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2012 Fiscal Year Final Research Report

Medicinal scientific study based on imiosugar C-glycosides mimics

Research Project

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Project/Area Number 22590104
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Drug development chemistry
Research InstitutionTohoku Pharmaceutical University

Principal Investigator

TAKAHATA Hiroki  東北薬科大学, 薬学部, 教授 (00109109)

Project Period (FY) 2010 – 2012
Keywordsイミノ糖 / α-グリコシダーゼ阻害剤 / 糖尿病 / L型糖
Research Abstract

Glycosidases and glycosyltransferases are involved in a wide range of anabolic and catabolic process, including digestion, the lysosomal catabolism of glycoconjugates, glycoprotein biosynthesis. Hence, modifying or blocking these processes in vivo using inhibitors is a topic of great interest from the therapeutic point of view. Iminosugars are sugars in which the endocyclic oxygen is replaced by a basic nitrogen atom. They are regarded as transition state mimics in certain types of enzyme reactions. This makes the field of iminosugars as carbohydrate mimics an exciting area of research. The asymmetric synthesis of α-1-C-alkyl-arabinoiminofuranoses was achieved by asymmetric allylic alkylation, RCM, and Negishi cross coupling as key reactions. Surprisingly, the L-forms showed a quite potent inhibitory activity toward rat intestinal maltase, while the activities of the D-forms were much weaker. Some of the prepared L-forms showed potent inhibitory activities towards intestinal maltase, with IC50 values comparable to those of commercial drugs such as acarbose, voglibose, and miglitol, which are used in the treatment of type 2 diabetes. Among them, the inhibitory activity towards intestinal sucrase of α-1-C-L-butylarabinoiminofuranose was quite strong towards intestinal sucrase compared to the above commercial drugs.

  • Research Products

    (30 results)

All 2013 2012 2011 2010 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (24 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] 低分子生体成分ミミック体の 創出を基盤とする創薬化学研究2013

    • Author(s)
      高畑廣紀
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 135 Pages: 575-585

    • URL

      http://dx.doi.org/10.1248/yakushi.13-00054

    • Peer Reviewed
  • [Journal Article] a-1-C-Buty1-1,4-dideoxy-1,4-imino-L-arabinit of as a Second- Generation Iminosugar-Based Oral a-Glucosidase Inhibitor for Improving Postprandial Hyperglycemia2012

    • Author(s)
      Kato, A.; Hayashi, E.; Miyauchi, S.; Adachi, I.; Imahori, T.; Natori, Y.; Yoshimura, Y.; Nash, R. J.; Shimaoka, H.; Nakagome, I.; Koseki, J.; Hirono, S.; Takahata, H
    • Journal Title

      J. Med. Chem. Cz4

      Volume: 55 Pages: 10347-10362

    • DOI

      doi:10.1021/im301304e

    • Peer Reviewed
  • [Journal Article] Synthesis of 1-Alkyl-2-deoxyiminofuranoses via The Iridium- catalyzed Intramolecular Cyclization of an Allylic Carbonate2012

    • Author(s)
      Natori, Y.; Kikuchi, S.; Yuichi, Y.; Kato, A.; Adachi, I.; Takahata, H. Asymmetric
    • Journal Title

      Heterocycles

      Volume: 86 Pages: 1401-1417.

    • DOI

      doi:10.3987/COM-12-S(N)99

    • Peer Reviewed
  • [Journal Article] The synthesis and biological evaluation of 1-C-alkyl-L-arabinoiminofuranoses, a novel class of a -glucosidase inhibitors novel class of a -glucosidase inhibitors2011

    • Author(s)
      Natori, Y.; Imahori, T.; Murakami, Natori, Y.; Imahori, T.; Murakami, K.; Yoshimura, Y.; Nakagawa, S.; Kato, A.; Adachi, I.; Takahata, H.
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 21 Pages: 738-741

    • Peer Reviewed
  • [Presentation] α-1-C-アルキル-D-アラビノイミノ糖誘導体の触媒的不斉合成とその生物活性評価2013

    • Author(s)
      渡邉靖香、佐久間俊嘉、名取良浩、吉村祐一、佐藤香純、加藤敦、足立伊佐雄、高畑廣紀
    • Organizer
      本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-30
  • [Presentation] 1-C-n-ブチル-L-イミノフラノース誘導体の触媒的不斉合成2013

    • Author(s)
      佐久間俊嘉,渡邉はるか,名取良浩,吉村祐一,中川進平,加藤敦,足立伊佐雄,高畑廣紀
    • Organizer
      本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-30
  • [Presentation] Cl位に4-アリールブチル基を導入したL-アラビノイミノ糖誘導体の不斉合成と生物活性評価2013

    • Author(s)
      名取良浩,今堀龍志,吉村祐一,島田陽介,加藤敦、足立伊佐雄、高畑廣紀
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-30
  • [Presentation] 次世代型イミノ糖であるα-1-C-alkyl-LABの特性と生物活性について(第2報)2013

    • Author(s)
      加藤敦、林恵利奈、足立伊佐雄、今堀龍志、名取良浩、吉村祐一、島岡秀行、中込泉,小関準、広野修一、高畑廣紀
    • Organizer
      日本薬学会第133年会、本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-30
  • [Presentation] 次世代型イミノ糖であるα-1-C-alkyl-LABの特性と生物活性について(第1報)2013

    • Author(s)
      足立伊佐雄、加藤敦、林恵利奈、中川進平、名取良浩、吉村祐一、高畑廣紀
    • Organizer
      日本薬学会第133年会、本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-30
  • [Presentation] Synthesis of 1-C-Substituted-L-arabinoiminofuranoses and Evaluation of Biological Activities as Novel Class of a-Glucosidase Inhibitors2012

    • Author(s)
      Natori, Y.; Yoshimura, Y.; Kato, A.; Adachi, I.; Hirono, S.; Takahata, H
    • Organizer
      13th Tetrahedron Symposium Asia Edition
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      2012-11-30
  • [Presentation] Cl位に4-アリールブチル基を組み込んだL-アラビノイミノフラノースの触媒的不斉合成と生物活性評価2012

    • Author(s)
      名取良浩、吉村祐一、高畑廣紀、嶋田陽介、加藤敦、足立伊佐雄
    • Organizer
      第38回反応と合成の進歩シンポジウム
    • Year and Date
      2012-11-06
  • [Presentation] L-アラビノイミノフラノースをべ-スとした食後過血糖改善薬のデザイン合成研究2012

    • Author(s)
      加藤敦、林恵利奈、中川進平、足立伊佐雄、中込泉、小関準、広野修一、名取良浩、今堀龍志、吉村祐一、高畑廣紀
    • Organizer
      第31回糖質学会年会
    • Place of Presentation
      鹿児島
    • Year and Date
      2012-09-20
  • [Presentation] The Synthesis of 1-C-Alkyl-L- arabinoiminofuranoses as Novel Class of a-Glucosidase Inhibitors2012

    • Author(s)
      Natori, Y.; Imahori, T.; Yoshimura, Y.; Takahata, H
    • Organizer
      13th Belgian Organic Synthesis Symposium
    • Place of Presentation
      Leuven, Belaium
    • Year and Date
      2012-07-20
  • [Presentation] 低分子生体成分ミミック体の創出を基盤とする創薬化学研究2012

    • Author(s)
      高畑廣紀
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
  • [Presentation] lsofagomine 類のβ-glucocerebrosidaseに対する結合親和性と構造活性相関について2012

    • Author(s)
      加藤敦、中川進平、足立伊佐雄、中込泉、 広野修一、吉村祐一、高畑廣紀
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
  • [Presentation] イリジウム触媒的環化反応を用いたピロリジンアルカロイドの立体選択的合成研究2012

    • Author(s)
      菊地俊輔、近藤孝洋、名取良浩、吉村祐一、高畑廣紀
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
  • [Presentation] C1位に4一アリールブチル基を導入したL-アラビノイミノ糖誘導体の触媒的不斉合成2012

    • Author(s)
      名取良浩、今堀龍志、吉村祐一、中川進平、加藤敦、足立伊佐雄、高畑廣紀
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
  • [Presentation] β-Glucoserebrosidaseに対する1-N型イミノ糖の親和性と構造活性相関について2011

    • Author(s)
      加藤敦,小池有里子,足立伊佐雄,中込泉,広野修一,高畑廣紀
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡
    • Year and Date
      20110300
  • [Presentation] C1置換L-アラビノイミノ糖誘導体の触媒的不斉合成2011

    • Author(s)
      名取良浩、今堀龍志、吉村祐一、中川進平、加藤敦、足立伊佐雄、高畑廣紀
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡
    • Year and Date
      20110300
  • [Presentation] Adachi,1. Docking and SAR studies of D-and L-isofagomine isomers as human(3- glucocerebrosidase inhibitors2011

    • Author(s)
      Kato,A.;Miyauchi, S.;Nakagome,1.; Yoshimura, Y.;Hirono,S.;Takahara, H
    • Organizer
      8th AFMC International Medicinal Chemistry Symposium(AIMECSII)
    • Place of Presentation
      東京
    • Year and Date
      2011-12-01
  • [Presentation] Catalytic Enantioselective Synthesis and Biological Evaluation of C 1-Alkyl L-arabino- Iminofuranose Derivatives as a-Glycosidase Inhibito2011

    • Author(s)
      Natori,Y.;lmahori,T.;Murakami,K.; Yoshimura, Y.;Nakagawa, S.;Kato,A.; Adachi, L;Takahata, H.
    • Organizer
      8th AFMC International Medicinal Chemistry Symposium(AIMECSII)
    • Place of Presentation
      東京
    • Year and Date
      2011-12-01
  • [Presentation] イリジウム触媒的環化反応を鍵工程とするピロリジン誘導体の立体選択的合成2011

    • Author(s)
      菊地俊輔、名取良浩、近藤孝洋、吉村祐一、高畑廣紀
    • Organizer
      第50回日本薬学会東北支部例会
    • Place of Presentation
      仙台
    • Year and Date
      2011-10-30
  • [Presentation] C1位アルキルL-アラビノイミノフラノース誘導体の触媒的不斉合成とその生物活性評価2011

    • Author(s)
      名取良浩、今堀龍志、吉村祐一、中川進平、加藤敦、足立伊佐雄、高畑廣紀
    • Organizer
      第53回天然有機化合物討論会
    • Place of Presentation
      大阪
    • Year and Date
      2011-09-28
  • [Presentation] hori,T.;Yoshimura, Y.; Takahata, H. The Synthesis and Biological Evaluation of 1-C-Alkyl-L- arabinoiminofuranoses,ANovel Class of a-Glucosidase Inhibitors2011

    • Author(s)
      Natori,Y.;lmahori,T.;Yoshimura, Y.; Takahata, H.
    • Organizer
      22nd French- Japanese Symposium of Medicinal and Fine Chemistry
    • Place of Presentation
      Rouen, France
    • Year and Date
      2011-09-12
  • [Presentation] D-およびL-isofagomine類の合成とグリコシダーゼ阻害活性2011

    • Author(s)
      加藤敦、宮内沙織、中川進平、足立伊佐雄、中川泉、広野修一、吉村祐一、高畑廣紀
    • Organizer
      第30回日本糖質学会年会
    • Place of Presentation
      新潟
    • Year and Date
      2011-07-13
  • [Presentation] 足立伊佐雄、L-アラビノース型アルキルイミノフラノース誘導体の触媒的不斉合成と薬理活性評価2010

    • Author(s)
      高畑廣紀、今堀龍志、名取良浩、村上景一、吉村祐一、中川進平、加藤敦
    • Organizer
      第36回反応と合成の進歩シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      20101100
  • [Presentation] L-アラビノース型1-アルキルイミノフラノース誘導体の触媒的不斉合成2010

    • Author(s)
      名取良浩、今堀龍志、村上景一、吉村祐一、高畑廣紀
    • Organizer
      第49回日本薬学会東北支部大会
    • Place of Presentation
      郡山
    • Year and Date
      20101000
  • [Presentation] Synthesis of isofagomine 21nd French-Japanese Symposium of Medicinal and Fine Chemistry2010

    • Author(s)
      Hiroki Takahata
    • Place of Presentation
      京都
    • Year and Date
      20100500
  • [Remarks]

    • URL

      http://www.tohoku-pharm.ac.jp/laboratory/bunsi ya/

  • [Patent(Industrial Property Rights)] 食後過血糖改善剤、およびピロリジン型イミノ糖またはその塩2010

    • Inventor(s)
      加藤敦、足立伊佐雄、高畑廣紀、今堀龍志
    • Industrial Property Rights Holder
      富山大学
    • Industrial Property Number
      JP2010/69950
    • Filing Date
      2010-11-09
    • Overseas

URL: 

Published: 2014-08-29  

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