CN1183275A - 一种噻唑烷衍生物的制药应用 - Google Patents

一种噻唑烷衍生物的制药应用 Download PDF

Info

Publication number
CN1183275A
CN1183275A CN97122518A CN97122518A CN1183275A CN 1183275 A CN1183275 A CN 1183275A CN 97122518 A CN97122518 A CN 97122518A CN 97122518 A CN97122518 A CN 97122518A CN 1183275 A CN1183275 A CN 1183275A
Authority
CN
China
Prior art keywords
chemical compound
formula
pharmaceutically acceptable
acid
alkyl
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
Application number
CN97122518A
Other languages
English (en)
Other versions
CN1063942C (zh
Inventor
C·R·普尔
R·S·罗曼
M·D·布赖特威尔
A·W·特伦帕
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Ltd
SmithKline Beecham Corp
Original Assignee
SmithKline Beecham Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=10721461&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CN1183275(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd
Publication of CN1183275A publication Critical patent/CN1183275A/zh
Application granted granted Critical
Publication of CN1063942C publication Critical patent/CN1063942C/zh
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • 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
    • 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
    • A61P9/12—Antihypertensives

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Nutrition Science (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Thiazole And Isothizaole Compounds (AREA)

Abstract

本申请提供了5－[4－[2－(N－甲基－N－(2－吡啶基)氨基)乙氧基]苄基]噻唑烷－2,4－二酮马来酸盐在制备治疗和/或预防高脂血症、高血压,尤其是动脉粥样硬化、心血管疾病和某些饮食紊乱的药物中的应用。

Description

一种噻唑烷衍生物的制药应用
本申请是申请日为1993年9月4日、申请号为93119067.3的中国专利申请的分案申请。
本发明公开了某些新的化合物，这些化合物的制备方法，含有这些化合物的药物组合物以及这些化合物和组合物在医学上的应用。公开号为0,306,228的欧洲专利申请，描述了某些具有降血糖和降低血脂质活性(hypoglycaemic and hypolipidaemic activity)的噻唑烷二酮衍生物。
现在惊奇地发现EP-A-0,306,228的式(I)中特定的一组化合物具有显著的作用选择性并因此特别适用于治疗II型糖尿病。还发现这些化合物特别适用于治疗和/或预防包括高脂血症、高血压和心血管疾病，特别是动脉粥样硬化在内的其它疾病。另外，这些化合物被认为可用于治疗某些饮食紊乱，特别是可调节患有与饮食过少有关的疾病如神经性厌食症以及与饮食过多有关的疾病如肥胖症和神经性贪食症患者的食欲和食物摄入。
这些化合物显示出良好的水溶液稳定性和固体形式下良好的稳定性，这些化合物中的某些化合物被认为是特别稳定的。另外这些化合物较相应的游离碱在水中有很高的溶解度。
这些化合物惊人的和显著的稳定性和水溶解度提供了有效制剂和大量使用上的优点。
因此，本发明提供了一种式(I)化合物：
Figure A9712251800031
或其互变异构体和/或其药物上可接受的溶剂化物，其中：
R1表示氢原子，烷基，酰基，芳烷基，其中的芳基部分可被取代或未被取代，或取代或未取代的芳基；A1表示氢或1-4个选自烷基，烷氧基，芳基和卤素的任意取代基或者A1表示在相邻碳原子上的两个取代基，此取代基可与其所连接的碳原子一起形成一个取代或未取代的芳基；A2表示具有1-3个任意取代基的苯环；以及M-表示抗衡离子。
适宜的抗衡离子M-包括由药物上可接受的酸提供的离子。
适宜的抗衡离子M-源是由PKa在0.1-4.5范围内并且特别是在1.75-2.5范围内的药物上可接受的酸所提供。
优选的药物上可接受的酸包括无机酸，例如氢溴酸，盐酸和硫酸，以及有机酸，例如甲磺酸、酒石酸和马来酸，特别是酒石酸和马来酸。
优选的抗衡离子是马来酸根离子HOOC.CH＝CH.COO-。
优选A1是氢。
基团A2的适宜的任意取代基包括至多三个选自卤素、已被取代或被未取代的烷基或烷氧基的取代基。
优选地是，A2表示式(e)基团：
Figure A9712251800041
其中R2和R3分别表示氢，囟素，已被取代或未被取代的烷基或烷氧基。
较适宜地是，R2和R3分别表示氢、卤素、烷基或烷氧基。优选地是，R2和R3分别表示氢。较适宜地是，R1表示氢、烷基、酰基、特别是乙酰基、或苄基。优选地是，R1表示烷基，例如甲基。式(I)中基团：优选是下式基团：
Figure A9712251800052
其中A1和R1如上定义。
优选的式(I)化合物是5-[4-[2-(N-甲基-N-(2-吡啶基)氨基)乙氧基]苄基]噻唑烷-2，4-二酮马来酸盐。
式(I)化合物是盐。本发明涉及此盐的所有形式包括成盐氢与分子的所有可能成盐部分缔合形成的盐并且特别是与吡啶上的氮缔合形成的盐。
如上所述，式(I)化合物可以以几种互变异构体形式的一种形式存在，所有这些互变异构体均包括在本发明内。可以理解地是本发明包括式(I)化合物的所有异构体形式及其药物上可接受的盐，包括以单一异构体或构体混合物形式的任何立体异构体。
此处所用术语“芳基”包括被至多5个，优选至多3个取代基任意取代的苯基和萘基，取代基选自卤素、烷基、苯基、烷氧基、卤代烷基、羟基、硝基、烷氧羰基、烷氧羰基烷基、烷基羰氧基或烷基羰基。
此处所用术语“卤素”指氟、氯、溴和碘；优选氯。
包括烷基本身和其它基团的烷基部分(如烷氧基)的适宜烷基为直链或支链的C1-C12烷基，特别是C1-C6烷基，例如甲基、乙基，正丙基，异丙基，正丁基，异丁基或叔丁基。
对任一烷基适宜的取代基包括上述与术语“芳基”有关的取代基。
适宜的酰基包括烷基羰基。
适宜的药物上可接受的溶剂化物包括水合物。
另外，本发明还提供了式(I)化合物或其互变异构体，和/或其药物上可接受的溶剂化物的制备方法，此方法包括将式(II)化合物：
Figure A9712251800061
其中R1、A1和A2如式(I)中定义，与上述定义的抗衡离子M-源反应，此后如果需要，制备其药物上可接受的溶剂化物。
适宜的抗衡离子M-源是药物上可接受的酸。
适宜的抗衡离子M-源包括PKa在1.5-4.5范围内，特别是在1.75-2.5范围内的药物上可接受的酸。
优选的药物上可接受的酸包括无机酸如氢溴酸，盐酸和硫酸，以及有机酸如甲磺酸，酒石酸和马来酸。
优选的抗衡离子源是马来酸。
式(I)化合物与抗衡离子M-源之间的反应通常是在常规成盐条件下进行，例如，在溶剂中通常为C1-C4链烷醇溶剂如乙醇，于可提供生成所需化合物的适宜速率的任意温度下，通常于升高的温度例如溶剂的回流温度下，较适宜地是以约等摩尔量但优选用稍过量的抗衡离子M-源的情况下将式(I)化合物与抗衡离子M-源混合并然后结晶出所需产物。
式(I)化合物的药物上可接受的溶剂化物可以用常规的化学方法制备。
式(II)化合物可根据EP-A-0306228所述方法制备。
适宜的抗衡离子源是公知的在商业上可获得的，例如马来酸，或者可以根据已知方法制备所需的抗衡离子源。
式(I)化合物和其药物上可接受的盐的适宜的异构体形式可用常规化学方法以单一异构体形式制得。
本发明化合物的稳定性可以用常规定量分析法测定；例如固体形式的化合物稳定性可用加速的稳定性试验来测定，例如差示扫描量热法(DSC)，热解重量分析法(TGA)和于升温下的等温线试验。此试验包括常规贮藏试验。(其中在公知期间内于温度和湿度控制条件下贮藏试验化合物)。试验化合物的定量分析是在贮藏期之前、贮藏期间或贮藏期之后。相对于适宜的参考标准测定试验化合物的稳定性。
如上所述，本发明化合物与相应的游离碱相比在水中有显著的溶解性。这样测定本发明化合物于水溶液中的稳定性的常规方法包括在已知的温度条件和已知的期间内测定由试验化合物的水溶液中沉淀出母体游离碱的程度，我们发现式(I)化合物显示出良好的水溶液稳定性。特别是其中M-表示马来酸根或酒石酸根的式(I)化合物在水溶液中特别稳定，更惊奇地是，其中M-表示马来酸根离子。HOOC.CH＝CH.COO-的式(I)化合物在水溶液中异常地稳定。
上述试验化合物定量分析试验可以用常规方法，通常用色谱法例如高压液相色谱法进行。
如上所述，本发明的化合物具有实用的治疗活性。
因此，本发明提供了用作治疗活性物质的式(I)化合物和/或其药物上可接受的溶剂化物。
这样，本发明提供了用于治疗和/或预防高血糖症的式(I)化合物或其互变异构体和/或其药物上可接受的溶剂化物。
另外，本发明还提供了用于治疗和/或预防高脂血症的式(I)化合物或其互变异构体和/或其药物上可接受的溶剂化物。
如上所述，本发明还提供了用于治疗高血压、心血管疾病和某些饮食紊乱的式(I)化合物或其互变异构体和/或其药物上可接受的溶剂化物。
心血管疾病特别是包括动脉粥样硬化。
某些饮食紊乱特别是包括调节患有与饮食过少有关的疾病如神经性厌食症以及与饮食过多有关的疾病如肥胖症和神经性贪食症患者的食欲和食物摄入。
式(I)化合物或其互变异构体和/或其药物上可接受的溶剂化物可以以其自身的形式施用，优选地是也可以含有药物上可接受的载体的药物组合物的形式施用。
因此，本发明还提供了一种含有式(I)化合物或其互变异构体或其药物上可接受的溶剂化物和药物上可接受的载体的药物组合物。
此处所用术语“药物上可接受的”包括对人和兽医两者使用的化合物、组合物和组分，例如，术语“药物上可接受的盐”包括兽医上可接受的盐。
如果需要，组合物可以进行包装，上面附有书写或印制的使用说明。
尽管组合物也可以经其它途径例如注射和经皮吸收施用，但本发明药物组合物通常采用口服。
特别适宜的口服药物组合物是单位剂型的组合物例如片剂和胶囊，也可以使用其它混合的单位剂型如在小药囊中的粉剂。
根据常规的药物上的惯例，载体可包括稀释剂、填充剂、崩解剂、润湿剂、润滑剂、着色剂、调味剂或其它常规添加剂。
典型的载体包括例如微晶纤维素、淀粉、淀粉乙醇酸钠、聚乙烯吡咯烷酮、聚乙烯聚吡咯烷酮、硬脂酸镁或十二烷基磺酸钠。
最适宜的组合物是配制成单位剂型。此单位剂型通常含有0.1-1000mg，通常为0.1-500mg，更具体的是0.1-250mg范围内的活性成分。
本发明还提供了一种治疗和/或预防人或非人的哺乳动物高血糖症的方法，此方法包括给所需治疗的高血糖症患者或非人的哺乳动物施用无毒而有效量的式(I)化合物或其互变异构体和/或其药物上可接受的溶剂化物。
本发明进一步提供了一种治疗人或非人的哺乳动物的高脂血症的方法，此方法包括给所需治疗的高脂血症患者或非人的哺乳动物施用无毒而有效量的式(I)化合物或其互变异构体和/或其药物上可接受的溶剂化物。
通常，活性成分可以以上述的药物组合物形式施用并构成了本发明特殊的一个方面。
在治疗和/或预防高血糖症患者，和/或治疗和/或预防高脂血症患者时，可以例如以如上所述的剂量服用式(I)化合物或其互变异构体和/或其药物上可接受的溶剂化物，对70kg成年人每日一至六次服用的总日剂量通常在0.1-6000mg，更通常为1-1500mg的范围内。
在治疗和/或预防高血糖症的非人哺乳动物，特别是狗时，通常可以以每日一次或两次并以约0.025mg/kg-25mg/kg的量，例如0.1mg/kg-20mg/kg口服活性成分。相似的剂量也适用于治疗和/或预防非人哺乳动物的高脂血症。
治疗高血压，心血管疾病和饮食紊乱的剂量通常如上述高血糖症中所述。
本发明进一步提供了式(I)化合物或其互变异构体和/或其药物上可接受的溶剂化物在生产治疗和/或预防高血糖症的药物中的应用。
本发明还提供了式(I)化合物或其互变异构体和/或其药物上可接受的溶剂化物在生产治疗和/或预防高脂血症、高血压、心血管疾病或某些饮食紊乱的药物中的应用。
下列实施例用于说明本发明，但没有任何限制作用。实施例1
5-[4-[2-(N-甲基-N-(2-吡啶基)氨基)乙氧基]苄基]噻唑烷-2，4-二酮，马来酸盐。
将5-[4-[2-(N-甲基-N-(2-吡啶基)氨基)乙氧基]苄基]噻唑烷-2，4-二酮(470g)和马来酸(137g)溶于沸腾的乙醇(4l)中。此热溶液经硅藻土过滤，然后于温和搅拌下缓慢冷却，于0-5℃的冰箱中静置数小时，滤出马来酸盐，用乙醇洗涤并于50°真空中干燥，得446g(73％)产物，m.p.120-121℃。
1HNMRδ(d6-DMSO)：3.0-3.35(2H，多重峰)；3.10(3H，单峰)；3.95(2H，三重峰)；4.15(2H，三重峰)；4.85(1H，多重峰)；6.20(2H，单峰)；6.65(1H，三重峰)；6.85(3H，多重峰)；7.15(2H，双峰)；7.65(1H，三重峰)；8.05(1H，多重峰)；11.85-12.1(1H，宽峰，用D2O交换)。
在2-5ppm范围内可察到一个很宽的信号它被认为是溶剂中残存的水和可交换的羧酸质子。实施例2
5-[4-[2-(N-甲基-N-(2-吡啶基)氨基)乙氧基]苄基]噻唑烷-2，4-二酮，马来酸盐。
将5-[4-[2-(N-甲基-N-(2-吡啶基)氨基)乙氧基]苄基]噻唑烷-2，4-二酮，马来酸盐(294.6g，0.825M)和马来酸(95.8g，0.825M)于回流的乙醇(2.7l)中搅拌直至固体全部溶解。加入脱色碳并将此热溶液经塞力特硅藻土过滤，搅拌下令其冷至室温。于0-5℃冰箱中静置数小时，将标题化合物过滤，将集并于50℃真空干燥过夜，得364.1g(87％)产物，m.p.119-119.5℃。
1HNMR谱如实施例1。

Claims (2)

1.5-[4-[2-(N-甲基-N-(2-吡啶基)氨基)乙氧基]苄基]噻唑烷-2，4-二酮马来酸盐在制备治疗和/或预防高脂血症、高血压、心血管疾病和某些饮食紊乱的药物中的应用。
2.根据权利要求1的应用，其中所述的马来酸盐是用于制备治疗和/或预防心血管疾病中的动脉粥样硬化的药物中的应用。
CN97122518A 1992-09-05 1997-10-30 一种噻唑烷衍生物的制药应用 Expired - Lifetime CN1063942C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB929218830A GB9218830D0 (en) 1992-09-05 1992-09-05 Novel compounds
GB9218830.9 1992-09-05

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
CN93119067A Division CN1040323C (zh) 1992-09-05 1993-09-04 噻唑烷衍生物

Publications (2)

Publication Number Publication Date
CN1183275A true CN1183275A (zh) 1998-06-03
CN1063942C CN1063942C (zh) 2001-04-04

Family

ID=10721461

Family Applications (4)

Application Number Title Priority Date Filing Date
CN93119067A Expired - Lifetime CN1040323C (zh) 1992-09-05 1993-09-04 噻唑烷衍生物
CN97122520A Expired - Lifetime CN1066939C (zh) 1992-09-05 1997-10-30 含噻唑烷衍生物的药物组合物及其制法
CN97122518A Expired - Lifetime CN1063942C (zh) 1992-09-05 1997-10-30 一种噻唑烷衍生物的制药应用
CN97122519A Expired - Lifetime CN1051312C (zh) 1992-09-05 1997-10-30 一种噻唑烷衍生物及其制药应用

Family Applications Before (2)

Application Number Title Priority Date Filing Date
CN93119067A Expired - Lifetime CN1040323C (zh) 1992-09-05 1993-09-04 噻唑烷衍生物
CN97122520A Expired - Lifetime CN1066939C (zh) 1992-09-05 1997-10-30 含噻唑烷衍生物的药物组合物及其制法

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN97122519A Expired - Lifetime CN1051312C (zh) 1992-09-05 1997-10-30 一种噻唑烷衍生物及其制药应用

Country Status (38)

Country Link
US (1) US5910592A (zh)
EP (2) EP0960883A1 (zh)
JP (5) JP2828777B2 (zh)
KR (3) KR100371297B1 (zh)
CN (4) CN1040323C (zh)
AP (1) AP513A (zh)
AT (1) ATE182147T1 (zh)
AU (1) AU674880B2 (zh)
BR (1) BR1100916A (zh)
CA (2) CA2143849C (zh)
CY (1) CY2138B1 (zh)
CZ (2) CZ287473B6 (zh)
DE (2) DE69325658T2 (zh)
DK (1) DK0658161T3 (zh)
ES (1) ES2133410T3 (zh)
FI (2) FI106263B (zh)
GB (1) GB9218830D0 (zh)
GR (1) GR3030794T3 (zh)
HK (1) HK1012363A1 (zh)
HU (2) HU0500355D0 (zh)
IL (1) IL106904A (zh)
LU (1) LU90712I2 (zh)
MA (1) MA22970A1 (zh)
MX (1) MX9305397A (zh)
MY (1) MY111190A (zh)
NL (1) NL300035I2 (zh)
NO (4) NO303016B1 (zh)
NZ (1) NZ255505A (zh)
PL (1) PL173725B1 (zh)
RU (3) RU2128179C1 (zh)
SA (1) SA93140245B1 (zh)
SG (2) SG83747A1 (zh)
SI (1) SI9300452B (zh)
SK (1) SK280777B6 (zh)
TW (1) TW385309B (zh)
UA (1) UA41901C2 (zh)
WO (1) WO1994005659A1 (zh)
ZA (1) ZA936509B (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102532122A (zh) * 2010-12-29 2012-07-04 开封制药(集团)有限公司 酒石酸罗格列酮的制备方法
CN111818973A (zh) * 2018-02-13 2020-10-23 朱利亚尼股份公司 用于预防和治疗毛发生长紊乱的组合物

Families Citing this family (106)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9308487D0 (en) * 1993-04-23 1993-06-09 Smithkline Beecham Plc Novel compounds
US5889025A (en) * 1996-05-06 1999-03-30 Reddy's Research Foundation Antidiabetic compounds having hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
US5801173A (en) * 1996-05-06 1998-09-01 Dr. Reddy's Research Foundation Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
ZA973848B (en) * 1996-05-06 1997-12-02 Reddy Research Foundation Novel heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them.
US5919782A (en) * 1996-05-06 1999-07-06 Dr. Reddy's Research Foundation Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
BR9711098B1 (pt) * 1996-07-01 2011-10-04 compostos heterocìclicos, processo para sua preparação e composições farmacêuticas contendo os mesmos e seu uso no tratamento de diabetes e doenças relacionadas.
US6372750B2 (en) 1996-07-01 2002-04-16 Dr. Reddy's Research Foundation Heterocyclic compounds, process for their preparation and pharmaceutical compounds containing them and their use in the treatment of diabetes and related diseases
US6114526A (en) * 1996-07-01 2000-09-05 Dr. Reddy's Research Foundation Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
USRE39266E1 (en) * 1996-07-01 2006-09-05 Dr. Reddy's Laboratories, Limited Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
US5885997A (en) * 1996-07-01 1999-03-23 Dr. Reddy's Research Foundation Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
WO1998002159A1 (en) * 1996-07-12 1998-01-22 Smithkline Beecham Plc Novel treatment of leptine resistance
GB9711683D0 (en) * 1997-06-05 1997-08-06 Smithkline Beecham Plc Composition
WO1998057634A1 (en) * 1997-06-18 1998-12-23 Smithkline Beecham Plc Treatment of diabetes with thiazolidinedione and metformin
UA67743C2 (uk) * 1997-06-18 2004-07-15 Смітклайн Бічам П.Л.С. Фармацевтична композиція, що містить тіазолідиндіон і сульфонілсечовину, для лікування діабету
GB9715306D0 (en) * 1997-07-18 1997-09-24 Smithkline Beecham Plc Novel method of treatment
US20020006939A1 (en) * 1997-10-13 2002-01-17 Smithkline Beecham P.L.C. Use of thiazolidinediones for the treatment of hyperglycaemia
GB9721693D0 (en) * 1997-10-13 1997-12-10 Smithkline Beecham Plc Novel treatment
US20010031776A1 (en) * 1997-10-13 2001-10-18 Smithkline Beecham P.L.C. Use of thiazolidinediones for the treatment of hyperglycaemia
GB9721692D0 (en) * 1997-10-13 1997-12-10 Smithkline Beecham Plc Novel treatment
US7091359B2 (en) 1997-11-04 2006-08-15 Smithkline Beecham Plc Process for the preparation of thiazolidinedione derivatives
GB9723295D0 (en) * 1997-11-04 1998-01-07 Smithkline Beecham Plc Novel process
AU770817B2 (en) * 1997-12-16 2004-03-04 Smithkline Beecham Plc 5-(4-(2-(N-methyl-N-(2-pyridyl)amino)ethoxy)benzyl) thiazolidine-2,dione,maleic acid salt, hydrate as pharmaceutical
GB9726568D0 (en) * 1997-12-16 1998-02-11 Smithkline Beecham Plc Novel pharmaceutical
US6664278B2 (en) 1997-12-16 2003-12-16 Smithkline Beecham P.L.C. Hydrate of 5-[4-[2-(N-methyl-N-(2-pyridil)amino)ethoxy]benzyl]thiazolidine-2,4-dione maleic acid salt
AU774613B2 (en) * 1997-12-16 2004-07-01 Smithkline Beecham Plc Hydrate of 5-(4-(2- (N-methyl-N- (2-pyridil)amino) ethoxy)benzyl) thiazolidine-2,4-dione maleic acid salt
US20020137940A1 (en) 1997-12-16 2002-09-26 Smithkline Beecham P.L.C. 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2, 4-dione, maleic acid salt, hydrate as pharmaceutical
GB9726566D0 (en) * 1997-12-16 1998-02-11 Smithkline Beecham Plc Novel pharmaceutical
GB9726563D0 (en) * 1997-12-16 1998-02-11 Smithkline Beecham Plc Novel pharmaceutical
MA26662A1 (fr) * 1998-07-21 2004-12-20 Smithkline Beecham Plc Derives de thiazolidinedione, compositions pharmaceutiques les contenant et leur utilisation
US6613785B2 (en) 1998-07-21 2003-09-02 Smithkline Beecham Plc Use of glucose uptake enhancer for reducing post-ischemic injury of the heart
EP1516617A2 (en) * 1998-07-21 2005-03-23 SmithKline Beecham plc Use of a thiazolidinedione for reducing apoptosis of pancreatic beta cells
US20030153607A1 (en) * 1998-11-12 2003-08-14 Smithkline Beecham P.L.C. Novel composition and use
GB9824893D0 (en) * 1998-11-12 1999-01-06 Smithkline Beckman Corp Novel method of treatment
US20040102486A1 (en) * 1998-11-12 2004-05-27 Smithkline Beecham Corporation Novel method of treatment
DZ2937A1 (fr) 1998-11-12 2004-03-15 Smithkline Beecham Plc Compositions nouvelles de sensibilidants à l'insuline.
AU768994B2 (en) 1998-11-12 2004-01-15 Smithkline Beecham Plc Pharmaceutical composition for modified release of an insulin sensitiser and another antidiabetic agent
GB9909041D0 (en) * 1999-04-20 1999-06-16 Smithkline Beecham Plc Novel pharmaceutical
GB9909075D0 (en) * 1999-04-20 1999-06-16 Smithkline Beecham Plc Novel pharmaceutical
OA11873A (en) * 1999-04-23 2006-03-27 Smithkline Beecham Plc Novel pharmaceutical.
EP1173435B1 (en) * 1999-04-23 2003-07-30 SmithKline Beecham plc Polymorph of 5-[4-[2-(n-methyl-n-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione maleic acid salt
TR200103061T2 (tr) 1999-04-23 2002-05-21 Smithkline Beecham P.L.C. Yeni farmasötik madde.
US20040248945A1 (en) 1999-04-23 2004-12-09 Smithkline Beecham P.L.C. Thiazolidinedione derivative and its use as antidiabetic
TR200200438T2 (tr) * 1999-08-17 2002-05-21 Smithkline Beecham P.L.C. Tiazolidindion türevleri içeren farmasötik terkipler ve bu terkipleri hazırlama prosesi.
MY125516A (en) * 1999-11-16 2006-08-30 Smithkline Beecham Plc Novel composition based on thiazolidinedione and metformin and use
GB0006133D0 (en) * 2000-03-14 2000-05-03 Smithkline Beecham Plc Novel pharmaceutical
GB0014005D0 (en) * 2000-06-08 2000-08-02 Smithkline Beecham Plc Novel pharmaceutical
GB0014006D0 (en) * 2000-06-08 2000-08-02 Smithkline Beecham Plc Novel pharmaceutical
YU1203A (sh) * 2000-06-16 2006-05-25 Smithkline Beecham P.L.C. Lečenje i prevencija stanja vezanih za insulinsku rezistenciju srca
GB0014969D0 (en) 2000-06-19 2000-08-09 Smithkline Beecham Plc Novel method of treatment
GB0019224D0 (en) * 2000-08-04 2000-09-27 Smithkline Beecham Plc Novel pharmaceutical
AU2005229687B2 (en) * 2000-08-04 2008-03-13 Smithkline Beecham P.L.C. Tartrate salts of thiazolidinedione derivative
AU2005229688B2 (en) * 2000-08-04 2008-04-03 Smithkline Beecham P.L.C. Tartrate salts of thiazolidinedione derivative
GB0019228D0 (en) * 2000-08-04 2000-09-27 Smithkline Beecham Plc Novel pharmaceutical
GB0019223D0 (en) * 2000-08-04 2000-09-27 Smithkline Beecham Plc Novel pharmaceutical
GB0019226D0 (en) * 2000-08-04 2000-09-27 Smithkline Beecham Plc Novel pharmaceutical
GB0021785D0 (en) * 2000-09-05 2000-10-18 Smithkline Beecham Plc Novel Pharmaceutical
GB0021784D0 (en) * 2000-09-05 2000-10-18 Smithkline Beecham Plc Novel pharmaceutical
GB0021865D0 (en) * 2000-09-06 2000-10-18 Smithkline Beecham Plc Novel pharmaceutical
GB0021978D0 (en) * 2000-09-07 2000-10-25 Smithkline Beecham Plc Novel pharmaceutical
US7241895B2 (en) 2000-09-26 2007-07-10 Dr. Reddy's Laboratories Limited Polymorphic forms of 5-[4-[2-[n-methyl-n-(2-pyridyl)amino[ethoxy]benzyl] thiazolidine-2,4-dione maleate and process for their preparation
MXPA03002580A (es) * 2000-09-26 2003-10-15 Cord Janet I Nuevas formas polimorficas de maleato de 5-(4-(2-(n-metil-n-(2-piridil) amino)etoxi)bencil) tiazolidin-2, 4-diona y proceso para su preparacion.
GB0023971D0 (en) * 2000-09-29 2000-11-15 Smithkline Beecham Plc Novel pharmaceutical
EP1349855B1 (en) * 2000-12-22 2006-08-23 Smithkline Beecham Plc 5-'4-'2-(n-methyl-n- (2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2, 4-dione mesylate salt
WO2002051823A1 (en) 2000-12-26 2002-07-04 Torrent Pharmaceuticals Ltd Process for the preparation of rosiglitazone maleate
GB0127805D0 (en) 2001-11-20 2002-01-09 Smithkline Beecham Plc Pharmaceutical composition
AU2002343050A1 (en) * 2001-11-21 2003-06-10 Smithkline Beecham P.L.C. 5-(4-(2-(n-methyl-n-(2-pyridil) amino) ethoxy) benzyl) thiazolidine-2, 4-dione benzenesulfonate; process for its preparation; polymorphs i, ii and iii thereof; and its use as pharmaceutical active ingredient
KR20040062965A (ko) * 2001-11-21 2004-07-09 스미스클라인비이참피이엘시이 로시글리타존 에디실레이트 및 항당뇨제로서의 그의 용도
GB0129872D0 (en) * 2001-12-13 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
GB0129876D0 (en) * 2001-12-13 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
GB0129851D0 (en) * 2001-12-13 2002-01-30 Smithkline Beecham Plc Novel compounds
WO2003050116A1 (en) * 2001-12-13 2003-06-19 Smithkline Beecham Plc A 5(-4-(2-(n-methyl-n-(2-pyridil)amino)ethoxy)benzyl)thiazolidine-2,4-dione (i) 10-camphorsulphonic acid salt and use against diabetes mellitus
GB0129871D0 (en) * 2001-12-13 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
WO2003050112A1 (en) * 2001-12-13 2003-06-19 Smithkline Beecham Plc Toluenesulfonate hydrates of a thiazolidinedione derivative
GB0130510D0 (en) * 2001-12-20 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
GB0130509D0 (en) * 2001-12-20 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
WO2003053962A1 (en) * 2001-12-20 2003-07-03 Smithkline Beecham Plc 5- (4- (2- (n-methyl-n- (2-pyridyl) amino) ethoxy) benzyl) thiazolidine-2, 4-dione malic acid salt and use against diabetes mellitus
GB0130511D0 (en) * 2001-12-20 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
US8268352B2 (en) 2002-08-05 2012-09-18 Torrent Pharmaceuticals Limited Modified release composition for highly soluble drugs
US8216609B2 (en) 2002-08-05 2012-07-10 Torrent Pharmaceuticals Limited Modified release composition of highly soluble drugs
US7232828B2 (en) * 2002-08-10 2007-06-19 Bethesda Pharmaceuticals, Inc. PPAR Ligands that do not cause fluid retention, edema or congestive heart failure
WO2004062667A1 (en) * 2003-01-08 2004-07-29 Dr. Reddy's Laboratories Limited Amorphous form of rosiglitazone maleate and process for preparation thereof
GB0307259D0 (en) * 2003-03-28 2003-05-07 Glaxo Group Ltd Process
GB2405403A (en) * 2003-08-29 2005-03-02 Cipla Ltd Rosiglitazone maleate of particular polymorphic forms and methods of preparing rosiglitazone free base
WO2005058813A2 (en) * 2003-12-17 2005-06-30 Ranbaxy Laboratories Limited Thiodiazolidinedione, oxazolidinedione and diazolidinedione derivatives and their use as antidiabetic agents
US20050163837A1 (en) * 2003-12-31 2005-07-28 Garth Boehm Rosiglitazone formulations
EP1709038A2 (en) * 2004-01-28 2006-10-11 Usv Limited A process for the preparation of 5- 4- 2- n-methyl -n-(2-pyridyl) amino ethoxy phenyl methyl thiaz olidine-2, 4-dione maleate
GB2410948A (en) * 2004-02-13 2005-08-17 Sandoz Ag Novel phosphoric acid salt of rosiglitazone
GB2421240A (en) * 2004-12-14 2006-06-21 Sandoz Ag Phosphoric acid salt of rosiglitazone
AR047541A1 (es) * 2004-02-13 2006-01-25 Sandoz Ag Fosfato de 5-[[4-[2-metil-2-piridinil-amino-etoxi]fenil]metil]-2,4 tiazolidinadiona (rosiglitazona) y sus formas polimorficas
CZ296468B6 (cs) * 2004-06-10 2006-03-15 Zentiva, A. S. Sul kyseliny fosforecné s 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidin-2,4-dionema zpusob její prípravy
CZ296472B6 (cs) * 2004-07-27 2006-03-15 Zentiva, A. S Sul kyseliny stavelové s 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidin-2,4-dionu azpusob její prípravy a její pouzití
CZ298424B6 (cs) * 2005-05-24 2007-09-26 Zentiva, A. S. Zpusob krystalizace rosiglitazonu a jeho derivátuze smesných rozpouštedel
DE102005034406A1 (de) * 2005-07-22 2007-02-01 Ratiopharm Gmbh Neue Salze von Rosiglitazon
KR100749219B1 (ko) * 2006-03-15 2007-08-13 건일제약 주식회사 신규한 로지글리타존 옥살산염, 이의 제조방법, 및 이를포함하는 약제학적 조성물
US7435741B2 (en) 2006-05-09 2008-10-14 Teva Pharmaceutical Industries, Ltd. 2-N{5-[[4-[2-(methyl-2-pyridinylamino) ethoxy] phenyl]methyl]-2,4-thiazolidinedione} butanedioic acid, methods of preparation and compositions with rosiglitazone maleate
JP2010502670A (ja) 2006-09-07 2010-01-28 ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング 真性糖尿病のための組合せ治療
US7645616B2 (en) 2006-10-20 2010-01-12 The University Of Hong Kong Use of lipocalin-2 as a diagnostic marker and therapeutic target
EP1967182A1 (en) * 2007-03-07 2008-09-10 KRKA, tovarna zdravil, d.d., Novo mesto Pharmaceutical composition comprising a salt of rosigliatazone
US8604245B2 (en) 2007-06-04 2013-12-10 Ben-Gurion University Of The Negev Research And Development Authority Tri-aryl compounds and compositions comprising the same
CN101167726B (zh) * 2007-10-16 2011-05-18 宁夏康亚药业有限公司 马来酸罗格列酮分散片及其制备方法
PL384446A1 (pl) * 2008-02-12 2009-08-17 Adamed Spółka Z Ograniczoną Odpowiedzialnością Sól 5-[[4-[2-(metylo-2-pirydynyloamino)etoksy]fenylo]metylo]-2,4-tiazolidynodionu z kwasem malonowym i sposób jej wytwarzania
EP2184055A1 (en) 2008-11-07 2010-05-12 LEK Pharmaceuticals d.d. Process for preparing solid dosage forms of rosiglitazone maleate
DE102009053562A1 (de) 2009-11-18 2011-05-19 Alfred E. Tiefenbacher (Gmbh & Co. Kg) Rosiglitazonsuccinat enthaltende pharmazeutische Zusammensetzung
US20120094959A1 (en) 2010-10-19 2012-04-19 Bonnie Blazer-Yost Treatment of cystic diseases
CN106061940A (zh) 2013-11-05 2016-10-26 本古里安大学内盖夫研究发展局 治疗糖尿病和由其引发的并发疾病的化合物
US10034868B2 (en) 2014-11-04 2018-07-31 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the prevention and the treatment of rapidly progressive glomerulonephritis

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4197297A (en) * 1976-11-17 1980-04-08 Smithkline Corporation 6-Halo-7,8-dihydroxy-1-(hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepines
US4405211A (en) * 1980-07-29 1983-09-20 The Secretary Of State For Defence In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland Liquid crystal compositions with pleochroic anthraquinone dyes
AR240698A1 (es) * 1985-01-19 1990-09-28 Takeda Chemical Industries Ltd Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales
US5039687A (en) * 1985-12-04 1991-08-13 Hoechst-Roussel Pharmaceuticals Inc. N-(pyrrol-1-yl)pyridinamine compounds having enhancing activity
ATE186724T1 (de) * 1987-09-04 1999-12-15 Beecham Group Plc Substituierte thiazolidindionderivate
US5232925A (en) * 1987-09-04 1993-08-03 Beecham Group P.L.C. Compounds
GB8919434D0 (en) * 1989-08-25 1989-10-11 Beecham Group Plc Novel compounds
GB8919417D0 (en) * 1989-08-25 1989-10-11 Beecham Group Plc Novel compounds
GB9023583D0 (en) * 1990-10-30 1990-12-12 Beecham Group Plc Novel compounds

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102532122A (zh) * 2010-12-29 2012-07-04 开封制药(集团)有限公司 酒石酸罗格列酮的制备方法
CN102532122B (zh) * 2010-12-29 2015-12-02 开封制药(集团)有限公司 酒石酸罗格列酮的制备方法
CN111818973A (zh) * 2018-02-13 2020-10-23 朱利亚尼股份公司 用于预防和治疗毛发生长紊乱的组合物
CN111818973B (zh) * 2018-02-13 2023-08-22 朱利亚尼股份公司 用于预防和治疗毛发生长紊乱的组合物

Also Published As

Publication number Publication date
SK280777B6 (sk) 2000-07-11
DE10199002I2 (de) 2001-12-13
NL300035I2 (nl) 2001-07-02
NZ255505A (en) 1997-08-22
DE69325658D1 (de) 1999-08-19
CN1063942C (zh) 2001-04-04
CA2273147A1 (en) 1994-03-17
CN1051312C (zh) 2000-04-12
US5910592A (en) 1999-06-08
CN1066939C (zh) 2001-06-13
MA22970A1 (fr) 1994-04-01
RU98117628A (ru) 2000-08-20
CA2143849C (en) 2000-04-25
IL106904A0 (en) 1993-12-28
HU0500355D0 (en) 2005-05-30
AP9300562A0 (en) 1993-10-31
AU4973093A (en) 1994-03-29
IL106904A (en) 1997-09-30
FI982413A0 (fi) 1998-11-06
SI9300452B (sl) 2003-02-28
SI9300452A (en) 1994-06-30
HK1012363A1 (en) 1999-07-30
NO974646L (no) 1995-03-03
NO2001005I2 (no) 2004-06-01
JPH08501095A (ja) 1996-02-06
FI106263B (fi) 2000-12-29
PL173725B1 (pl) 1998-04-30
ATE182147T1 (de) 1999-07-15
NO2001006I1 (no) 2001-04-30
NO305802B1 (no) 1999-07-26
MX9305397A (es) 1995-01-31
KR20030097596A (ko) 2003-12-31
HU224212B1 (hu) 2005-06-28
HU9500659D0 (en) 1995-04-28
FI982413A (fi) 1998-11-06
PL307812A1 (en) 1995-06-26
CN1101911A (zh) 1995-04-26
NO303016B1 (no) 1998-05-18
NO950852D0 (no) 1995-03-03
AP513A (en) 1996-07-30
GR3030794T3 (en) 1999-11-30
SG48302A1 (en) 1998-04-17
JP2002047288A (ja) 2002-02-12
JP2004359676A (ja) 2004-12-24
FI951004A0 (fi) 1995-03-03
SK27795A3 (en) 1995-08-09
CN1040323C (zh) 1998-10-21
BR1100916A (pt) 2000-07-04
DK0658161T3 (da) 1999-11-29
ZA936509B (en) 1994-06-16
CZ287473B6 (en) 2000-12-13
HUT72639A (en) 1996-05-28
AU674880B2 (en) 1997-01-16
RU98117673A (ru) 2000-07-20
KR20080081099A (ko) 2008-09-05
CN1183413A (zh) 1998-06-03
KR100371297B1 (ko) 2003-05-09
UA41901C2 (uk) 2001-10-15
WO1994005659A1 (en) 1994-03-17
RU2128179C1 (ru) 1999-03-27
EP0658161B1 (en) 1999-07-14
CZ56595A3 (en) 1995-11-15
CY2138B1 (en) 2002-06-21
EP0658161A1 (en) 1995-06-21
CN1183276A (zh) 1998-06-03
DE69325658T2 (de) 1999-12-30
NO950852L (no) 1995-03-03
FI951004A (fi) 1995-03-03
NL300035I1 (nl) 2001-03-01
NO974646D0 (no) 1997-10-08
ES2133410T3 (es) 1999-09-16
CA2143849A1 (en) 1994-03-17
SA93140245B1 (ar) 2005-10-15
MY111190A (en) 1999-09-30
JP2828777B2 (ja) 1998-11-25
TW385309B (en) 2000-03-21
GB9218830D0 (en) 1992-10-21
SG83747A1 (en) 2001-10-16
JPH11147885A (ja) 1999-06-02
KR950702982A (ko) 1995-08-23
CZ290591B6 (cs) 2002-08-14
JP2008208142A (ja) 2008-09-11
EP0960883A1 (en) 1999-12-01
RU95108329A (ru) 1996-12-20
LU90712I2 (fr) 2001-03-12

Similar Documents

Publication Publication Date Title
CN1063942C (zh) 一种噻唑烷衍生物的制药应用
US5741803A (en) Substituted thiazolidinedionle derivatives
DE69233686T2 (de) Heteoaryl-Piperidine und Piperazine und ihre Anwendung als antipsychotisches und analgetisches Mittel
CN108516958B (zh) 稠环衍生物、其制备方法、中间体、药物组合物及应用
WO1992009279A1 (en) 2-arylthiazole derivative and pharmaceutical composition containing the same
JPH10194970A (ja) 置換チアゾリジンジオン誘導体を含む抗高脂血剤
CN1065460A (zh) 衍生于苯并咪唑的新的非镇静抗组胺剂
CN1159305C (zh) 新的2-(n-氰基亚氨基)噻唑烷-4-酮衍生物
JPH032173A (ja) 新規化合物、その製法及びそれを含む医薬組成物
DE69024843T2 (de) Rhodanin-Derivate und pharmazeutische Zusammensetzungen
CN108558851B (zh) 一种香豆素-噁唑-乙烯型α-葡萄糖苷酶抑制剂及其制备方法和应用
JPS6144881A (ja) ヒドロキシモルホリン誘導体，その製法及びそれを含む医薬組成物
US4728739A (en) Hypoglycemic thiazolidinediones
WO2006126714A1 (ja) ペルオキシソーム増殖剤活性化受容体の活性化剤
RU2342385C2 (ru) Новые кристаллические формы росиглитазона, способы их получения, фармацевтическая композиция и способ лечения на их основе
SK14892001A3 (sk) Monohydrát hydrochloridu 5-[4-[2-(N-metyl-N-(2-pyridyl)amino) etoxy]benzyl]tiazolidín-2,4-diónu, spôsob jeho prípravy, farmaceutický prostriedok s jeho obsahom a jeho použitie
CN1443186A (zh) 用于糖尿病治疗的噻唑烷二酮盐
CN113354616B (zh) 二芳基-1,2,4-三唑类化合物及其制法和药物用途
WO2020177752A1 (zh) 1,2,4-三唑类化合物及其制法和药物用途
JPH10503172A (ja) 新しい１，１−ビス（ヘテロアゾリル）アルカン誘導体および神経保護剤としてのその使用
JP2001206891A (ja) ホスホン酸ジエステル誘導体
CN116535361A (zh) 取代羟基嘧啶类黄嘌呤氧化酶抑制剂及其制法和药物用途
KR20240109240A (ko) 베타 아드레날린 작용제 및 이의 사용 방법
JP2001206890A (ja) ホスホン酸ジエステル誘導体

Legal Events

Date Code Title Description
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C06 Publication
PB01 Publication
C14 Grant of patent or utility model
GR01 Patent grant
C17 Cessation of patent right
CX01 Expiry of patent term

Expiration termination date: 20130904

Granted publication date: 20010404