时的比活度为370-1110 GBq/μmol。
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