{"created":"2023-05-15T14:55:42.455187+00:00","id":75641,"links":{},"metadata":{"_buckets":{"deposit":"563fa7d4-bb6c-4b02-ba6a-20cd17d96c42"},"_deposit":{"created_by":1,"id":"75641","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"75641"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00075641","sets":["1"]},"author_link":["761490","761510","761485","761491","761505","761479","761494","761519","761499","761488","761512","761493","761495","761492","761487","761503","761513","761515","761496","761483","761518","761521","761507","761480","761517","761478","761504","761481","761497","761482","761477","761516","761514","761498","761520","761501","761508","761511","761506","761486","761509","761500","761502","761489","761484"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-03","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"7","bibliographicPageEnd":"3353","bibliographicPageStart":"3336","bibliographicVolumeNumber":"62","bibliographic_titles":[{"bibliographic_title":"Journal of Medicinal Chemistry"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":" Monoacylglycerol lipase (MAGL) is a serine hydrolase that degrades 2-arachidonoylglycerol (2-AG) in the endocannabinoid system (eCB). Selective inhibition of MAGL has emerged as a potential therapeutic approach for the treatment of diverse pathological conditions, including chronic pain, inflammation, cancer, and neurodegeneration. Herein, we disclose a novel array of reversible and irreversible MAGL inhibitors by means of “tail switching” on a piperazinyl azetidine scaffold. We developed a lead irreversible-binding MAGL inhibitor 8 and reversible-binding compounds 17 and 37, which are amenable for radiolabeling with 11C or18F. [11C]8 ([11C]MAGL-2-11) exhibited high brain uptake and excellent binding specificity in the brain toward MAGL. Reversible radioligands [11C]17 ([11C]PAD) and [18F]37 ([18F]MAGL-4-11) also demonstrated excellent in vivo binding specificity toward MAGL in peripheral organs. This work may pave the way for the development of MAGL-targeted positron emission tomography tracers with tunability in reversible and irreversible binding mechanisms. ","subitem_description_type":"Abstract"}]},"item_8_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"ACS Publications"}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1021/acs.jmedchem.8b01778","subitem_relation_type_select":"DOI"}}]},"item_8_relation_17":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b01719","subitem_relation_type_select":"URI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0022-2623","subitem_source_identifier_type":"ISSN"}]},"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":"Chen, Zhen"}],"nameIdentifiers":[{"nameIdentifier":"761477","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Mori, Wakana"}],"nameIdentifiers":[{"nameIdentifier":"761478","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Deng, Xiaoyun"}],"nameIdentifiers":[{"nameIdentifier":"761479","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Cheng, Ran"}],"nameIdentifiers":[{"nameIdentifier":"761480","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ogasawara, Daisuke"}],"nameIdentifiers":[{"nameIdentifier":"761481","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Genwei"}],"nameIdentifiers":[{"nameIdentifier":"761482","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"A. Schafroth, Michael"}],"nameIdentifiers":[{"nameIdentifier":"761483","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Dahl, Kenneth"}],"nameIdentifiers":[{"nameIdentifier":"761484","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fu, Hualong"}],"nameIdentifiers":[{"nameIdentifier":"761485","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hatori, Akiko"}],"nameIdentifiers":[{"nameIdentifier":"761486","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Shao, Tuo"}],"nameIdentifiers":[{"nameIdentifier":"761487","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yiding"}],"nameIdentifiers":[{"nameIdentifier":"761488","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yamasaki, Tomoteru"}],"nameIdentifiers":[{"nameIdentifier":"761489","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Xiaofei"}],"nameIdentifiers":[{"nameIdentifier":"761490","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Rong, Jian"}],"nameIdentifiers":[{"nameIdentifier":"761491","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yu, Qingzhen"}],"nameIdentifiers":[{"nameIdentifier":"761492","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kuan, Hu"}],"nameIdentifiers":[{"nameIdentifier":"761493","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujinaga, Masayuki"}],"nameIdentifiers":[{"nameIdentifier":"761494","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Xie, Lin"}],"nameIdentifiers":[{"nameIdentifier":"761495","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kumata, Katsushi"}],"nameIdentifiers":[{"nameIdentifier":"761496","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Gou, Yuancheng"}],"nameIdentifiers":[{"nameIdentifier":"761497","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Chen, Jingjin"}],"nameIdentifiers":[{"nameIdentifier":"761498","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Gu, Shuyin"}],"nameIdentifiers":[{"nameIdentifier":"761499","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Bao, Liang"}],"nameIdentifiers":[{"nameIdentifier":"761500","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Lu, Wang"}],"nameIdentifiers":[{"nameIdentifier":"761501","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Lee Collier, Thomas"}],"nameIdentifiers":[{"nameIdentifier":"761502","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Vasdev, Neil"}],"nameIdentifiers":[{"nameIdentifier":"761503","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Shao, Yihan"}],"nameIdentifiers":[{"nameIdentifier":"761504","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Jun-An, Ma"}],"nameIdentifiers":[{"nameIdentifier":"761505","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"F. 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