JPH11507646A - 疾患の予防及び治療のための酸化防止剤として有用な合成触媒遊離基スカベンジャー - Google Patents
疾患の予防及び治療のための酸化防止剤として有用な合成触媒遊離基スカベンジャーInfo
- Publication number
- JPH11507646A JPH11507646A JP9502272A JP50227297A JPH11507646A JP H11507646 A JPH11507646 A JP H11507646A JP 9502272 A JP9502272 A JP 9502272A JP 50227297 A JP50227297 A JP 50227297A JP H11507646 A JPH11507646 A JP H11507646A
- Authority
- JP
- Japan
- Prior art keywords
- salen
- group
- activity
- antioxidant
- metal complex
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.検出可能な核酸化活性を有し且つ次の構造式: (式中、Mは、Mn,Co,Cu,Fe,V,Cr及びNiから成る群から選択され; Aは、Cl,F,O,Br又はアセチルから成る群から選択されるアキシャルリガ ンド(axial ligand)であり; nは、0,1又は2であり; X1,X2,X3及びX4は、独立に、水素、低級アルコキシ、ハライド及びアリ ールオキシから成る群から選択され; Y1,Y2,Y3,Y4,Y5及びY6は、独立に、水素、低級アルコキシ、アリー ルオキシ、及びハライドから成る群から選択され;そして R1,R2,R3及びR4は、独立に、水素、アリール、置換されたアリール、ヘ テロ原子含有芳香族基、アリールアルキル、低級アルコキシ及びハライドから成 る群から選択され、但しR1又はR2の一方はR3又はR1の一方と共有結合して環 構造を形成していてもよい) により表わされるサレン−金属化合物。 2.図12、図19並びに図11,23,24A−24I、及び26A−26Eに 示す次の化合物:C31,C32,C33,C34,C35,C36,C37,C38,C39,C 41,C42,C43,C44,C45,C46,C47,C48,C49,C50,C51,C52,C 53,C54,C55,C56,C57,C58,C59,C60,C61,C62,C63,C64,C 65,C66,C67,C68,C69,C70,C71,C72,C73,C74,C75,C76,C 77,C78,C79,C80,C81,C82,C83,C84,C85,C86,C87,C88,C 89,C90,C91,C92,C93、及びC94から成る群から選択された構造式を有す る、請求項1に記載のサレン−金属化合物。 3.次の化合物:C41,C42,C43,C44,C45,C46,C47,C48,C49, C50,C51,C54,C55,C56,C58,C67,C68、C71,C72,C73,C74, C76,C79,C80,C81,C82,C83,C84,C85,C86、及びC87の群から選 択された構造式を有する、請求項1に記載のサレン−金属化合物。 4.図26A−26Eに示す構造X、構造XI、構造XII、構造XIV、構造XV、 構造XVI、構造XVII、構造XVIII、構造XX又は構造XXIIに従い、各構造に ついて記載される許容される置換基を有する構造式を有する、請求項1に記載サ レン−金属化合物。 5.検出可能な抗酸活性を有し、そして次の化合物:C31,C32,C33,C34 ,C35,C36,C37,C38,C39,C40,C41,C42,C43,C44,C45,C46 ,C47,C48,C49,C50,C51,C54,C55,C56,C58,C67,C68,C71 ,C72,C73,C74,C76,C79,C80,C81,C82,C83,C84,C85,C86 ,C87,C88,C89,C90,C91,C92,C93、又はC94から成る群から選択さ れる、請求項1に記載の化合物。 6.C32,C40及びC81から選択される、請求項5に記載のサレン−金属化合 物。 7.X1,X2,X3,X4,Y1及びY4の少なくとも2個が メトキシ又はハライドである、請求項1に記載のサレン−金属化合物。 8.nが0であり、そしてR1又はR2の一方がR3又はR4の一方と共有結合し て6−員環を形成している、請求項1に記載のサレン−金属化合物。 9.前記6−員環がベンゼン環又はピリジン環である、請求項8に記載のサレ ン−金属化合物。 10.抗酸化活性を有し、そして図11に示す構造式に従う構造を有し、 ここでMは、Mn,Co,Cu,Fe,V,Cr及びNiから成る群から選択され; Aは、Cl,F,O,Br又はアセチルから成る群から選択されるアキシャルリガ ンドであり; X1,X2,X3及びX4は、独立に、水素、低級アルコキシ、ハライド及びアリ ールオキシから成る群から選択され; Y1,Y2,Y3,Y4,Y5及びY6は、独立に、水素、低級アルコキシ、アリー ルオキシ及びハライドから成る群から選択され;そして Rは、1,2−エタンジイル、1,2−ベンゼンジイル、2,3−ピリジンジ イル、(2−ヒドロキシ)−2,3−プロパンジイル、1,2−エテンジイル、 1,2−エポキシエタンジイル、アルカイレンジイル及びシクロヘキサンジイル から成る群から選択され、前記基の構成員は置換されているか又は置換されてい ない、 サレン−金属錯体。 11.Rが平らな配置(plunar conformation)を有する構造である、請求項10に 記載のサレン−金属錯体。 12.検出可能な抗酸化活性を有し、そして図26A−26Eに示され 又は図11に従う構造V、構造XI、構造XII、構造XIV、構造XV、構造XVI、 構造XVII、構造XVIII、構造XX、又は構造XXIIを有し、各構造について記 載される許容される置換基を有するサレン金属化合物と賦形剤又はキャリヤーと を含んで成る医薬として許容される組成物。 13.前記サレン−金属錯体が、C31,C32,C33,,C34,C35,C36,C37 ,C38,C39,C40,C41,C42,C43,C44,C45,C46,C47,C48,C49 ,C50,C51,C54,C55,C56,C58,C67,C68,C71,C72,C73,C74 ,C76,C79,C80,C81,C82,C83,C84,C85,C86,C87,C88,C89 ,C90,C91,C92,C93、及びC94から選択される、請求項12に記載の医薬と して許容される組成物。 14.前記サレン−金属化合物がC32,C40又はC81である、請求項10に記載の 医薬として許容される組成物。 15.検出可能なスーパーオキシドジスムターゼ活性を有する、請求項1又は10 に記載のサレン−金属化合物。 16.検出可能なカタラーゼ活性を有する、請求項1又は10に記載のサレン−金 属化合物。 17.検出可能なパーオキシダーゼ活性を有する、請求項1又は10に記載のサレ ン−金属化合物。 18.検出可能なスーパーオキシドジスムターゼ、カタラーゼ及びパーオキシダ ーゼ活性を有する、請求項1又は10に記載のサレン−金属化合物。 19.錠剤、カプセル、アンプル、座薬、吸入器又は皮下シリンジ中に請求項1 又は10に記載のサレン−金属錯体を含んで成る抗酸化剤組成物。 20.酸化ストレスを有する細胞に請求項1又は10に記載のサレン −金属錯体を作用させることを含んで成る、反応性酸素種により誘導された細胞 への損傷を阻害する方法。 21.請求項1又は10の抗酸化剤サレン金属錯体を含んで成る抗酸化剤サレン− 金属錯体医薬組成物の療法的有効量を患者に投与することにより、遊離基関連疾 患状態を予防、抑制又は治療するための方法。 22.前記サレン−金属錯体がC31,C32,C33,,C34,C35,C36,C37, C38,C39,C40,C41,C42,C43,C44,C45,C46,C47,C48,C49, C50,C51,C54,C55,C56,C58,C67,C68,C71,C72,C73,C74, C76,C79,C80,C81,C82,C83,C84,C85,C86,C87,C88,C89, C90,C91,C92,C93、及びC94から成る群から選択される、請求項21に記載 の方法。 23.前記サレン−金属錯体がC32又はC40である、請求項22に記載の方法。 24.所定のスーパーオキシドジスムターゼ活性又はカタラーゼ活性を有する請 求項1又は10に記載の化合物の、疾患の治療又は予防のための使用。
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- 1996-06-06 AU AU62725/96A patent/AU6272596A/en not_active Abandoned
- 1996-06-06 CA CA002223510A patent/CA2223510C/en not_active Expired - Fee Related
- 1996-06-06 WO PCT/US1996/010037 patent/WO1996040148A1/en active Application Filing
- 1996-06-06 JP JP50227297A patent/JP4160115B2/ja not_active Expired - Fee Related
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- 1996-06-06 US US08/973,577 patent/US6046188A/en not_active Expired - Fee Related
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US20020002157A1 (en) | 2002-01-03 |
JP4160115B2 (ja) | 2008-10-01 |
WO1996040148A1 (en) | 1996-12-19 |
US20050249796A1 (en) | 2005-11-10 |
AU719450B2 (en) | 2000-05-11 |
EP0831836A1 (en) | 1998-04-01 |
US6573257B2 (en) | 2003-06-03 |
CA2223510C (en) | 2008-05-20 |
US20090311230A1 (en) | 2009-12-17 |
AU6332896A (en) | 1996-12-30 |
EP0831836A4 (en) | 2000-09-27 |
US6046188A (en) | 2000-04-04 |
US6900198B2 (en) | 2005-05-31 |
CA2223510A1 (en) | 1996-12-19 |
AU6272596A (en) | 1996-12-30 |
WO1996040149A1 (en) | 1996-12-19 |
US5696109A (en) | 1997-12-09 |
US20030216371A1 (en) | 2003-11-20 |
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