{"created":"2023-05-15T14:54:59.556174+00:00","id":74737,"links":{},"metadata":{"_buckets":{"deposit":"ac55833e-fb0c-4825-af8a-34a0b4643cbb"},"_deposit":{"created_by":1,"id":"74737","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"74737"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00074737","sets":["1"]},"author_link":["869625","869634","869626","869630","869632","869628","869631","869627","869633","869629"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"2","bibliographicPageEnd":"393","bibliographicPageStart":"383","bibliographicVolumeNumber":"27","bibliographic_titles":[{"bibliographic_title":"Bioorganic & medicinal chemistry"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Several malignant tumors and fibrotic diseases are associated with PDGFRβ overexpression and excessive signaling, making this receptor attractive for molecular targeting and imaging approaches. A series of benzo[d]imidazole-quinoline derivatives were designed and synthesized to develop radioiodinated compounds as PDGFRβ-specific imaging probes. The structure activity relationship (SAR) evaluation of the designed compounds was performed. Among them, 2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]-8-(piperazin-1-yl)quinoline (5a) and 4-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}morpholine (5d) exhibited a relatively high PDGFRβ-TK inhibitory potency, whereas iodinated 5a derivative 5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]-8-(piperazin-1-yl)quinoline (8) exhibited a superior inhibitory potency as PDGFRβ inhibitor than iodinated 5d derivative 4-{5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}morpholine (11). Furthermore, [I]8 and [I]11 were synthesized and evaluated for PDGFRβ radioligand ability, both in vitro and in vivo. Cellular uptake experiments showed that [I]8 had a higher uptake in BxPC3-luc cells as PDGFRβ-positive cells than [I]11. Incubation of [I]8 after pretreatment of PDGFRβ ligands significantly reduced the uptake of [I]8. In biodistribution experiments using tumor-bearing mice, [I]8 accumulation in the tumor 1 h postinjection was higher than that of the benzo[d]imidazol-quinoline derivative [I]IIQP, used in our previous research. These results indicate that [I]8 could be a promising PDGFRβ imaging agent. Although its clinical application requires further structural modifications, the results obtained in this research may be useful for the development of PDGFRβ-specific radioligands.","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":"30563725","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.bmc.2018.12.016","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://www.sciencedirect.com/science/article/pii/S0968089618315414","subitem_relation_type_select":"URI"}}]},"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":"Effendi, Nurmaya"}],"nameIdentifiers":[{"nameIdentifier":"869625","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Mishiro, Kenji"}],"nameIdentifiers":[{"nameIdentifier":"869626","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Takarada, Takeshi"}],"nameIdentifiers":[{"nameIdentifier":"869627","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nishii, Ryuichi"}],"nameIdentifiers":[{"nameIdentifier":"869628","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yamada, Daisuke"}],"nameIdentifiers":[{"nameIdentifier":"869629","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Shiba, Kazuhiro"}],"nameIdentifiers":[{"nameIdentifier":"869630","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kinuya, Seigo"}],"nameIdentifiers":[{"nameIdentifier":"869631","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Odani, Akira"}],"nameIdentifiers":[{"nameIdentifier":"869632","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ogawa, Kazuma"}],"nameIdentifiers":[{"nameIdentifier":"869633","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nishii, Ryuichi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"869634","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":"Design, synthesis, and biological evaluation of radioiodinated benzo[d]imidazole-quinoline derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Design, synthesis, and biological evaluation of radioiodinated benzo[d]imidazole-quinoline derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging."}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-03-15"},"publish_date":"2019-03-15","publish_status":"0","recid":"74737","relation_version_is_last":true,"title":["Design, synthesis, and biological evaluation of radioiodinated benzo[d]imidazole-quinoline derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging."],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T21:53:44.711819+00:00"}