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「Synthesis of [11C]ADX88178 via C-[11C]methylation with [11C]CH3I as a PET ligand for imaging of the metabotropic glutamate 4 receptor」
https://repo.qst.go.jp/records/65676
https://repo.qst.go.jp/records/65676763a9f6d-cbe0-4ab1-a7aa-9d1ea311eb73
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-06-09 | |||||
| タイトル | ||||||
| タイトル | 「Synthesis of [11C]ADX88178 via C-[11C]methylation with [11C]CH3I as a PET ligand for imaging of the metabotropic glutamate 4 receptor」 | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Fujinaga, Masayuki
× Fujinaga, Masayuki× Yamasaki, Tomoteru× Yui, Joji× Xie, Lin× Nengaki, Nobuki× Hatori, Akiko× Kumata, Katsushi× Shimoda, Yoko× Kawamura, Kazunori× Zhang, Ming-Rong× 藤永 雅之× 山崎 友照× 由井 譲二× 謝 琳× 念垣 信樹× 羽鳥 晶子× 熊田 勝志× 下田 陽子× 河村 和紀× 張 明栄 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: Metabotropic glutamate receptors (mGlus) are one of the G protein-coupled receptor families, which regulate excitatory neurotransmissions on central nerves system. Of these, mGlu4 which together with mGlu6-mGlu8 receptors belongs to group III has received a lot of attention because of the potential therapeutic effect by mGlu4 activation in several diseases such as Parkinson’s disease. However, to-date no appropriate mGlu4 PET ligand has been employed. Recently, Le Poul et al. has developed ADX88178 as a potent and selective ligand for mGlu4 [1]. C-[11C]methylation of pyrimidine ring at 2- or 6-position has not been previously reported. In this study, we report the synthesis of [11C]ADX88178 via incorporation of 11CH3 group into pyrimidine ring at 6-position. Methods: ADX88178 was prepared at 8 steps from ethyl 4-pyrazolecarboxylate. Synthesis of [11C]ADX88178 was performed by C-[11C]methylation reaction of 2 with [11C]CH3I, followed by deprotection of p-methoxybenzyl group in [11C]1 with trifluoroacetic acid. Results: C-[11C]methylation of 2 with [11C]CH3I in the presence of Pd2(dba)3, P(o-tol)3, CuCl, and K2CO3 at 80oC for 5 min only produced [11C]1 in 40% yield, which was determined by analyzing the reaction mixture using radio- HPLC. Instead of K2CO3, using CsF as a base, the C-[11C]methylation yield was improved up to 90%. After the [11C]methylation and removal of DMF, debenzylation of [11C]1 with TFA at 100oC for 5 min and purification for the reaction mixture using semi-preparative HPLC gave [11C]ADX88178 in 3 % radiochemical yield (based on the total [11C]CO2, corrected for decay). Starting from 22 GBq of [11C]CO2, 0.13 GBq of [11C]ADX88178 was produced within 43 min of synthesis time from EOB. In the final product solution, the radiochemical purity of [11C]ADX88178 was >98%. Conclusions: We succeeded in the synthesis of [11C]ADX88178 by 2 step reactions of C-11C coupling and debenzylation. This novel PET ligand is now available for evaluation in mice or rat and improvement for the radiochemical yield is on progress. References: [1] Emmanuel L. P, et al (2012), J. Pharm. Exp. Ther., 343, 167-177. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 21st International Symposium on Radiopharmaceutical Sciences | |||||
| 発表年月日 | ||||||
| 日付 | 2015-05-31 | |||||
| 日付タイプ | Issued | |||||
