{"created":"2023-05-15T14:34:08.239415+00:00","id":44203,"links":{},"metadata":{"_buckets":{"deposit":"d32b6b67-c594-4877-ae14-9f90949404d2"},"_deposit":{"created_by":1,"id":"44203","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"44203"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00044203","sets":["1"]},"author_link":["439184","439183","439185","439194","439189","439186","439188","439181","439180","439187","439191","439193","439195","439192","439182","439190"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2005-12","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"1818","bibliographicPageStart":"1811","bibliographicVolumeNumber":"13","bibliographic_titles":[{"bibliographic_title":"Bioorganic & Medicinal Chemistry"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoromethoxy-d2-5-methoxybenzyl)acetamide ([18F]2)is a potent ligand (IC50,1.71 nM) for peripheral benzodiazepine receptor (PBR).However,in vivo evaluation on rodents and primates showed that this ligand was unstable and rapidly metabolized to [18F]F- by defluorination of the [18F]fluoromethyl moiety. In this study, we designed a deuterium-substituted analogue, N-(5-fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoromethoxy-d2-5-methoxybenzyl)acetamide ([18F]5) as a radioligand for PBR to reduce the in vivo metabolic rate of the non-deuterated [18F]2. The design principle was based on the hypothesis that the deuterium substitution may reduce the rate of defluorination initiated by cleavage of the C-H bond without altering the binding affinity for PBR. The non-radioactive 5 was prepared by reacting diiodomethane-d2 (CD2I2, 6) with a phenol precursor 7, followed by treatment with tetrabutylammonium fluoride. The ligand [18F]5 was synthesized by the alkylation of 7 with [18F]fluoromethyl iodide-d2 ([18F]FCD2I, [18F]9).  Compound 5 displayed a similar in vitro affinity to PBR (IC50,1.90 nM) with 2.  In vivo evaluation demonstrated that [18F]5 was metabolized by defluorination to [18F]F-as a main radioactive component, but its metabolic rate was slower than that of [18F]2 in the brain of mice. The deuterium substitution decreased the radioactivity level of [18F]5 in the bone of mouse, augmented by the percentage of specific binding to PBR in the rat brain determined by ex vivo autoradiography. However,the PET image of[18F]5 for monkey brain showed high radioactivity in the brain and skull, suggesting a possible species difference between rodents and primates.","subitem_description_type":"Abstract"}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0968-0896","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":"Zhang, Ming-Rong"}],"nameIdentifiers":[{"nameIdentifier":"439180","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Maeda, Jun"}],"nameIdentifiers":[{"nameIdentifier":"439181","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ito, Takehito"}],"nameIdentifiers":[{"nameIdentifier":"439182","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Okauchi, Takashi"}],"nameIdentifiers":[{"nameIdentifier":"439183","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ogawa, Masanao"}],"nameIdentifiers":[{"nameIdentifier":"439184","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Noguchi, Junko"}],"nameIdentifiers":[{"nameIdentifier":"439185","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Suhara, Tetsuya"}],"nameIdentifiers":[{"nameIdentifier":"439186","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Halldin, Christer"}],"nameIdentifiers":[{"nameIdentifier":"439187","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Suzuki, Kazutoshi"}],"nameIdentifiers":[{"nameIdentifier":"439188","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"張 明栄","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"439189","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"前田 純","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"439190","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"岡内 隆","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"439191","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"小川 政直","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"439192","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"須原 哲也","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"439193","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"ハルディン クリスタ","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"439194","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"鈴木 和年","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"439195","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 N-(5-fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoromethoxy-d2-5-methoxybenzyl)acetamide:a deuterium-substituted radioligand for peripheral benzodiazepine receptor","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Synthesis and evaluation of N-(5-fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoromethoxy-d2-5-methoxybenzyl)acetamide:a deuterium-substituted radioligand for peripheral benzodiazepine receptor"}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2006-06-08"},"publish_date":"2006-06-08","publish_status":"0","recid":"44203","relation_version_is_last":true,"title":["Synthesis and evaluation of N-(5-fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoromethoxy-d2-5-methoxybenzyl)acetamide:a deuterium-substituted radioligand for peripheral benzodiazepine receptor"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-16T00:18:13.338390+00:00"}