Development of novel class of Cdc25A inhibitor by combination of hydrophilic and hydrophobic group

• Project/Area Number: 20590110
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Tohoku University
• Principal Investigator: SHIMAZAWA Rumiko Tohoku University, 大学院・医歯薬学総合研究科, 准教授 (00411083)
• Co-Investigator(Kenkyū-buntansha): KURIYAMA Masami 長崎大学, 大学院・医歯薬学総合研究科, 准教授 (40411087)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 脱リン酸化酵素 / Cdc25A / 複素環 / 付加反応 / 触媒的付加 / フタライド

Research Abstract

Novel N-heterocyclic derivatives were designed and synthesized as a Cdc25A inhibitor. The N-heterocyclic derivatives which have long alkyl chains exhibited strong inhibitory activity toward dual-specificity phosphatase Cdc25A. In addition, efficient synthesis of 3-arylphthalides via palladium-catalyzed 1,2-addition with the novel thioether-imidazolinium carbene ligands was successfully achieved.

Research Products

• [Journal Article] Palladium-Imidazolinium Carbene-Catalyzed Arylation of Aldehydes with Arylboronic Acids in Water (2010)
  • Author(s): Kuriyama, M.; Ishiyama, N.; Shimazawa, R.; Onomura, O.
  • Journal Title: Tetrahedron 66(34) Pages: 6814-6819
  • NAID: 120006984284
  • Peer Reviewed
• [Journal Article] Palladium-Imidazolinium Carbene-Catalyzed Arylation of Aldehydes with Arylboronic Acids in Water (2010)
  • Author(s): Kuriyama, M.; Ishiyama, N.; Shimazawa, R.; Onomura, O.
  • Journal Title: Tetrahedron Volume: 66 Pages: 6814-6819
  • NAID: 120006984284
  • Peer Reviewed
• [Journal Article] Efficient Synthesis of 3-Arylphthalides using Palladium-Catalyzed Arylation of Aldehydes with Organoboronic Acids (2009)
  • Author(s): Kuriyama, M.; Ishiyama, N.; Shimazawa, R.; Shirai, R.; Onomura, O.
  • Journal Title: J. Org. Chem. 74(23) Pages: 9210-9213
  • Peer Reviewed
• [Journal Article] Efficient Synthesis of 3-Arylphthalides using Palladium-Catalyzed Arylation of Aldehydes with Organoboronic Acids (2009)
  • Author(s): 栗山正巳, 石山夏希, 嶋澤るみ子, 白井隆一, 尾野村治
  • Journal Title: Journal of Organic Chemistry 74 Pages: 9210-9213
  • Peer Reviewed
• [Journal Article] Palladium-Catalyzed 1,2-Addition of Potassium Aryl- and Alkenyltrifluoroborates to Aldehydes using Thioether-Imidazolinium Carbene Ligands (2008)
  • Author(s): Kuriyama, M.; Shimazawa, R.; Enomoto, T.; Shirai, R.
  • Journal Title: J. Org. Chem. 73(17) Pages: 6939-6942
  • NAID: 130006998727
  • Peer Reviewed
• [Journal Article] Design and synthesis of N-alkyl oxindolylidene acetic acids as a new class of potent Cdc25A inhibittors (2008)
  • Author(s): Shimazawa, R.; Kuriyama, M.; Shirai, R.
  • Journal Title: Bioorg. Med. Chem. Lett. 18(11) Pages: 3350-3353
  • Peer Reviewed
• [Journal Article] Design and synthesis of N-alkyl oxindolylidene acetic acids as a new class of potent Cdc25A inhibitors (2008)
  • Author(s): 嶋澤るみ子、栗山正巳、白井隆一
  • Journal Title: Bioorganic and Medicinal Chemistry Letters 18 Pages: 3350-3353
  • Peer Reviewed
• [Journal Article] Palladium-Catalyzed 1, 2-Addition of Potassium Aryl- and Alkeny Itrifluoroboiates to Aldehydes using Thioether-Imidazolinium Car bene Ligands (2008)
  • Author(s): 栗山正巳、嶋澤るみ子、榎本光伯、白井隆一
  • Journal Title: Journal of Organic Chemistry 73 Pages: 6939-6942
  • Peer Reviewed
• [Presentation] Palladium-Imidazolinium Carbene-Catalyzed Arylation of Aldehydes with Arylboronic Acids in Water (2010)
  • Author(s): Kuriyama M.; Ishiyama N.; Shimazawa R.; Onomura O.
  • Organizer: 2010 International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Hawaii, USA
• [Presentation] Palladium-Imidazolinium Carbene-Catalyzed Arylation of Aldehydes with Arylboronic Acids in Water (2010)
  • Author(s): Kuriyama, M.; Ishiyama, N.; Shimazawa, R.; Onomura, O.
  • Organizer: International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Hawaii, USA
• [Presentation] C-S二座型配位子の開発と遷移金属触媒反応への適用 (2009)
  • Author(s): 栗山正巳
  • Organizer: 有機合成化学協会九州山口支部 有機合成化学講演会
  • Place of Presentation: 長崎
  • Year and Date: 2009-11-20
• [Presentation] Efficient Synthesis of Phthalides using Arylation of Aldehydes with Organoboronic Acids Catalyzed by Palladium/Thioether-Imidazolinium Chloride System (2009)
  • Author(s): 栗山正巳, 石山夏希, 嶋澤るみ子, 白井隆一, 尾野村治
  • Organizer: The 11^<th> International Kyoto Conferece on New Aspects of Organic Chemistry
  • Place of Presentation: リーガロイヤルホテル(京都)
  • Year and Date: 2009-11-11
• [Presentation] 含窒素複素環カルベンを基盤とするC-S二座型配位子を用いたパラジウム触媒による有機ホウ素試薬の付加反応と応用 (2009)
  • Author(s): 栗山正巳, 石山夏希, 榎本光伯, 嶋澤るみ子, 白井隆一, 尾野村治
  • Organizer: 第7回次世代を担う有機化学シンポジウム
  • Place of Presentation: 大阪大学(大阪)
  • Year and Date: 2009-07-24
• [Presentation] C-S二座型配位子-パラジウム錯体を用いたアルデヒドの触媒的アリール化反応 (2009)
  • Author(s): 栗山正巳
  • Organizer: 第3回万有若手交流合宿セミナー
  • Place of Presentation: 唐津
• [Presentation] Efficient Synthesis of Phthalides using Arylation of Aldehydes with Organoboronic Acids Catalyzed by Palladium/Thioether-Imidazolinium Chloride System (2009)
  • Author(s): Kuriyama M.; Ishiyama N.; Shimazawa R.; Shirai R.; Onomura O.
  • Organizer: The 11^<th> International Kyoto Conferece on New Aspects of Organic Chemistry
  • Place of Presentation: Kyoto, Japan
• [Presentation] 含窒素複素環カルベンを基盤とするC-S二座型配位子を用いたパラジウム触媒による有機ホウ素試薬の付加反応と応用 (2009)
  • Author(s): 栗山正巳, 石山夏希, 榎本光伯, 嶋澤るみ子, 白井隆一, 尾野村治
  • Organizer: 第7回次世代を担う有機化学シンポジウム
  • Place of Presentation: 大阪
• [Presentation] C-S二座配位子-パラジウム触媒を用いた有機三フッ化ホウ素塩のアルデヒドへの付加反応 (2008)
  • Author(s): 栗山正巳、嶋澤るみ子、榎本光伯、白井隆一
  • Organizer: 第34回反応と合成の進歩シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-11-04
• [Presentation] C-S二座配位子-パラジウム触媒を用いた有機三フッ化ホウ素塩のアルデヒドへの付加反応 (2008)
  • Author(s): 栗山正巳, 嶋澤るみ子, 榎本光伯, 白井隆一
  • Organizer: 第58回日本薬学会近畿支部大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-10-25
• [Presentation] C-S二座配位子-パラジウム触媒を用いた有機三フッ化ホウ素塩のアルデヒドへの付加反応 (2008)
  • Author(s): 栗山正巳、嶋澤るみ子、榎本光伯、白井隆一
  • Organizer: 第58回日本薬学会近畿支部総会・大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-10-25
• [Presentation] C-S二座配位子-パラジウム触媒を用いた有機三フッ化ホウ素塩のアルデヒドへの付加反応 (2008)
  • Author(s): 栗山正巳, 嶋澤るみ子, 榎本光伯, 白井隆一
  • Organizer: 第34回反応と合成の進歩シンポジウム
• [Presentation] Efficient 1,2-Addition of Organoboronic Acids to Aldehydes Catalyzed by the Palladium/Thioether-Imidazolinium Chloride System (2008)
  • Author(s): Kuriyama M.; Shimazawa R.; Shirai R.
  • Organizer: The Fifth International Symposium on Integrated Synthesis
  • Place of Presentation: Kobe, Japan