CN101041626A - 四氟苄基衍生物及含有其成分的药物组合物 - Google Patents
四氟苄基衍生物及含有其成分的药物组合物 Download PDFInfo
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- CN101041626A CN101041626A CNA2007100008003A CN200710000800A CN101041626A CN 101041626 A CN101041626 A CN 101041626A CN A2007100008003 A CNA2007100008003 A CN A2007100008003A CN 200710000800 A CN200710000800 A CN 200710000800A CN 101041626 A CN101041626 A CN 101041626A
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- A61P39/06—Free radical scavengers or antioxidants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/60—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in meta- or para- positions
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/64—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring the carbon skeleton being further substituted by singly-bound oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/58—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/60—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
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- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
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- C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/45—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
- C07C309/49—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
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- C07C2601/14—The ring being saturated
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Abstract
Description
%C | %H | %N | %F | %O | |
计算值 | 47.01 | 2.10 | 3.66 | 34.70 | 12.53 |
测量值 | 47.00 | 2.03 | 3.69 |
%C | %H | %N | %F | %O | |
计算值 | 43.71 | 1.71 | 6.80 | 32.36 | 15.53 |
测量值 | 43.37 | 1.68 | 6.50 |
%C | %H | %N | %F | %O | |
计算值 | 44.85 | 1.76 | 3.49 | 33.11 | 7.97 |
测量值 | 44.83 | 2.31 | 3.43 |
%C | %H | %N | %Br | %F | %O | |
计算值 | 40.38 | 1.58 | 3.14 | 17.91 | 29.81 | 7.17 |
测量值 | 44.62 | 1.57 | 3.79 |
%C | %H | %N | %F | %O | |
计算值 | 54.72 | 3.37 | 4.25 | 23.08 | 14.58 |
测量值 | 54.90 | 3.60 | 4.06 |
%C | %H | %N | %F | %O | |
计算值 | 50.41 | 2.64 | 3.53 | 33.48 | 12.08 |
测量值 | 50.40 | 2.60 | 3.39 |
%C | %H | %N | %F | %O | |
计算值 | 48.38 | 2.54 | 3.53 | 33.48 | 12.08 |
测量值 | 47.50 | 2.20 | 3.39 |
%C | %H | %N | %F | %O | |
计算值 | 42.59 | 1.56 | 3.0 | 42.10 | 10.64 |
测量值 | 41.24 | 2.20 | 3.39 |
%C | %H | %N | %F | %O | |
计算值 | 43.65 | 2.09 | 7.27 | 28.46 | 13.69 |
测量值 | 43.68 | 2.05 | 7.26 |
%C | %H | %N | %Cl | %F | %O | |
计算值 | 42.00 | 1.89 | 3.75 | 9.49 | 35.59 | 4.28 |
测量值 | 45.23 | 1.49 | 3.74 |
%C | %H | %N | %F | %O | |
计算值 | 48.38 | 2.54 | 3.53 | 33.48 | 12.08 |
测量值 | 48.12 | 2.54 | 3.43 |
%C | %H | %N | %F | %O | |
计算值 | 48.01 | 2.37 | 3.29 | 31.27 | 15.05 |
测量值 | 48.05 | 2.39 | 3.29 |
%C | %H | %N | %F | %O | |
计算值 | 49.22 | 2.75 | 3.19 | 30.27 | 14.57 |
测量值 | 49.20 | 2.76 | 3.20 |
%C | %H | %N | %F | %O | |
计算值 | 53.56 | 3.68 | 2.84 | 26.96 | 12.97 |
测量值 | 53.58 | 3.65 | 2.85 |
Claims (20)
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KR10-2002-0034259 | 2002-06-19 | ||
KR1020020034259 | 2002-06-19 | ||
KR20020034259 | 2002-06-19 |
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CNB038167522A Division CN1309703C (zh) | 2002-06-19 | 2003-06-19 | 四氟苄基衍生物及含有其成分的用于治疗和预防中枢神经系统的急慢性神经变性疾病的药物组合物 |
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CNB038167522A Expired - Lifetime CN1309703C (zh) | 2002-06-19 | 2003-06-19 | 四氟苄基衍生物及含有其成分的用于治疗和预防中枢神经系统的急慢性神经变性疾病的药物组合物 |
CN2007100008003A Expired - Lifetime CN101041626B (zh) | 2002-06-19 | 2003-06-19 | 四氟苄基衍生物及含有其成分的药物组合物 |
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US (5) | US6927303B2 (zh) |
EP (1) | EP1551793B1 (zh) |
JP (1) | JP4113957B2 (zh) |
KR (2) | KR100545745B1 (zh) |
CN (2) | CN1309703C (zh) |
AU (1) | AU2003245070C1 (zh) |
CA (1) | CA2490120C (zh) |
DK (1) | DK1551793T3 (zh) |
ES (1) | ES2568491T3 (zh) |
HK (1) | HK1077808A1 (zh) |
WO (1) | WO2004000786A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102617383A (zh) * | 2012-03-20 | 2012-08-01 | 横店集团家园化工有限公司 | 索法地尔晶型、制备方法及包含索法地尔晶体的无菌粉末 |
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1309703C (zh) * | 2002-06-19 | 2007-04-11 | 纽若泰克有限公司 | 四氟苄基衍生物及含有其成分的用于治疗和预防中枢神经系统的急慢性神经变性疾病的药物组合物 |
KR20060121721A (ko) * | 2005-05-23 | 2006-11-29 | 주식회사 중외제약 | 테트라플루오로벤질 유도체 또는 그의 염을 함유하는주사제용 조성물 |
WO2006126846A1 (en) | 2005-05-25 | 2006-11-30 | Choongwae Pharma Corporation | Process of preparation of substituted tetrafluorobenzylaniline compound and its pharmaceutically approved salts |
KR100668111B1 (ko) * | 2005-07-28 | 2007-01-12 | (주)에스에이치제약 | 강력한 항산화 효과를 가짐으로써 급성 및 퇴행성 뇌신경계질환의 예방 및 치료에 이용 가능한 신규물질인아미노살리실산 유도체와 그 염의 제조방법 |
JP5208369B2 (ja) * | 2005-08-24 | 2013-06-12 | ニューロテック ファーマシューティカルズ カンパニー リミテッド | 神経細胞の死滅または神経機能の障害を治療するための薬学製剤及び併用療法 |
US20070298129A1 (en) * | 2005-08-24 | 2007-12-27 | Neurotech Pharmaceuticals Co., Ltd. | Compounds and compositions for treating neuronal death or neurological dysfunction |
US20070049565A1 (en) * | 2005-08-24 | 2007-03-01 | Neurotech Pharmaceuticals Co., Ltd. | Combination of cell necrosis inhibitor and lithium for treating neuronal death or neurological dysfunction |
CA2649286C (en) | 2006-04-13 | 2013-03-12 | Neurotech Co., Ltd. | 2-hydroxybenzoic acid derivatives for treating or preventing degenerative and inflammatory diseases |
KR20090013207A (ko) * | 2006-05-26 | 2009-02-04 | 페노미넘 디스커버리스 인코포레이티드 | 다발성 경화증 진단용 생물 표지자 및 그의 제조 방법 |
KR101047387B1 (ko) * | 2007-10-05 | 2011-07-08 | (주)에스에이치제약 | 뇌신경 보호를 위한 병용요법 |
AR070950A1 (es) | 2007-11-01 | 2010-05-19 | Acucela Inc | Compuestos derivados de amina, composiciones farmaceuticas de ellos, compuestos inhibidores de produccion de 11-cis-retinol y metodos para tratar enfermedades y trastornos oftalmicos |
KR100852962B1 (ko) * | 2007-11-12 | 2008-08-20 | 주식회사 뉴로테크 | 2-하이드록시-5-페닐알킬아미노벤조산 유도체 및 이의 염의제조방법 |
TWI468417B (zh) | 2007-11-30 | 2015-01-11 | Genentech Inc | 抗-vegf抗體 |
KR101523345B1 (ko) * | 2008-04-28 | 2015-05-28 | 주식회사 지엔티파마 | 재관류 손상의 치료 또는 예방용 약학 조성물 |
BRPI0919564A2 (pt) | 2008-10-22 | 2019-09-24 | Genentech Inc | modulação da degeneração do axônio |
KR101204108B1 (ko) * | 2009-02-09 | 2012-11-22 | 주식회사 지엔티파마 | 5-벤질아미노살리실산 유도체 또는 이의 염의 의약 용도 |
WO2010117170A2 (ko) | 2009-04-06 | 2010-10-14 | 주식회사 뉴로테크 | 화상 손상의 치료 또는 예방용 약학 조성물 |
ITMI20111288A1 (it) | 2011-07-11 | 2013-01-12 | Chemi Spa | Precursore farmaceutico di un principio attivo antiinfiammatorio |
CN104817465B (zh) * | 2015-04-03 | 2016-10-05 | 浙江普洛医药科技有限公司 | 索法地尔杂质a及其制备方法和应用 |
CA3027290A1 (en) | 2016-06-13 | 2017-12-21 | Syneurx International (Taiwan) Corp. | Use of lithium benzoate for treating central nervous system disorders |
CN106831462B (zh) * | 2016-12-30 | 2018-08-21 | 浙江普洛家园药业有限公司 | 索法地尔杂质b及其制备方法和应用 |
CN108164431B (zh) * | 2018-01-12 | 2021-10-08 | 浙江普洛家园药业有限公司 | 2-羟基-5-(2,3,5,6-四氟-4-三氟甲基苄氨基)苯甲酸及其制备方法 |
US20200206172A1 (en) * | 2018-12-28 | 2020-07-02 | Gnt Pharma Co., Ltd. | Compositions and methods for treating neurodegenerative disorders |
AU2021233206A1 (en) * | 2020-03-11 | 2022-10-06 | Gnt Pharma Co., Ltd. | Compositions and methods for treating reperfusion injury or hemorrhage after recanalization therapy |
CN113995723A (zh) | 2020-07-27 | 2022-02-01 | 浙江普洛家园药业有限公司 | 一种索法地尔冻干粉针剂的制备方法及其产品和用途 |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3632760A (en) * | 1969-06-25 | 1972-01-04 | Merck & Co Inc | Treatment of inflammation |
NL7008623A (zh) | 1969-06-25 | 1970-12-29 | ||
US3674844A (en) * | 1970-04-20 | 1972-07-04 | Merck & Co Inc | Salicylic acid derivatives |
JPS6056130B2 (ja) | 1978-03-20 | 1985-12-09 | 久光製薬株式会社 | 新規なサリチル酸誘導体 |
DK117484A (da) | 1983-03-14 | 1984-09-15 | Carpibem | 1-(2-carbethoxy-4-benzalkylamido-phenoxy)-3-amino-2-propanoler og fremgangsmaade til fremstilling deraf samt forbindelsernes anvendelse som laegemidler |
JPS60237041A (ja) | 1984-03-02 | 1985-11-25 | Yamamoto Kagaku Kogyo Kk | 3−プロピオニルサリチル酸誘導体の製造法 |
IT1196348B (it) | 1984-11-29 | 1988-11-16 | Italfarmaco Spa | Composti ad attivita'antiinfiammatoria |
FR2688138B1 (fr) * | 1992-03-06 | 1995-05-05 | Rhone Poulenc Rorer Sa | Application de l'amino-2 trifluoromethoxy-6 benzothiazole pour obtenir un medicament destine au traitement de la sclerose laterale amyotrophique. |
ES2147759T3 (es) | 1992-12-10 | 2000-10-01 | Pfizer | Heterociclos no aromaticos sustituidos con aminometileno y uso como antagonistas de la sustancia p. |
US5434163A (en) * | 1993-05-14 | 1995-07-18 | The Medical College Of Pennsylvania | Treatment of Cryptococcus neoformans infection |
ATE344791T1 (de) | 1997-07-01 | 2006-11-15 | Warner Lambert Co | 2-(4-brom or 4-iod phenylamino)benzoesäurederivate und ihre anwendung als mek-inhibitoren |
US6310060B1 (en) * | 1998-06-24 | 2001-10-30 | Warner-Lambert Company | 2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives and their use as MEK inhibitors |
JP2000212141A (ja) * | 1999-01-13 | 2000-08-02 | Warner Lambert Co | ジアリ―ルアミン |
JP2000273041A (ja) * | 1999-01-19 | 2000-10-03 | Sankyo Co Ltd | グルタミン酸細胞毒性による神経細胞死の阻害剤 |
CN1511830A (zh) * | 1999-03-12 | 2004-07-14 | ���ָ��.Ӣ��ķҩ�﹫˾ | 作为消炎剂的化合物 |
US6136835A (en) * | 1999-05-17 | 2000-10-24 | The Procter & Gamble Company | Methods of treatment for viral infections |
AU4149400A (en) * | 2000-04-19 | 2001-10-30 | Neurotech Co Ltd | Compounds, compositions and methods for preventing neurodegeneration in acute and chronic injuries in the central nervous system |
US6964982B2 (en) | 2000-04-20 | 2005-11-15 | Neurotech Co., Ltd. | Compounds, compositions and methods for preventing neurodegeneration in acute and chronic injuries in the central nervous system |
CN1309703C (zh) * | 2002-06-19 | 2007-04-11 | 纽若泰克有限公司 | 四氟苄基衍生物及含有其成分的用于治疗和预防中枢神经系统的急慢性神经变性疾病的药物组合物 |
FR2841556B1 (fr) * | 2002-07-01 | 2007-07-20 | Centre Nat Rech Scient | Peptides ayant des proprietes antimicrobiennes et les compositions les contenant notamment pour la conservation des aliments |
KR100522188B1 (ko) * | 2003-01-20 | 2005-10-18 | 주식회사 뉴로테크 | 뉴로트로핀에 의해 유도되는 세포괴사 억제 방법 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102617383A (zh) * | 2012-03-20 | 2012-08-01 | 横店集团家园化工有限公司 | 索法地尔晶型、制备方法及包含索法地尔晶体的无菌粉末 |
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CN1668576A (zh) | 2005-09-14 |
EP1551793A4 (en) | 2007-04-04 |
US20050239896A1 (en) | 2005-10-27 |
US20080227859A1 (en) | 2008-09-18 |
US7371896B2 (en) | 2008-05-13 |
ES2568491T3 (es) | 2016-04-29 |
CN1309703C (zh) | 2007-04-11 |
HK1077808A1 (zh) | 2006-02-24 |
AU2003245070B2 (en) | 2007-08-09 |
AU2003245070A1 (en) | 2004-01-06 |
CA2490120C (en) | 2010-06-01 |
US7319160B2 (en) | 2008-01-15 |
CA2490120A1 (en) | 2003-12-31 |
US20040209957A1 (en) | 2004-10-21 |
US6927303B2 (en) | 2005-08-09 |
US20060235239A1 (en) | 2006-10-19 |
DK1551793T3 (en) | 2016-04-25 |
JP2005529972A (ja) | 2005-10-06 |
EP1551793B1 (en) | 2016-01-20 |
AU2003245070C1 (en) | 2008-02-28 |
CN101041626B (zh) | 2010-08-25 |
KR20030097706A (ko) | 2003-12-31 |
US20070078183A1 (en) | 2007-04-05 |
WO2004000786A1 (en) | 2003-12-31 |
EP1551793A1 (en) | 2005-07-13 |
KR100545745B1 (ko) | 2006-01-24 |
US7189878B2 (en) | 2007-03-13 |
JP4113957B2 (ja) | 2008-07-09 |
KR20050105433A (ko) | 2005-11-04 |
US7511074B2 (en) | 2009-03-31 |
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