WEKO3
アイテム
{"_buckets": {"deposit": "fa2a39eb-614b-41d6-8073-42ffc13a9186"}, "_deposit": {"created_by": 1, "id": "65676", "owners": [1], "pid": {"revision_id": 0, "type": "depid", "value": "65676"}, "status": "published"}, "_oai": {"id": "oai:repo.qst.go.jp:00065676", "sets": ["29"]}, "author_link": ["646949", "646943", "646939", "646951", "646936", "646940", "646937", "646946", "646933", "646938", "646950", "646944", "646932", "646934", "646935", "646947", "646945", "646948", "646942", "646941"], "item_10005_date_7": {"attribute_name": "発表年月日", "attribute_value_mlt": [{"subitem_date_issued_datetime": "2015-05-31", "subitem_date_issued_type": "Issued"}]}, "item_10005_description_5": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Objectives: Metabotropic glutamate receptors (mGlus) are one of the G protein-coupled receptor families, which\nregulate excitatory neurotransmissions on central nerves system. Of these, mGlu4 which together with mGlu6-mGlu8\nreceptors belongs to group III has received a lot of attention because of the potential therapeutic effect by mGlu4\nactivation in several diseases such as Parkinson’s disease. However, to-date no appropriate mGlu4 PET ligand has\nbeen 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\nsynthesis of [11C]ADX88178 via incorporation of 11CH3 group into pyrimidine ring at 6-position.\nMethods: ADX88178 was prepared at 8 steps from ethyl 4-pyrazolecarboxylate. Synthesis of [11C]ADX88178 was\nperformed by C-[11C]methylation reaction of 2 with [11C]CH3I, followed by deprotection of p-methoxybenzyl group in [11C]1 with trifluoroacetic acid.\nResults: 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-\nHPLC. 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\nreaction 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\n43 min of synthesis time from EOB. In the final product solution, the radiochemical purity of [11C]ADX88178 was \u003e98%.\nConclusions: 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\nradiochemical yield is on progress.\nReferences: [1] Emmanuel L. P, et al (2012), J. Pharm. Exp. Ther., 343, 167-177.", "subitem_description_type": "Abstract"}]}, "item_10005_description_6": {"attribute_name": "会議概要(会議名, 開催地, 会期, 主催者等)", "attribute_value_mlt": [{"subitem_description": "21st International Symposium on Radiopharmaceutical Sciences", "subitem_description_type": "Other"}]}, "item_access_right": {"attribute_name": "アクセス権", "attribute_value_mlt": [{"subitem_access_right": "metadata only access", "subitem_access_right_uri": "http://purl.org/coar/access_right/c_14cb"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Fujinaga, Masayuki"}], "nameIdentifiers": [{"nameIdentifier": "646932", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Yamasaki, Tomoteru"}], "nameIdentifiers": [{"nameIdentifier": "646933", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Yui, Joji"}], "nameIdentifiers": [{"nameIdentifier": "646934", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Xie, Lin"}], "nameIdentifiers": [{"nameIdentifier": "646935", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Nengaki, Nobuki"}], "nameIdentifiers": [{"nameIdentifier": "646936", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Hatori, Akiko"}], "nameIdentifiers": [{"nameIdentifier": "646937", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kumata, Katsushi"}], "nameIdentifiers": [{"nameIdentifier": "646938", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Shimoda, Yoko"}], "nameIdentifiers": [{"nameIdentifier": "646939", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kawamura, Kazunori"}], "nameIdentifiers": [{"nameIdentifier": "646940", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Zhang, Ming-Rong"}], "nameIdentifiers": [{"nameIdentifier": "646941", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "藤永 雅之", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "646942", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "山崎 友照", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "646943", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "由井 譲二", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "646944", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "謝 琳", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "646945", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "念垣 信樹", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "646946", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "羽鳥 晶子", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "646947", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "熊田 勝志", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "646948", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "下田 陽子", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "646949", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "河村 和紀", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "646950", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "張 明栄", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "646951", "nameIdentifierScheme": "WEKO"}]}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "conference object", "resourceuri": "http://purl.org/coar/resource_type/c_c94f"}]}, "item_title": "「Synthesis of [11C]ADX88178 via C-[11C]methylation with [11C]CH3I as a PET ligand for imaging of the metabotropic glutamate 4 receptor」", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "「Synthesis of [11C]ADX88178 via C-[11C]methylation with [11C]CH3I as a PET ligand for imaging of the metabotropic glutamate 4 receptor」"}]}, "item_type_id": "10005", "owner": "1", "path": ["29"], "permalink_uri": "https://repo.qst.go.jp/records/65676", "pubdate": {"attribute_name": "公開日", "attribute_value": "2015-06-09"}, "publish_date": "2015-06-09", "publish_status": "0", "recid": "65676", "relation": {}, "relation_version_is_last": true, "title": ["「Synthesis of [11C]ADX88178 via C-[11C]methylation with [11C]CH3I as a PET ligand for imaging of the metabotropic glutamate 4 receptor」"], "weko_shared_id": -1}
「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 |
|||||
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. |
|||||
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 |