{"created":"2023-05-15T14:47:55.137961+00:00","id":65676,"links":{},"metadata":{"_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":["10:29"]},"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 >98%.\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"],"pubdate":{"attribute_name":"公開日","attribute_value":"2015-06-09"},"publish_date":"2015-06-09","publish_status":"0","recid":"65676","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_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T20:57:29.637421+00:00"}