{"created":"2023-06-19T07:25:10.605010+00:00","id":12762,"links":{},"metadata":{"_buckets":{"deposit":"3a77c9f0-22d8-4694-8170-07a3e4ec4308"},"_deposit":{"created_by":5,"id":"12762","owners":[5],"pid":{"revision_id":0,"type":"depid","value":"12762"},"status":"published"},"_oai":{"id":"oai:gifu-pu.repo.nii.ac.jp:00012762","sets":["147:200"]},"author_link":["17760","17766","17763","17767","17764","17762","17761","17765","17759"],"item_1_biblio_info_14":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2004-06-30","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"12","bibliographicPageStart":"1","bibliographicVolumeNumber":"53","bibliographic_titles":[{"bibliographic_title":"岐阜藥科大學紀要"},{"bibliographic_title":"The annual proceedings of Gifu College of Pharmacy","bibliographic_titleLang":"en"}]}]},"item_1_creator_6":{"attribute_name":"著者名(日)","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"風岡, 和憲"}],"nameIdentifiers":[{"nameIdentifier":"17759","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"佐治木, 弘尚"}],"nameIdentifiers":[{"nameIdentifier":"17760","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"廣田, 耕作"}],"nameIdentifiers":[{"nameIdentifier":"17761","nameIdentifierScheme":"WEKO"}]}]},"item_1_creator_7":{"attribute_name":"著者名よみ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"カザオカ, カズノリ"}],"nameIdentifiers":[{"nameIdentifier":"17762","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"サジキ, ヒロナオ"}],"nameIdentifiers":[{"nameIdentifier":"17763","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"ヒロタ, コウサク"}],"nameIdentifiers":[{"nameIdentifier":"17764","nameIdentifierScheme":"WEKO"}]}]},"item_1_creator_8":{"attribute_name":"著者名(英)","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"KAZAOKA, Kazunori","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"17765","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"SAJIKI, Hironao","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"17766","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"HIROTA, Kosaku","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"17767","nameIdentifierScheme":"WEKO"}]}]},"item_1_description_1":{"attribute_name":"ページ属性","attribute_value_mlt":[{"subitem_description":"P(論文)","subitem_description_type":"Other"}]},"item_1_description_11":{"attribute_name":"抄録(日)","attribute_value_mlt":[{"subitem_description":"最近、著者らの研究室で9-ベンジル-8-ヒドロキシアデニンに比較的高いインターフェロン(IFN)誘導活性を見いだした。本研究では、8-ヒドロキシアデニン誘導体の効率のよい新規合成法の開発と構造活性相関を検討した。まず、アミノマロンニトリルとイソシアネート類から鍵中間体となる2-ヒドロキシイミダゾール(3)を得、これにイミデート、グアニジン、尿素を反応させて対応する2-置換アデニン誘導体(55-59,60,79)を合成した。さらにここで得られた2-OH体(60)および2-NH_2体(79)を選択的にアルキル化し、対応するアルキル体(61-65、81-86)を合成した。また、2-アルキルチオアデニン誘導体(90-96)の合成は3とべンゾイルイソチオシアネートとの反応で得られる閉環体をS-アルキル化して得た。その結果、構造活性相関として、1)6位アミノ基および8位水酸基(あるいはチオール基)は活性発現に必須ではないが、高活性を発現するのに効果的であること、2)9位ベンジル基が活性発現に最適であること、3)2位への置換基導入が活性に極めて効果的であり、その長さは4～6原子が最適であることを明らかにした。また、2-ブトキシ-8-ヒドロキシ体などリード化合物と比較して10^4倍高い活性を有する誘導体を見いだした。","subitem_description_type":"Other"}]},"item_1_description_12":{"attribute_name":"抄録(英)","attribute_value_mlt":[{"subitem_description":"Recently, we found that 9-benzyl-8-hydroxyadenine possesses relatively potent interferon (IFN)-inducing activity as a lead compound. An efficient, general and novel method for the synthesis of 2,9-disubstituted 8-hydroxyadenines was developed to establish the structure-activity relationship (SAR) for the IFN-inducing activity. Thus, 5-amino-4-cyano-2-hydroxyimidazole (3) was prepared from aminomalononitrile and isocyanates as key intermediates. The condensation of 3 with imidates, guanidine, and urea afforded 8-hydroxyadenines (55-59, 60, 79) possessing various substituents at the 2-position. Furthermore, selective alkylation of 2-hydroxy- and 2-aminoadenines (60 and 79) successively proceeded to give the corresponding 2-alkoxy- and 2-alkylaminoadenines (61-65 and 81-86), respectively. 2-Alkylthioadenines (90-96) were prepared by an analogous reaction of 3 with benzoylisothiocyanate and subsequent S-alkylation. The imidazole is the most useful intermediate for the synthesis of various 8-hydroxyadenine derivatives. 6-Modified 8-hydroxyadenines were prepared by application for the conventional synthetic method. Remarkable features in the SAR are as follows: 1) An amino group at the 6-position and a hydroxyl (or thiol) group carrying an acidic proton at the 8-position are required to express excellent IFN-inducing activity. 2) At the 9-position, a benzyl-type substituent is essential for the activity. 3) The introduction of an appropriate chain substituent at the 2-position resulted in a remarkable increase in the activity. Optimal IFN-inducing activity is seen when the chain length of the 2-substituent is 4-6 atoms. As a result of this study, we successfully found 2-butoxy analogues (8-hydroxy or mercaptoadenines) as the most active compounds, whose potencies were 10^4-fold greater than that of the lead compound.","subitem_description_type":"Other"}]},"item_1_source_id_13":{"attribute_name":"雑誌書誌ID","attribute_value_mlt":[{"subitem_source_identifier":"AN00053514","subitem_source_identifier_type":"NCID"}]},"item_1_text_10":{"attribute_name":"著者所属(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"Laboratory of Medicinal Chemistly, Gifu Pharmaceutical Universty"},{"subitem_text_language":"en","subitem_text_value":"Laboratory of Medicinal Chemistly, Gifu Pharmaceutical Universty"},{"subitem_text_language":"en","subitem_text_value":"Laboratory of Medicinal Chemistly, Gifu Pharmaceutical Universty"}]},"item_1_text_2":{"attribute_name":"記事種別(日)","attribute_value_mlt":[{"subitem_text_value":"総説"}]},"item_1_text_3":{"attribute_name":"記事種別(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"Review"}]},"item_1_text_9":{"attribute_name":"著者所属(日)","attribute_value_mlt":[{"subitem_text_value":"岐阜薬科大学薬品化学教室"},{"subitem_text_value":"岐阜薬科大学薬品化学教室"},{"subitem_text_value":"岐阜薬科大学薬品化学教室"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2004-06-30"}],"displaytype":"detail","filename":"KJ00004100992.pdf","filesize":[{"value":"1.2 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"url":"https://gifu-pu.repo.nii.ac.jp/record/12762/files/KJ00004100992.pdf"},"version_id":"e282966f-e645-4b94-bbbf-f3c6eaba005f"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"インターフェロン誘導活性","subitem_subject_scheme":"Other"},{"subitem_subject":"8-ヒドロキシアデニン","subitem_subject_scheme":"Other"},{"subitem_subject":"8-メルカプトアデニン","subitem_subject_scheme":"Other"},{"subitem_subject":"9-ベンジルアデニン","subitem_subject_scheme":"Other"},{"subitem_subject":"構造活性相関","subitem_subject_scheme":"Other"},{"subitem_subject":"interferon-inducing activity","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"8-hydroxyadenine","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"8-mercaptoadenine","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"9-benzyladenine","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"structure-activity relationship","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"インターフェロン誘導活性を有するアデニン誘導体の合成と構造活性相関に関する研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"インターフェロン誘導活性を有するアデニン誘導体の合成と構造活性相関に関する研究"},{"subitem_title":"Synthesis and Structure-Activity Relationship of Adenine Derivatlves with Interferon Inducing Activity","subitem_title_language":"en"}]},"item_type_id":"1","owner":"5","path":["200"],"pubdate":{"attribute_name":"公開日","attribute_value":"2004-06-30"},"publish_date":"2004-06-30","publish_status":"0","recid":"12762","relation_version_is_last":true,"title":["インターフェロン誘導活性を有するアデニン誘導体の合成と構造活性相関に関する研究"],"weko_creator_id":"5","weko_shared_id":-1},"updated":"2023-06-19T09:04:31.534819+00:00"}