JPWO2010024108A1 - インフルエンザウイルス感染症の予防ないし治療剤 - Google Patents
インフルエンザウイルス感染症の予防ないし治療剤 Download PDFInfo
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- JPWO2010024108A1 JPWO2010024108A1 JP2010526641A JP2010526641A JPWO2010024108A1 JP WO2010024108 A1 JPWO2010024108 A1 JP WO2010024108A1 JP 2010526641 A JP2010526641 A JP 2010526641A JP 2010526641 A JP2010526641 A JP 2010526641A JP WO2010024108 A1 JPWO2010024108 A1 JP WO2010024108A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
Description
項1.式I:
(式中、R1は炭素数14〜24の直鎖又は分岐を有するアシル基を示す。R2はOH、NH2、NR3R4、置換または非置換のアルコキシ基、置換または非置換のアリールオキシ基、置換または非置換のアラルキルオキシ基を示す。R3,R4は同一または異なって、置換または非置換のアルキル基、置換または非置換のアリール基、置換または非置換のアラルキル基、アルコキシ基、水酸基が挙げられる。ただし、R3とR4は同時に水酸基、アルコキシ基となることはない。)
で示される化合物又はその薬学的に許容される塩の自己集合体。
項2.R1はステアロイル基、パルミトイル基、オレオイル基またはパルミトオレオイル基を示す、項1に記載の自己集合体。
項3.R2はOHまたはNH2を示す、項1に記載の自己集合体。
項4.R1はステアロイル基を示し、R2はOHまたはNH2を示す、項1に記載の自己集合体。
項5.前記自己集合体が凍結乾燥物の形態である、項1〜4のいずれかに記載の自己集合体。
項6.項1〜5のいずれかに記載の自己集合体を含むインフルエンザウイルスの感染症の予防又は治療剤。
項7.インフルエンザウイルスがH1亜型、H3亜型、H5亜型またはH7亜型である、項6に記載の予防又は治療剤。
項8.インフルエンザウイルスがH1亜型またはH3亜型インフルエンザウイルスである、項6に記載の予防又は治療剤。
項9.インフルエンザウイルスがH1亜型インフルエンザウイルスである、項6に記載の予防又は治療剤。
項10.式I:
(式中、R1はステアロイル基を示し、R2はNH2を示す。)
で示される化合物又はその薬学的に許容される塩、もしくはその自己集合体。
項11.式I:
(式中、R1は炭素数14〜24の直鎖又は分岐を有するアシル基を示す。R2はOH、NH2、NR3R4、置換または非置換のアルコキシ基、置換または非置換のアリールオキシ基、置換または非置換のアラルキルオキシ基を示す。R3,R4は同一または異なって、置換または非置換のアルキル基、置換または非置換のアリール基、置換または非置換のアラルキル基、アルコキシ基、水酸基が挙げられる。ただし、R3とR4は同時に水酸基、アルコキシ基となることはない。)
で示される化合物又はその薬学的に許容される塩もしくはその自己集合体の有効量をインフルエンザウイルスに感染した患者もしくは感染する可能性のある被験体に投与することを包含する、インフルエンザウイルス感染症の予防又は治療方法。
(式中、R1は炭素数14〜24の直鎖又は分岐を有するアシル基を示す。R2はOH、NH2、NR3R4、置換または非置換のアルコキシ基、置換または非置換のアリールオキシ基、置換または非置換のアラルキルオキシ基を示す。R3,R4は同一または異なって、置換または非置換のアルキル基、置換または非置換のアリール基、置換または非置換のアラルキル基、アルコキシ基、水酸基が挙げられる。ただし、R3とR4は同時に水酸基、アルコキシ基となることはない。)
Fmoc法に従い、Fmocアミノ酸(1.4当量)とHOBt(1-ヒドロキシベンゾトリアゾール;2.5当量)、DIC(2.8当量)を用い、固相合成によりH-Gly Leu Ala Met Ala Pro Ser Val Gly His Val Arg Gln His Gly-NH2で表されるポリペプチドを合成した。得られたポリペプチドを、ペプチド合成と同様な条件下でステアリン酸(1当量)、DIC(2.8当量)、HOBt(2.5当量)を用い、DMF/DCM溶媒中で90分間反応させて、N末端のアミノ基にステアロイル基が結合した本発明の(ステアロイル)−Gly Leu Ala Met Ala Pro Ser Val Gly His Val Arg Gln His Gly-NH2で表されるポリペプチド(以下、「C18-D1」もしくは「C18-D1」とする)を合成した。精製は、C-18カラムを使用するHPLCにより行った。C18-D1が得られたことは、質量分析([M+H]+=1782.29)により確認した。
参考例1と同様にして、C18-S2(ステアロイル-ARLPRTMVHPKPAQP-NH2)、S2(ARLPRTMVHPKPAQP-NH2)、D1(GLAMAPSVGHVRQHG-NH2)を合成した。C18-S2、S2、D1が得られたことは、質量分析により確認した。
精製したC18-D1の臨界ミセル濃度(CMC)を以下のように測定した。
1μMのN-フェニル-1-ナフチルアミン(以下「NPN」と略記する)を含むPBS (pH7.5)を調製し、C18-D1のペプチドストック溶液(1 mM)を終濃度0.1, 0.3, 1.3, 10, 30 μMで系列希釈した。これらの溶液を波長350 nmで励起し、450 nmの蛍光強度(FI)を測定した。PBSのみの場合とのFIの差を縦軸に、ペプチド溶液を横軸にプロットし、高濃度および低濃度の直線の交点の時の濃度を求めた。交点の濃度(CMC)は1.3μMであった。
インフルエンザウイルスの感染の阻害をMDCK細胞上のプラークアッセイにより決定した。6ウェルプレート中のMDCK細胞は、C18-D1、S2(H-ARLPRTMVHPKPAQP-NH2)、C18-S2(ステアロイル−ARLPRTMVHPKPAQP-NH2)、D1(H-GLAMAPSVGHVRQHG-NH2)を含むインフルエンザA/PR/8/34ウイルス溶液(100−200pfu、pfuとはプラーク形成ユニット、H1N1型)0.2mL、もしくはインフルエンザA/Victria/1/75ウイルス溶液(100−200pfu、H3N2型)とインキュベートした。5%のCO2の下での37℃、30分間のインキュベーションの後、上清を除去し、細胞をPBSを用いて洗浄した。0.6%のアガロース(0.01%のO−ジエチルアミノエチルセルロースデキストラン、0.1%NaHCO3、0.01μg/mLアセチルトリプシンを含む2×MEM+BSA 2mL(1つのウェル当たり)を添加し、2日間インキュベートした。生細胞をクリスタルバイオレット溶液(20%のエタノール中1mg/mL)で染色し、プラークの数をカウントした。最高感染活性(100%)はC18-D1のない場合のプラークの数として定義した。C18-D1のIC50値(50%抑制濃度)は、log[f/(1−f)]とlog[C18-D1]、ここでfは感染活性割合である、の間のプロットから得られた。S2、C18-S2、D1のIC50値も同様に算出した。
本発明のC18-D1およびC18-S2のマウスに対するウイルスの感染阻害実験を行った。ペプチドストック溶液(2.5-7.5mM in PBS)とインフルエンザウイルス(H1N1)を含むPBS(200 pfu)を以下の容量で混合し、30分室温放置した。作製したサンプルを一匹ずつマウスの鼻腔内に50μLずつ投与した。
Claims (11)
- R1はステアロイル基、パルミトイル基、オレオイル基またはパルミトオレオイル基を示す、請求項1に記載の自己集合体。
- R2はOHまたはNH2を示す、請求項1に記載の自己集合体。
- R1はステアロイル基を示し、R2はOHまたはNH2を示す、請求項1に記載の自己集合体。
- 前記自己集合体が凍結乾燥物の形態である、請求項1〜4のいずれかに記載の自己集合体。
- 請求項1〜5のいずれかに記載の自己集合体を含むインフルエンザウイルスの感染症の予防又は治療剤。
- インフルエンザウイルスがH1亜型、H3亜型、H5亜型またはH7亜型である、請求項6に記載の予防又は治療剤。
- インフルエンザウイルスがH1亜型またはH3亜型インフルエンザウイルスである、請求項6に記載の予防又は治療剤。
- インフルエンザウイルスがH1亜型インフルエンザウイルスである、請求項6に記載の予防又は治療剤。
- 式I:
(式中、R1は炭素数14〜24の直鎖又は分岐を有するアシル基を示す。R2はOH、NH2、NR3R4、置換または非置換のアルコキシ基、置換または非置換のアリールオキシ基、置換または非置換のアラルキルオキシ基を示す。R3,R4は同一または異なって、置換または非置換のアルキル基、置換または非置換のアリール基、置換または非置換のアラルキル基、アルコキシ基、水酸基が挙げられる。ただし、R3とR4は同時に水酸基、アルコキシ基となることはない。)
で示される化合物又はその薬学的に許容される塩もしくはその自己集合体の有効量をインフルエンザウイルスに感染した患者もしくは感染する可能性のある被験体に投与することを包含する、インフルエンザウイルス感染症の予防又は治療方法。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000059932A1 (fr) * | 1999-03-31 | 2000-10-12 | Otsuka Pharmaceutical Co., Ltd. | Peptides se liant a l'hemagglutinine du virus de la grippe |
JP2002284798A (ja) * | 2001-03-27 | 2002-10-03 | Keio Gijuku | インフルエンザウイルス・ヘマグルチニン結合性ペプチド |
WO2005084694A1 (ja) * | 2004-03-09 | 2005-09-15 | Glycomedics, Inc. | インフルエンザウイルス感染抑制剤 |
JP2006101709A (ja) * | 2004-09-30 | 2006-04-20 | Glycomedics Inc | ヘマグルチニン結合ペプチド、インフルエンザウイルス感染阻害剤、リポソーム、インフルエンザ治療薬、インフルエンザ予防薬 |
JP2007145777A (ja) * | 2005-11-29 | 2007-06-14 | Glycomedics Inc | インフルエンザウイルス感染阻害方法 |
WO2007105565A1 (ja) * | 2006-03-13 | 2007-09-20 | Keio University | インフルエンザ感染阻害ペプチド、インフルエンザウイルス感染阻害剤、リポソーム、インフルエンザ予防・治療剤 |
-
2009
- 2009-08-07 WO PCT/JP2009/064012 patent/WO2010024108A1/ja active Application Filing
- 2009-08-07 JP JP2010526641A patent/JP5583017B2/ja active Active
- 2009-08-07 EP EP09809762A patent/EP2327714A4/en not_active Withdrawn
- 2009-08-07 US US13/061,370 patent/US20110152178A1/en not_active Abandoned
- 2009-08-07 CN CN2009801339180A patent/CN102137868A/zh active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000059932A1 (fr) * | 1999-03-31 | 2000-10-12 | Otsuka Pharmaceutical Co., Ltd. | Peptides se liant a l'hemagglutinine du virus de la grippe |
JP2002284798A (ja) * | 2001-03-27 | 2002-10-03 | Keio Gijuku | インフルエンザウイルス・ヘマグルチニン結合性ペプチド |
WO2005084694A1 (ja) * | 2004-03-09 | 2005-09-15 | Glycomedics, Inc. | インフルエンザウイルス感染抑制剤 |
JP2006101709A (ja) * | 2004-09-30 | 2006-04-20 | Glycomedics Inc | ヘマグルチニン結合ペプチド、インフルエンザウイルス感染阻害剤、リポソーム、インフルエンザ治療薬、インフルエンザ予防薬 |
JP2007145777A (ja) * | 2005-11-29 | 2007-06-14 | Glycomedics Inc | インフルエンザウイルス感染阻害方法 |
WO2007105565A1 (ja) * | 2006-03-13 | 2007-09-20 | Keio University | インフルエンザ感染阻害ペプチド、インフルエンザウイルス感染阻害剤、リポソーム、インフルエンザ予防・治療剤 |
Non-Patent Citations (3)
Title |
---|
PEPT. SCI., vol. 38, JPN6009044701, 2002, pages 329 - 330, ISSN: 0002743651 * |
バイオ・高分子シンポジウム講演要旨集, vol. 18, JPN6009044716, July 2008 (2008-07-01), pages 81 - 82, ISSN: 0002743649 * |
高分子学会予稿集, vol. 57, no. 1, JPN6009044697, May 2008 (2008-05-01), pages 1703 - 1, ISSN: 0002743650 * |
Also Published As
Publication number | Publication date |
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US20110152178A1 (en) | 2011-06-23 |
EP2327714A1 (en) | 2011-06-01 |
JP5583017B2 (ja) | 2014-09-03 |
WO2010024108A1 (ja) | 2010-03-04 |
EP2327714A4 (en) | 2012-04-25 |
CN102137868A (zh) | 2011-07-27 |
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