{"created":"2023-05-15T14:36:38.897406+00:00","id":47207,"links":{},"metadata":{"_buckets":{"deposit":"29f7981f-4ff7-4fe3-9f0b-25b394e7e611"},"_deposit":{"created_by":1,"id":"47207","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"47207"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00047207","sets":["1"]},"author_link":["471829","471835","471824","471823","471827","471825","471830","471834","471828","471831","471819","471821","471832","471826","471833","471820","471822"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2013-08","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"16","bibliographicPageEnd":"6385","bibliographicPageStart":"6371","bibliographicVolumeNumber":"56","bibliographic_titles":[{"bibliographic_title":"Journal of medicinal chemistry"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Orexin receptors (OXRs) in the brain have been implicated in diverse physiological and neuropsychiatric conditions. Here we describe the design, synthesis, and evaluation of OXR ligands related to (1R,2S)-2-(((2-methyl-4-methoxymethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoropyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide (9a) applicable to positron emission tomography (PET) imaging. Structural features were incorporated to increase binding affinity for OXRs, to enable carbon-11 radiolabeling, and to adjust lipophilicity considered optimal for brain penetration and low nonspecific binding. 9a displayed nanomolar affinity for OXRs, and autoradiography using rat brain sections showed that specific binding of [(11)C]9a was distributed primarily to neocortical layer VI and hypothalamus, consistent with reported localizations of orexin-2 receptors (OX2Rs). In vivo PET study of [(11)C]9a demonstrated moderate uptake of radioactivity into rat and monkey brains under deficiency or blockade of P-glycoprotein, and distribution of PET signals in the brain was in agreement with autoradiographic data. Our approach and findings have provided significant information for development of OX2R PET tracers.","subitem_description_type":"Abstract"}]},"item_8_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Chemical Society"}]},"item_8_relation_13":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"23879299","subitem_relation_type_select":"PMID"}}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1021/jm400772t","subitem_relation_type_select":"DOI"}}]},"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":"Oi, Norihito"}],"nameIdentifiers":[{"nameIdentifier":"471819","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Suzuki, Michiyuki"}],"nameIdentifiers":[{"nameIdentifier":"471820","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Terauchi, Taro"}],"nameIdentifiers":[{"nameIdentifier":"471821","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tokunaga, Masaki"}],"nameIdentifiers":[{"nameIdentifier":"471822","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nakatani, Yosuke"}],"nameIdentifiers":[{"nameIdentifier":"471823","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yamamoto, Noboru"}],"nameIdentifiers":[{"nameIdentifier":"471824","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fukumura, Toshimitsu"}],"nameIdentifiers":[{"nameIdentifier":"471825","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong"}],"nameIdentifiers":[{"nameIdentifier":"471826","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Suhara, Tetsuya"}],"nameIdentifiers":[{"nameIdentifier":"471827","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Higuchi, Makoto"}],"nameIdentifiers":[{"nameIdentifier":"471828","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"大井 紀人","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"471829","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"鈴木 成教","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"471830","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"徳永 正希","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"471831","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"中谷 陽介","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"471832","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"張 明栄","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"471833","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"須原 哲也","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"471834","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"樋口 真人","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"471835","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":"Synthesis and evaluation of novel radioligands for positron emission tomography imaging of the orexin-2 receptor.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Synthesis and evaluation of novel radioligands for positron emission tomography imaging of the orexin-2 receptor."}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2015-08-06"},"publish_date":"2015-08-06","publish_status":"0","recid":"47207","relation_version_is_last":true,"title":["Synthesis and evaluation of novel radioligands for positron emission tomography imaging of the orexin-2 receptor."],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T23:42:38.116672+00:00"}