CN1794987A - 具有提高的抗炎、抗血栓形成和抗血小板活性的作为降胆固醇药的氟伐他汀、普伐他汀、西立伐他汀、阿托伐他汀和罗苏伐他汀的硝基氧基衍生物 - Google Patents
具有提高的抗炎、抗血栓形成和抗血小板活性的作为降胆固醇药的氟伐他汀、普伐他汀、西立伐他汀、阿托伐他汀和罗苏伐他汀的硝基氧基衍生物 Download PDFInfo
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- CN1794987A CN1794987A CNA2004800144981A CN200480014498A CN1794987A CN 1794987 A CN1794987 A CN 1794987A CN A2004800144981 A CNA2004800144981 A CN A2004800144981A CN 200480014498 A CN200480014498 A CN 200480014498A CN 1794987 A CN1794987 A CN 1794987A
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- chemical compound
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- pravastatin
- fluvastatin
- atorvastatin
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Abstract
Description
化合物 | IC50(μM)±sem |
普伐他汀 | >30 |
实施例1的化合物 | 2.4±0.6 |
氟伐他汀 | >30 |
实施例3的化合物 | 13.4±3.5 |
实施例4的化合物 | 8.7±3.3 |
化合物 | 浓度(μM) | iNOS(%减少vs LPS) | COX2(%减少vs LPS) |
氟伐他汀 | 10 | -14.8±5.9 | -2.8±3.7 |
实施例3中化合物 | 10 | 44.8±11.9 | 53.9±6.1 |
实施例4中化合物 | 10 | 22.4±9.6 | 19.4±6.5 |
普伐他汀 | 100 | 4.7±3.6 | 26.9±7.9 |
实施例1的化合物 | 100 | 55.2±11.8 | 74.9±4.4 |
阿托伐他汀 | 10 | 20±14 | - |
实施例7中化合物 | 10 | 45±9 | - |
化合物 | N毛细管/mm2在局部缺血的内收肌中 | N毛细管/mm2在对侧的内收肌中 |
赋形剂 | 852±32§§ | 685±38 |
普伐他汀 | 823±42 | 736±40 |
实施例1的化合物 | 1116±53§§**++ | 660±40 |
化合物 | ApoE敲除小鼠白细胞粘附性(%)(胸主动脉) |
赋形剂 | 23.4±5 |
普伐他汀 | 23.0±6 |
实施例1的化合物 | 9.3±3*# |
化合物 | 抗血栓形成活性(%)攻击前1-h | 抗血栓形成活性(%)攻击前3-h |
赋形剂 | 0 | 0 |
普伐他汀10mg/kg腹腔注射20mg/kg腹腔注射 | 1525 | 1020 |
实施例1的化合物12mg/kg腹腔注射24mg/kg腹腔注射 | 30*40* | 40*50* |
化合物 | 血小板凝聚(GFP)IC50μM | 血小板凝聚(PRP)IC50μM |
普伐他汀 | >200 | >200 |
实施例1的化合物 | 101±10 | 74±7 |
化合物 | LPS-刺激的MNC中的TF | |
活性(AU/106细胞)§ | 抗原(ng/mg蛋白) | |
赋形剂(DMSO 0.1%) | 178±36.2 | 5.0±1.1 |
普伐他汀(50μM) | 189±37.6 | 4.4±1.3 |
实施例1的化合物(50μM) | 16±4.9** | 0.65±0.11** |
Claims (24)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03101530 | 2003-05-27 | ||
EP03101530.8 | 2003-05-27 | ||
PCT/EP2004/050897 WO2004105754A1 (en) | 2003-05-27 | 2004-05-24 | Nitrooxyderivatives of fluvastatin, pravastatin, cerivastatin, atorvastatin and rosuvastatin as cholesterol-reducing agents with improved anti-inflammatory, antithrombotic and antiplatelet activity |
Publications (2)
Publication Number | Publication Date |
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CN1794987A true CN1794987A (zh) | 2006-06-28 |
CN1794987B CN1794987B (zh) | 2010-09-29 |
Family
ID=33483985
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN2004800144981A Expired - Fee Related CN1794987B (zh) | 2003-05-27 | 2004-05-24 | 具有提高的抗炎、抗血栓形成和抗血小板活性的作为降胆固醇药的氟伐他汀、普伐他汀、西立伐他汀、阿托伐他汀和罗苏伐他汀的硝基氧基衍生物 |
Country Status (23)
Country | Link |
---|---|
US (4) | US7166638B2 (zh) |
EP (1) | EP1626716B1 (zh) |
KR (1) | KR101136434B1 (zh) |
CN (1) | CN1794987B (zh) |
AR (1) | AR044561A1 (zh) |
AT (1) | ATE353214T1 (zh) |
AU (1) | AU2004243443B2 (zh) |
BR (1) | BRPI0410049A (zh) |
CA (1) | CA2527168C (zh) |
CY (1) | CY1107614T1 (zh) |
DE (1) | DE602004004652T2 (zh) |
DK (1) | DK1626716T3 (zh) |
ES (1) | ES2280978T3 (zh) |
HK (1) | HK1090295A1 (zh) |
MX (1) | MXPA05012755A (zh) |
NO (1) | NO20056152L (zh) |
NZ (1) | NZ543086A (zh) |
PL (1) | PL379019A1 (zh) |
PT (1) | PT1626716E (zh) |
RU (1) | RU2362770C2 (zh) |
SI (1) | SI1626716T1 (zh) |
WO (1) | WO2004105754A1 (zh) |
ZA (1) | ZA200509460B (zh) |
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CN101613284B (zh) * | 2009-06-26 | 2013-05-08 | 四川抗菌素工业研究所有限公司 | 洛伐他汀、辛伐他汀和辛伐他汀-6-氧化物的硝基氧基衍生物及其制备方法 |
CN104327057A (zh) * | 2014-10-17 | 2015-02-04 | 上海应用技术学院 | 多取代吲哚类他汀内酯脱水化合物及其用途 |
CN106938979A (zh) * | 2017-03-31 | 2017-07-11 | 中国医药集团总公司四川抗菌素工业研究所 | 一种no供体型他汀衍生物、制备方法和应用 |
CN107043373A (zh) * | 2017-03-31 | 2017-08-15 | 中国医药集团总公司四川抗菌素工业研究所 | 一种噁三唑类no供体型他汀衍生物及其制备方法和应用 |
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CN108114282A (zh) * | 2016-11-28 | 2018-06-05 | 北京大学第三医院 | 他汀类化合物治疗缺血性疾病的用途 |
CN110183329A (zh) * | 2019-06-19 | 2019-08-30 | 中国医药集团总公司四川抗菌素工业研究所 | 硝酸酯类no供体型他汀衍生物及其制备方法 |
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WO2006027711A2 (en) | 2004-08-26 | 2006-03-16 | Nicholas Piramal India Limited | Prodrugs and codrugs containing bio- cleavable disulfide linkers |
TW200616604A (en) | 2004-08-26 | 2006-06-01 | Nicholas Piramal India Ltd | Nitric oxide releasing prodrugs containing bio-cleavable linker |
KR20080097989A (ko) | 2006-02-03 | 2008-11-06 | 니콕스 에스. 에이. | 근위축증 치료를 위한 의약의 니트록시 유도체의 용도 |
EP1889617A1 (en) * | 2006-07-11 | 2008-02-20 | Freie Universität Berlin | Triphenyl modified 5-membered heterocycles and their use as anticancer and antiflammatory agents |
WO2008125412A1 (en) * | 2007-04-13 | 2008-10-23 | Nicox S.A. | Crystalline forms of atorvastatin 4-(nitrooxy) butyl ester |
EP2164484A1 (en) * | 2007-06-25 | 2010-03-24 | Nicox S.A. | Use of nitric oxide-releasing statins in the treatment of pulmonary arterial hypertension |
US20090226515A1 (en) * | 2008-03-04 | 2009-09-10 | Pharma Pass Ii Llc | Statin compositions |
EP2307053A2 (en) * | 2008-06-06 | 2011-04-13 | Nicox S.A. | Compositions comprising atorvastatin 4-(nitrooxy) butyl ester and a hypolipidemic drug |
US7807716B2 (en) * | 2008-09-24 | 2010-10-05 | Oral Delivery Technology Ltd. | Nitric oxide amino acid ester compound, compositions for increasing nitric oxide levels and method of use |
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JP2648897B2 (ja) * | 1991-07-01 | 1997-09-03 | 塩野義製薬株式会社 | ピリミジン誘導体 |
HU9203780D0 (en) * | 1991-12-12 | 1993-03-29 | Sandoz Ag | Stabilized pharmaceutical products of hmg-coa reductase inhibitor and method for producing them |
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IT1295694B1 (it) | 1996-11-14 | 1999-05-27 | Nicox Sa | Nitrossi derivati per la preparazione di medicamenti ad attivita antitrombinica |
IT1311923B1 (it) | 1999-04-13 | 2002-03-20 | Nicox Sa | Composti farmaceutici. |
IT1311924B1 (it) | 1999-04-13 | 2002-03-20 | Nicox Sa | Composti farmaceutici. |
IT1314184B1 (it) | 1999-08-12 | 2002-12-06 | Nicox Sa | Composizioni farmaceutiche per la terapia di condizioni di stressossidativo |
US6573385B1 (en) * | 1999-11-11 | 2003-06-03 | Biocon India Limited | Process for manufacturing simvastatin and novel intermediates thereof |
US6476235B2 (en) * | 2001-01-09 | 2002-11-05 | Warner-Lambert Company | Process for the synthesis of 5-(4-fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-2-isopropyl-4-phenyl-1H-pyrrole-3-carboxylic acid phenylamide |
US20030100493A1 (en) | 2001-07-19 | 2003-05-29 | Sol Weiss | Sublingual use of inhibitors in the biosynthesis of cholesterol |
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Cited By (14)
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CN101613284B (zh) * | 2009-06-26 | 2013-05-08 | 四川抗菌素工业研究所有限公司 | 洛伐他汀、辛伐他汀和辛伐他汀-6-氧化物的硝基氧基衍生物及其制备方法 |
CN104327057A (zh) * | 2014-10-17 | 2015-02-04 | 上海应用技术学院 | 多取代吲哚类他汀内酯脱水化合物及其用途 |
CN108114282A (zh) * | 2016-11-28 | 2018-06-05 | 北京大学第三医院 | 他汀类化合物治疗缺血性疾病的用途 |
CN108114282B (zh) * | 2016-11-28 | 2021-03-02 | 北京大学第三医院 | 他汀类化合物治疗缺血性疾病的用途 |
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CN106938979A (zh) * | 2017-03-31 | 2017-07-11 | 中国医药集团总公司四川抗菌素工业研究所 | 一种no供体型他汀衍生物、制备方法和应用 |
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