{"created":"2023-05-15T14:37:28.181699+00:00","id":48327,"links":{},"metadata":{"_buckets":{"deposit":"5a5f1e8e-9135-4382-9d27-6f166b7f4be1"},"_deposit":{"created_by":1,"id":"48327","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"48327"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00048327","sets":["1"]},"author_link":["485709","485714","485720","485716","485719","485722","485718","485724","485710","485711","485723","485713","485721","485715","485717","485712"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2017-07","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"17","bibliographicPageEnd":"4117","bibliographicPageStart":"4114","bibliographicVolumeNumber":"27","bibliographic_titles":[{"bibliographic_title":"Bioorganic & Medicinal Chemistry Letters"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Cannabinoid receptor type 1 (CB1) is mainly expressed in the brain, as well as being expressed in functional relevant concentrations in various peripheral tissues. 1-(4-Chlorophenyl)-3-(3-(6-(pyrrolidin-1-yl)pyridin-2-yl)phenyl)urea (PSNCBAM-1, 1) was developed as a potent allosteric antagonist for CB1 and its oral administration led to reductions in the appetite and body weight of rats. Several analogs of 1 (compounds 2 and 3) were recently identified through a series of structure-activity relationship studies. Herein, we report the synthesis of radiolabeled analogs of these compounds using [11C]COCl2, and an evaluation of their potential as PET ligands for CB1 imaging using in vitro and in vivo techniques. [11C]2 and [11C]3 were successfully synthesized in two steps using [11C]COCl2. The radiochemical yields of [11C]2 and [11C]3 were 17 ± 8% and 20 ± 9% (decay-corrected to the end of bombardment, based on [11C]CO2). The specific activities of [11C]2 and [11C]3 were 42 ± 36 and 37 ± 13 GBq/μmol, respectively. The results of an in vitro binding assay using brown adipose tissue (BAT) homogenate showed that the binding affinity of 2 for CB1 (KD = 15.3 µM) was much higher than that of 3 (KD = 26.0 µM). PET studies with [11C]2 showed a high uptake of radioactivity in BAT, which decreased considerably in animals pretreated with AM281 (a selective allosteric antagonist for CB1). In conclusion, [11C]2 may be a useful PET ligand for imaging peripheral CB1 in BAT.\n2009 Elsevier Ltd. All rights reserved.","subitem_description_type":"Abstract"}]},"item_8_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier"}]},"item_8_relation_13":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"28757061","subitem_relation_type_select":"PMID"}}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1016/j.bmcl.2017.07.040","subitem_relation_type_select":"DOI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0960-894X ","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":"Yamasaki, Tomoteru"}],"nameIdentifiers":[{"nameIdentifier":"485709","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujinaga, Masayuki"}],"nameIdentifiers":[{"nameIdentifier":"485710","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Shimoda, Yoko"}],"nameIdentifiers":[{"nameIdentifier":"485711","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Mori, Wakana"}],"nameIdentifiers":[{"nameIdentifier":"485712","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yiding"}],"nameIdentifiers":[{"nameIdentifier":"485713","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Wakizaka, Hidekatsu"}],"nameIdentifiers":[{"nameIdentifier":"485714","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ogawa, Masanao"}],"nameIdentifiers":[{"nameIdentifier":"485715","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong"}],"nameIdentifiers":[{"nameIdentifier":"485716","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"山崎 友照","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"485717","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"藤永 雅之","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"485718","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"下田 陽子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"485719","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"森 若菜","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"485720","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"張 一鼎","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"485721","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"脇坂 秀克","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"485722","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"小川 政直","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"485723","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"張 明栄","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"485724","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":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Radiosynthesis and evaluation of new PET ligands for peripheral cannabinoid receptor type 1 imaging","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Radiosynthesis and evaluation of new PET ligands for peripheral cannabinoid receptor type 1 imaging"}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-09-21"},"publish_date":"2017-09-21","publish_status":"0","recid":"48327","relation_version_is_last":true,"title":["Radiosynthesis and evaluation of new PET ligands for peripheral cannabinoid receptor type 1 imaging"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T23:29:22.959701+00:00"}