CN86100411A - 生产噻唑烷二酮的方法 - Google Patents

生产噻唑烷二酮的方法 Download PDF

Info

Publication number
CN86100411A
CN86100411A CN86100411.6A CN86100411A CN86100411A CN 86100411 A CN86100411 A CN 86100411A CN 86100411 A CN86100411 A CN 86100411A CN 86100411 A CN86100411 A CN 86100411A
Authority
CN
China
Prior art keywords
compound
gram
pyridyl
ethyl
oxyethyl group
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.)
Expired - Lifetime
Application number
CN86100411.6A
Other languages
English (en)
Other versions
CN1003934B (zh
Inventor
目黑宽同
藤田刚
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.)
Takeda Pharmaceutical Co Ltd
Original Assignee
Takeda Pharmaceutical Co 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=11683488&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CN86100411(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Takeda Pharmaceutical Co Ltd filed Critical Takeda Pharmaceutical Co Ltd
Publication of CN86100411A publication Critical patent/CN86100411A/zh
Publication of CN1003934B publication Critical patent/CN1003934B/zh
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • 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
    • 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

Abstract

式：

Description

本发明涉及新颖的噻唑烷二酮衍生物、制备这类衍生物以及用于医药领域的含有这类衍生物的抗糖尿病药剂的方法。
在临床上，使用各种双缩胍和磺酰尿衍生物作为抗糖尿病药剂。
但是，现在很少使用双缩胍类，因为双缩胍往往引起乳酸中毒;而且，虽然磺酰尿类具有很强的降血糖活性，但是使用磺酰尿类时，必须十分小心，因为它们往往造成严重的低血糖。因此，一直期待着一种新型的无这类缺点的抗糖尿病药剂。
在另一方面，在日本特许公开特开昭55-22636和特开昭55-64586以及“化学和药物公报”（Chemical    &    Pharmaceutical    Bulletion），30，第3563页（1982）;出处同上，30，第3580页（1982）和32，第2267页（1982）等文献中，提到了具有使血葡萄糖和血脂降低作用的各种噻唑烷二酮类。在“糖尿病”（Diabetes），32，第804页（1983）之中。也报道了西格利塔腙（Ciglitazone）的抗糖尿病活性。但是，这些化合物均未在实践中采用。可以提出的理由是：1）活性不足，或者/和2）有强毒性。
本发明人合成了各种在上面提到的日本特许公开说明书中未具体描述过的各种化合物，而且对其进行了研究，发现这些化合物具有潜在的药理作用，而且毒性较小。
本发明要提出一些在医疗上可以作为抗糖尿病药剂使用的化合物，这些化合物在药理作用和毒性或者不希望有的副反应之间具有很宽的安全范围。
本发明涉及：
1）（Ⅰ）式化合物
Figure 86100411_IMG4
或其药理上可接受的盐，
2）抗糖尿病药剂，其中含有（Ⅰ）式化合物或其药理上可接受的盐作为有效成分，以及
3）制备（Ⅰ）式化合物或其药理上可接受盐的方法，其中包括使下式化合物水解：
Figure 86100411_IMG5
用上面的（Ⅰ）式所表示的化合物，具体地说包括下列物质：
5-〔4-〔2-（3-乙基-2-吡啶基）乙氧基〕苄基〕-2，4-噻唑烷二酮，
5-〔4-〔2-（4-乙基-2-吡啶基）乙氧基〕苄基〕-2，4-噻唑烷二酮，
5-〔4-〔2-（5-乙基-2-吡啶基）乙氧基〕苄基〕-2，4-噻唑烷二酮，
5-〔4-〔2-（6-乙基-2-吡啶基）乙氧基〕苄基〕-2，4-噻唑烷二酮。
本发明的化合物（Ⅰ），在分子中既包含碱性氮也包含酸性氮，而且可以用适当的酸或碱在需要时使之转变成药理上可接受的盐。
这种酸的盐类，例如有无机酸盐（如盐酸盐、氢溴酸盐和硫酸盐等等）、有机酸盐（如丁二酸盐、顺丁烯二酸盐、反丁烯二酸盐、苹果酸盐和酒石酸盐等等）以及磺酸盐（例如甲磺酸盐、苯磺酸盐和甲苯磺酸盐等等）。这种碱的盐，例如有碱金属盐（如钠盐、钾盐）和碱土金属盐（如钙盐等），所有这些盐实际都用已知的方法制备。
本发明的（Ⅰ）式化合物或其药理上可接受的盐，具有降低血葡萄糖和血脂的作用，而且毒性较小;可以直接使用它们，或者以与业已知道的药理上可接受的载体、赋形剂或填料组成混合物的形式使用，以作为哺乳动物（包括人）的抗糖尿病药剂。
这种抗糖尿病药剂，通常以片剂、胶囊（包括软胶囊和微胶囊）剂、粉剂和粒剂等以进行口服投药，而且根据情况，也可以以注射液、栓剂和小丸片等形式进行非肠道投药。成年病人的口服药量最好为0.05-10mg/公斤体重/天，非肠道投药量为0.01-10mg/公斤体重/天，每天一次，或者每周分成2-4次。
由上面提到的通式（Ⅰ）所代表的化合物及其药理上可接受的盐（以下统称“化合物（Ⅰ）”），可由对（Ⅱ）式所代表的化合物进行水解的方法制备。这种水解反应，最好在适当溶剂中用无机酸的条件下进行。所用的溶剂例如有醇类（例如甲醇、乙醇、丙醇、丁醇、异丁醇和2-甲氧基乙醇等）、二甲基亚砜、二氧噻吩烷、二噁烷、四氢呋喃和二甲氧基乙烷等;所用的无机酸例如有盐酸、氢溴酸和硫酸等。水解反应的温度范围从20℃至150℃。反应时间为0.5-20小时。
所制备的上述通式为（Ⅰ）的化合物或其药理上可接受的盐可用传统的浓缩、萃取、重结晶、色层等方法进行分离和纯化。
由上面提到的通式（Ⅱ）所代表的化合物，可以通过下述反应制备：
〔其中R代表氢或者低级烷基〕。
由R所代表的低级烷基，例如是甲基、乙基、丙基、异丙基和丁基之类的C1-C4烷基。
由化合物（Ⅲ）和化合物（Ⅳ）制备化合物（Ⅴ）的反应，是在例如氢化钠存在下进行的。这个反应，可以在-10℃至30℃温度范围内，于某种溶剂中，例如在二甲基甲酰胺和四氢呋喃中进行。由化合物（Ⅴ）生成化合物（Ⅵ）的反应，很容易通过传统的催化还原。采用例如钯-碳作为催化剂来实现。可以以纯产物的形式分离化合物（Ⅵ），也可以使化合物（Ⅵ）在不分离、不提纯的条件下直接进行下一步反应。通过在氢溴酸水溶液存在下，使化合物（Ⅵ）进行重氮化，然后在铜催化剂存在下，例如氧化亚铜、氧化铜、氯化亚铜、氯化铜、溴化亚铜、溴化铜等存在下，使生成物与丙烯酸或者其低级烷基酯（Ⅶ）反应（米尔文芳基化作用，Meerwein    arylation），制备化合物（Ⅷ）。化合物（Ⅷ）可以用例如色谱法提纯，而且可以不经分离或者提纯直接进行随后的反应。
然后使化合物（Ⅷ）与硫脲反应生成化合物（Ⅱ）。这个反应通常是在醇类（例如甲醇、乙醇、丙醇、丁醇、异丁醇和α-甲氧基乙醇等）、二甲基亚砜和二氧噻吩烷等之中进行。反应温度通常为20-180℃，最好为60-150℃。所使用的硫脲量，相对于每摩尔化合物（Ⅷ）有1-2摩尔硫脲。
对于这个反应来说，在反应进行时，产生付产物溴化氢，因此为了捕获此付产物，可以在乙酸钠或乙酸钾等存在下进行此反应，其用量相对于每摩尔化合物（Ⅷ）为1-1.5摩尔。可以分离生成的化合物（Ⅱ），但是也可以不经分离直接进行水解。
本发明的化合物（Ⅰ），具有优良的使血葡萄糖和血脂降低的活性，而且毒性很低，这一点可用下列实验数据来证实。
实验例
1.小鼠体内血糖和血脂降低活性
将试验化合物（在三个剂量水平下）以CE-2粉末食物的规定食物混合物形式（CLEA日本）给雄性KKAy鼠（8-10周的鼠，每组5只）喂食，同时使之自由饮水四天。
在第五天，自鼠眼眶静脉中取出血样。
采用葡萄糖氧化酶法和使用在市场可买到的分析仪器Cleantech TG-S（Iatron，日本），分别测定血液葡萄糖和血浆甘油三酯（TG）。根据血液葡萄糖和血浆甘油三酯降低活性的剂量响应曲线，计算了每个试验化合物与对照值相比减小25%的有效剂量，作为ED25值（mg/公斤/天）。结果示于表1之中。
2.大鼠体内血脂降低活性
给雄性Sprague-Dawley大鼠（7周的大鼠，每组5只）供给实验室食物（日本，CLEA，CE-2），同时使之自由饮水。让这些鼠强制性经口投药这些试验化合物（三个剂量水平），四天投药的试验化合物均悬浮于5%的阿拉伯胶溶液中。在第五天，自大鼠尾静脉中取出血液样品。使用市场上可以买到的分析仪器Cleantech TG-S（Iatron）测定血浆甘油三酯。根据血脂降低活性的剂量响应曲线，计算了每个试验化合物的血脂减少与对照值相比为25%的有效剂量，作为ED25值（mg/公斤/天）。结果列于表1之中。
3.大鼠的两周毒性研究
给雄性和雌性Sprague-Dawley大鼠（五周的大鼠，每组五只）进食实验室食物（日本，CLEA，CE-2），同时使之自由饮水，给这些大鼠强制地经口投药试验化合物二周，每日一次，所有的试验化合物均悬浮于5%的阿拉伯胶溶液中。每个试验化合物的剂量为100mg/公斤/天。当两周投药结束后，在乙醚麻醉的条件下，使用经肝素化的注射器从腹主动脉中抽取血液样品，经过大约20小时禁食，杀死这些动物，切除肝脏和心脏，称重。使用自动细胞计数器进行血液分析。这些数据表示相对于对照值增加或者减少的%，正如表1中所示的那样。
在表1中，化合物（Ⅰ）是属于本发明范围内的一个化合物，而化合物（a）和（b）是在日本特许公开特开昭55-22636中具体提到的已知化合物。
虽然化合物（c）、（d）和（e）未在上面提到的专利申请中具体提过，但是也引证了以便于比较，因为这些化合物在其化学结构上与本发明的化合物（Ⅰ）类似。正如表1中给出的实验结果所表明的那样，本发明的化合物（Ⅰ）在降血糖和降血脂活性方面优于化合物（a）、（c）、（d）和（e），而与化合物（b）相当，和（a）、（b）、（c）、（d）和（e）化合物相比，其毒性极低。通过引入乙基所带来的上述效果完全出乎意料。因此，本发明的化合物（Ⅰ）表现有良好的降低血糖和低血脂活性，而且即使连续长时间投药的条件下对内部器官和血液的毒性均极小。所以化合物（Ⅰ）对于哺乳动物（包括人）的Ⅱ型糖尿病及其伴随的肥胖症和血脂过多症是有价值的治疗药剂。
实施例1
a）在冰冷却的条件下，将在油（16.0克）中的60%的氢化钠分批加入2-（5-乙基-2-吡啶基）乙醇（53.0克）和4-氟硝基苯（47.0克）的二甲基甲酰胺（500ml）溶液中，将此混合物在冰冷却的条件下搅拌1小时，然后在室温下搅拌30分钟，倒入水中，用乙醚萃取，用水洗涤乙醚层，经MgSO4干燥，蒸除溶剂，制得晶体状4-〔2-（5-乙基-2-吡啶基）乙氧基〕硝基苯（62.0克，产率62.9%），经乙醚-己烷重结晶后，制成无色的棱晶体，熔点53-54℃。
b）在10%Pd-c催化剂（50%湿品，6.0克）存在下，于室温和1大气压条件下，使溶解在甲醇（500ml）中的4-〔2-（5-乙基-2-吡啶基）乙氧基〕硝基苯（60.0克）的溶液氢化，过滤除去催化剂，在减压下浓缩滤液，将残留的油状物溶解在丙酮（500ml）-甲醇（200ml）之中，在此溶液中加入47%的HBγ水溶液（152克），冷却此混合物，在不高于5℃条件下，在此混合物中滴加NaNO2（17.3克）的水（30ml）溶液，5℃下将此全部混合物搅拌20分钟，然后在其中加入丙烯酸甲酯（112克），使温度提高到38℃，剧烈搅拌下，在此混合物中逐渐加入氧化亚铜（2.0克）。搅拌此混合物直至停止产生氮气为止，在减压下加以浓缩，用浓氨水碱化此浓集物，用乙酸乙酯萃取，乙酸乙酯层用水洗涤，干燥（MgSO4）。蒸发除去溶剂，残留下2-溴-3-｛4-〔2-（5-乙基-2-吡啶基）乙氧基〕苯基｝丙酸甲酯，呈原油状物（74.09克，85.7%）。红外光谱（净）Cm-1：1735。核磁共振δ（PPm）（在CDCl3中）：1.21（3H，t，J＝7），2.60（2H，q，J＝7），3.0-3.6（4H，m），3.66（3H，S），4.30（2H，t，J＝7），4.3（1H，m），6.7-7.5（6H，m），8.35（1H，d，J＝2）。
c）将在b）中得到的2-溴-3-｛4-〔2-（5-乙基-2-吡啶基）乙氧基〕苯基｝丙酸甲酯（73.0克）、硫脲（14.2克）、乙酸钠（15.3克）和乙醇（500ml）的混合物，迴流下搅拌3小时，减压下浓缩此反应混合物，用碳酸氢钠饱和水溶液中和得到的浓集物，在其中加入水（200ml）和乙醚（100ml）。将全部混合物搅拌10分钟，生成5-｛4-〔2-（5-乙基-2-吡啶基）乙氧基〕苯基｝-2-亚胺基-4-噻唑烷二酮晶体（0.3克，523.0%）。经甲醇重结晶后，得到无色棱晶体，熔点187-188℃（分解）。C19H21N3O2S的元素分析结果：
计算值：C，64.20;H，5.95;N，11.82。
测得值：C，64.20;H，5.84;N，11.73。
d）将5-｛4-〔2-（5-乙基-2-吡啶基）乙氧基〕苄基｝-2-亚胺基-4-噻唑烷二酮（23.5克）的2NHCl（200ml）溶液迴流6小时。减压下蒸除溶剂，用碳酸氢钠饱和水溶液中和此残余物。过滤收集沉淀出的晶体（23.5克，97.5%），用二甲基甲酰胺-水重结晶，制得无色针状的5-｛4-〔2-（5-乙基-2-吡啶基）乙氧基〕苄基｝-2，4-噻唑烷二酮（20.5克，86.9%），熔点为183-184℃。C19H20N2O3S的元素分析结果：
计算值：C，64.02;H，5.66;N，7.86。
测得值：C，63.70;H，5.88;N，8.01。
e）在5-｛4-〔2-（5-乙基-2-吡啶基）乙氧基〕苄基｝-2，4-噻唑烷二酮（356mg）的甲醇（10ml）的悬浮液中，加入28%甲醇钠-甲醇溶液（0.2克）以制备溶液。浓缩此溶液，用乙醚稀释至生成晶体。过滤收集这些晶体，用甲醇-乙醇重结晶，制成5-｛4-〔2-（5-乙基-2-吡啶基）乙氧基〕苄基｝-2，4-噻唑烷二酮的钠盐，是无色晶体（298mg，78.8%），熔点262-263℃（分解）。
C19H19N2O3SNa的元素分析结果：
计算值：C，60.31;H，5.06;N，7.40。
测得值：C，60.20;H，5.07;N，7.52。
实施例2
（1）5-｛4-〔2-（5-乙基-2-吡啶基）乙氧基〕苄基｝-2，4-噻唑烷二酮    100克
（2）乳糖    50克
（3）谷物淀粉    15克
（4）羧甲基纤维素钙    44克
（5）硬脂酸镁    1克
共计    210克
将（1）、（2）和（3）的总量及30克（4），用水捏和，真空干燥，然后造粒。使14克（4）和1克（5）与制得的粒状物混合，使用制片机将全部混合物制片，制得直径为8mm的药片1000片，每片含100mg（1）。
参照例1
按照实施例1-a）的步骤，制备表2中列出的化合物。
Figure 86100411_IMG8
参照例2
按照实施例1-b）制备下列化合物。
2-溴-3-｛4-〔2-（4-甲基-2-吡啶基）乙氧基〕苯基｝丙酸甲酯。红外光谱（净）Cm-1：1735。核磁共振δ（PPm，CDCl3）：2.34（3H，S），3.10（1H，dd，J＝14和7），3.25（2H，t，J＝6），3.38（1H，dd，J＝14和7），3.67（3H，S），4.29（1H，t，J＝7），4.37（2H，t，J＝6），6.8-7.5（6H，m），8.35（1H，dd，J＝5和2）。
2-溴-3-｛4-〔2-（4-甲基-2-吡啶基）乙氧基〕苯基｝-丙酸甲酯。红外光谱（净）Cm-1：1735。核磁共振δ（PPm，CDCl3）：2.30（3H，S），3.10（1H，dd，J＝14和7），3.26（3H，t，J＝7），3.37（1H，dd，J＝14和7），3.67（3H，S），4.30（3H，t，J＝7），67-7.36（6H，m），8.37（1H，d，J＝6）。
参照例3
在10%Pd-c催化剂（50%湿品，2.0克）存在下，1大气压下使溶有4-〔2-（5-甲基-2-吡啶基）乙氧基〕硝基苯（15.0克）的甲醇（150ml）溶液催化还原，滤除催化剂，浓缩滤液制得4-〔2-（5-甲基-2-吡啶基）乙氧基〕苯胺晶体（12.3克，92.5%），用乙酸乙酯-己烷重结晶，制得无色棱晶体，熔点74-75℃。
C14H16H2O的元素分析。
计算值：C，73.66;H，7.06;N，12.27。
测得值：C，73.84;H，7.17;N，12.06。
参照例4
在4-〔2-（5-甲基-2-吡啶基）乙氧基〕苯胺（12.0克）、47%的HBr水溶液（36.5克）和甲醇（40ml）-丙酮（80ml）的混合物中，在5℃或低于5℃下滴加NaNO2（4.0克）水（10ml）溶液。5℃下将全部混合物搅拌20分钟，然后在其中加入丙烯酸甲酯（27.0克），将温度提高到38℃。剧烈搅拌下，逐渐在此混合物中加入氧化亚铜（1.0克），停止产生氮气后，在减压下浓缩此反应混合物，用浓氨水碱化此浓集物，然后用乙酸乙酯萃取，用水洗涤乙酸乙酯层，干燥（MgSO4），蒸除溶剂后，残留下2-溴-3-｛4-〔2-（5-甲基-2-吡啶基）乙氧基〕苯基｝-丙酸甲酯（17.5克，87.5%），呈原油状物。红外光谱（净）Cm-1：1735。核磁共振δ（PPm，CDCl3）：2.27（3H，S），3.10（1H，dd，J＝14和7），3.22（2H，t，J＝6），3.38（1H，dd，J＝14和7），3.66（3H，S），4.29（2H，t，J＝6），4.32（1H，t，J＝7），6.7-7.5（6H，m），8.34（1H，d，J＝2）。
参照例5
按照实施例1-c）制备表3所列的化合物
Figure 86100411_IMG9
Figure 86100411_IMG10
参照例6
按照实施例1-d）制备表4中所列的化合物。
参照例7
将2-亚胺基-5-｛4-〔2-（5-甲基-2-吡啶基）乙氧基〕苄基｝-4-噻唑烷二酮（8.0克）、2NHCl（80ml）和乙醇（80ml）的混合物迴流16小时。用碳酸氢钠饱和水溶液中和此反应溶液以生成晶体，过滤收集这些晶体，用乙醇重结晶后得出5-｛4-〔2-（5-甲基-2-吡啶基）乙氧基〕苄基｝-2.4-噻唑烷二酮（7.0克，87.5%），为无色棱晶体，熔点192-193℃。
C18H18N2O3的元素分析：
计算值：C，63.14;H，5.30;N，8.18。
测得值：C，63.22;H，5.40;N，8.11。

Claims (1)

1、一种制备式为
的化合物或其药理上可接受盐的方法，其特征在于使式为
Figure 86100411_IMG3
的化合物水解。
CN86100411.6A 1985-01-19 1986-01-18 生产噻唑烷二酮的方法 Expired CN1003934B (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP8085/1985 1985-01-19
JP808585 1985-01-19

Publications (2)

Publication Number Publication Date
CN86100411A true CN86100411A (zh) 1986-07-16
CN1003934B CN1003934B (zh) 1989-04-19

Family

ID=11683488

Family Applications (1)

Application Number Title Priority Date Filing Date
CN86100411.6A Expired CN1003934B (zh) 1985-01-19 1986-01-18 生产噻唑烷二酮的方法

Country Status (28)

Country Link
US (1) US4687777A (zh)
EP (1) EP0193256B1 (zh)
JP (1) JPS61267580A (zh)
KR (1) KR920010046B1 (zh)
CN (1) CN1003934B (zh)
AR (1) AR240698A1 (zh)
AT (1) ATE41931T1 (zh)
AU (1) AU572719B2 (zh)
BR (1) BR1100325A (zh)
CA (1) CA1277323C (zh)
CS (1) CS407991A3 (zh)
DE (2) DE3662689D1 (zh)
DK (2) DK171614B1 (zh)
ES (1) ES8705886A1 (zh)
FI (1) FI81098C (zh)
GR (1) GR860124B (zh)
HK (1) HK3692A (zh)
HU (1) HU196795B (zh)
IE (1) IE58928B1 (zh)
LU (1) LU90719I2 (zh)
LV (1) LV5779B4 (zh)
MX (1) MX9202933A (zh)
MY (1) MY102016A (zh)
NL (1) NL300038I2 (zh)
NO (1) NO163857C (zh)
PT (1) PT81859B (zh)
SG (1) SG105691G (zh)
ZA (1) ZA86203B (zh)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4812570A (en) * 1986-07-24 1989-03-14 Takeda Chemical Industries, Ltd. Method for producing thiazolidinedione derivatives
CN102149669A (zh) * 2008-10-10 2011-08-10 株式会社德山 羰氧基化合物的制备方法
CN101222912B (zh) * 2005-03-30 2012-10-03 华生制药公司 包含双胍和噻唑烷二酮衍生物的药物新剂型

Families Citing this family (268)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK305884A (da) * 1983-06-24 1984-12-25 Yamanouchi Pharma Co Ltd Phenoxyderivat, fremgangsmaade til fremstilling deraf og farmaceutisk praeparat indeholdende et saadant derivat
CN1003445B (zh) * 1984-10-03 1989-03-01 武田药品工业株式会社 噻唑烷二酮衍生物，其制备方法和用途
FI91869C (fi) * 1987-03-18 1994-08-25 Tanabe Seiyaku Co Menetelmä antidiabeettisena aineena käytettävien bensoksatsolijohdannaisten valmistamiseksi
HU203330B (en) * 1987-06-10 1991-07-29 Pfizer Process for producing oxazolidin-2-one derivatives and hypoglychemic pharmaceutical compositions containing them
EP0295828A1 (en) * 1987-06-13 1988-12-21 Beecham Group Plc Novel compounds
GB8713861D0 (en) * 1987-06-13 1987-07-15 Beecham Group Plc Compounds
US4791125A (en) * 1987-12-02 1988-12-13 Pfizer Inc. Thiazolidinediones as hypoglycemic and anti-atherosclerosis agents
US4798835A (en) * 1987-12-02 1989-01-17 Pfizer Inc. dl-5-[(2-benzyl-3,4-dihydro-2H-benzopyran-6-yl)methyl]thiazolidine-2,4-dione as an anti-atherosclerosis agent
GB8820389D0 (en) * 1988-08-26 1988-09-28 Beecham Group Plc Novel compounds
GB8919417D0 (en) 1989-08-25 1989-10-11 Beecham Group Plc Novel compounds
US4997948A (en) * 1989-10-27 1991-03-05 American Home Products 5-[(1- and 2-naphthalenyl) sulfonyl]-2,4-thiazolidinediones and derivatives thereof
KR0170416B1 (ko) † 1990-02-09 1999-02-18 로버트 에이. 아미테이지 고혈압 치료를 위한 인슐린 증감제의 용도
US5356913A (en) * 1990-02-09 1994-10-18 The Upjohn Company Use of insulin sensitizing agents to treat hypertension
EP0454501B1 (en) * 1990-04-27 2001-09-05 Sankyo Company Limited Benzylidenethiazolidine derivatives, their preparation and their use for the inhibition of lipid peroxides
GB9023584D0 (en) * 1990-10-30 1990-12-12 Beecham Group Plc Novel compounds
US5158966A (en) * 1991-02-22 1992-10-27 The University Of Colorado Foundation, Inc. Method of treating type i diabetes
CA2106967C (en) * 1991-04-11 2003-12-09 Takashi Sohda Thiazolidinedione derivatives, production and use thereof
US5441971A (en) * 1991-04-11 1995-08-15 The Upjohn Company Thiazolidinedione derivatives, production and use thereof
US5183823A (en) * 1991-04-11 1993-02-02 Takeda Chemical Industries, Ltd. Pyridine n-oxide compounds which are useful as hypoglycemic and hypolipidemic agents
FR2680512B1 (fr) * 1991-08-20 1995-01-20 Adir Nouveaux derives de 2,4-thiazolidinedione, leur procede de preparation et les compositions pharmaceutiques qui les contiennent.
GB9124513D0 (en) * 1991-11-19 1992-01-08 Smithkline Beecham Plc Novel process
US5741803A (en) * 1992-09-05 1998-04-21 Smithkline Beecham Plc Substituted thiazolidinedionle derivatives
GB9218830D0 (en) * 1992-09-05 1992-10-21 Smithkline Beecham Plc Novel compounds
EP0915090A1 (en) * 1992-09-10 1999-05-12 Eli Lilly And Company Compounds useful as hypoglycemic agents and for treating Alzheimer's disease
JP2845743B2 (ja) * 1992-12-28 1999-01-13 三菱化学株式会社 新規なナフタレン誘導体
US5594016A (en) * 1992-12-28 1997-01-14 Mitsubishi Chemical Corporation Naphthalene derivatives
USRE39384E1 (en) 1993-09-01 2006-11-07 Smithkline Beecham P.L.C. Substituted thiazolidinedione derivatives
US5457109A (en) * 1993-09-15 1995-10-10 Warner-Lambert Company Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of disease states at risk for progressing to noninsulin-dependent diabetes mellitus
US6046222A (en) * 1993-09-15 2000-04-04 Warner-Lambert Company Use of thiazolidinedione derivatives in the treatment of polycystic ovary syndrome, gestational diabetes and disease states at risk for progressing to noninsulin-dependent diabetes mellitus
NZ274346A (en) * 1993-09-15 1997-06-24 Sankyo Co Use of various thiazolidine-2,4-dione and oxazolidine-2,4-dione derivatives to prevent or delay onset of non-insulin dependent diabetes mellitus
US5874454A (en) * 1993-09-15 1999-02-23 Warner-Lambert Company Use of thiazolidinedione derivatives in the treatment of polycystic ovary syndrome, gestational diabetes and disease states at risk for progressing to noninsulin-dependent diabetes mellitus
WO1995024400A1 (en) * 1994-03-08 1995-09-14 American Home Products Corporation Thiazolidinedione derivatives as anti-hyperglycemic agents
US6251928B1 (en) * 1994-03-16 2001-06-26 Eli Lilly And Company Treatment of alzheimer's disease employing inhibitors of cathepsin D
EP0787725B1 (en) * 1994-10-20 2003-04-23 Nippon Chemiphar Co., Ltd. Quinoline derivative
US5708012A (en) * 1995-04-28 1998-01-13 Sankyo Company, Limited Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of insulin resistant subjects with normal glucose tolerance in order to prevent or delay the onset of noninsulin-dependent mellitus
AU5121796A (en) * 1995-05-08 1996-11-29 Nippon Chemiphar Co. Ltd. 2,4-thiazolidinedione or oxazolidinedione derivatives and hy poglycemic agent
TW438587B (en) * 1995-06-20 2001-06-07 Takeda Chemical Industries Ltd A pharmaceutical composition for prophylaxis and treatment of diabetes
NZ286920A (en) * 1995-07-03 1997-06-24 Sankyo Co Use of combination of hmg-coa reductase inhibitors and of insulin sensitizers for the prevention/treatment of arteriosclerosis or xanthoma
EP0783888A1 (en) * 1995-12-26 1997-07-16 Sankyo Company Limited Use of troglitazone and related thiazolidinediones in the manufacture of a medicament for the treatment and prophylaxis of osteoporosis
IL120443A (en) * 1996-03-18 2000-07-16 Sankyo Co Use of an insulin sensitizer for the manufacture of a medicament for the treatment or prophylaxis of pancreatitis
US5958957A (en) * 1996-04-19 1999-09-28 Novo Nordisk A/S Modulators of molecules with phosphotyrosine recognition units
AU2381397A (en) * 1996-04-19 1997-11-12 Novo Nordisk A/S Modulators of molecules with phosphotyrosine recognition units
CA2257284C (en) * 1996-05-31 2005-10-04 Sankyo Company Limited Remedy for autoimmune diseases
US5952509A (en) * 1996-06-27 1999-09-14 Takeda Chemical Industries, Ltd. Production of benzaldehyde compounds
ATE399545T1 (de) * 1996-11-08 2008-07-15 Nippon Chemiphar Co Mittel zur verringerung der eigeweidefette
JP2001514663A (ja) * 1997-03-12 2001-09-11 エスモンド，ロバート ダブリュー． アルツハイマー病を処置または予防するための方法
US5908859A (en) * 1997-08-11 1999-06-01 Eli Lilly And Company Benzothiophenes for inhibiting hyperlipidemia
HUP9902721A2 (hu) 1997-11-25 1999-12-28 The Procter & Gamble Co. Tömény textillágyító készítmény és ehhez alkalmazható magas telítetlenségű textillágyító vegyület
GB9726568D0 (en) * 1997-12-16 1998-02-11 Smithkline Beecham Plc Novel pharmaceutical
AU1507799A (en) * 1997-12-16 1999-07-05 Sankyo Company Limited Leukemia remedy
US20040058873A1 (en) * 1998-03-12 2004-03-25 Esmond Robert W. Method for treating or preventing Alzheimer's disease
AU1740900A (en) * 1998-11-20 2000-06-13 Genentech Inc. Method of inhibiting angiogenesis
US6191154B1 (en) 1998-11-27 2001-02-20 Case Western Reserve University Compositions and methods for the treatment of Alzheimer's disease, central nervous system injury, and inflammatory diseases
TWI249401B (en) * 1999-04-14 2006-02-21 Takeda Chemical Industries Ltd Agent for improving ketosis
US6869959B1 (en) 1999-04-28 2005-03-22 Institute Of Medicinal Molecular Design Inc. Heterocyclic carboxylic acid derivatives
EP1109796A1 (en) * 1999-07-01 2001-06-27 Geron Corporation Telomerase inhibitors and methods of their use
JP2001072592A (ja) 1999-07-01 2001-03-21 Kyowa Hakko Kogyo Co Ltd テロメラーゼ阻害剤
US7390824B1 (en) * 1999-09-07 2008-06-24 Bristol-Myers Squibb Company Method for treating diabetes employing an aP2 inhibitor and combination
US6878749B2 (en) 1999-09-17 2005-04-12 Novartis Ag Method of treating metabolic disorders, especially diabetes, or a disease or condition associated with diabetes
US6559188B1 (en) 1999-09-17 2003-05-06 Novartis Ag Method of treating metabolic disorders especially diabetes, or a disease or condition associated with diabetes
AR028299A1 (es) 1999-09-17 2003-05-07 Novartis Ag Una composicion farmaceutica que comprende nateglinida, un proceso para su preparacion y el uso de dicha composicion para la preparacion de un medicamento para el tratamiento de desordenes metabolicos, especialmente diabetes, o de una enfermedad o condicion asociada con diabetes.
ES2156574B1 (es) * 1999-11-18 2002-02-01 Vita Invest Sa Nuevos derivados de tiazolidindiona como agentes antidiabeticos
RU2256661C2 (ru) 1999-12-03 2005-07-20 Киото Фармасьютикал Индастриз, Лтд. Производные тетрагидроизохинолина и их соли и фармацевтическая композиция на их основе
ATE385421T1 (de) 2000-01-21 2008-02-15 Novartis Pharma Gmbh Zusammensetzungen bestehend aus dipeptidylpeptidase-iv inhibitoren und antidiabetica
US6680387B2 (en) * 2000-04-24 2004-01-20 Aryx Therapeutics Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
US6958355B2 (en) * 2000-04-24 2005-10-25 Aryx Therapeutics, Inc. Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
EE200200601A (et) * 2000-04-25 2004-04-15 Kyorin Pharmaceutical Co., Ltd. Uus stabiilne tiasolidiindiooniderivaadi kristallja meetod selle valmistamiseks
AU2001294673A1 (en) 2000-09-21 2002-04-02 Aryx Therapeutics Isoxazolidine compounds useful in the treatment of diabetes, hyperlipidemia, andatherosclerosis
US6982251B2 (en) * 2000-12-20 2006-01-03 Schering Corporation Substituted 2-azetidinones useful as hypocholesterolemic agents
US6452014B1 (en) 2000-12-22 2002-09-17 Geron Corporation Telomerase inhibitors and methods of their use
ATE341343T1 (de) * 2000-12-26 2006-10-15 Sankyo Co Medizinische zusammensetzungen mit diuretischem und die insulinresistenz verbesserndem mittel
NZ525921A (en) * 2001-01-26 2005-06-24 Schering Corp Combinations of peroxisome proliferator-activated receptor (PPAR) activator(s) and sterol absorption inhibitor(s) and treatments for vascular indications
PT1385548E (pt) * 2001-01-26 2007-08-24 Schering Corp Combinações de um inibidor ou de inibidores de absorção de esteróis com agente (s) para o tratamento de doenças vasculares
ATE369851T1 (de) * 2001-01-26 2007-09-15 Schering Corp Kombinationen von gallensäuresequestriermitteln und hemmern der sterolabsorption zur behandlung von kardiovaskulären indikationen
US20020147184A1 (en) * 2001-01-26 2002-10-10 Schering Corporation Combinations of sterol absorption inhibitor(s) with blood modifier(s) for treating vascular conditions
BRPI0206641B8 (pt) * 2001-01-26 2021-05-25 Merck Sharp & Dohme uso de um inibidor da absorção de esteróis
EP1353695A2 (en) * 2001-01-26 2003-10-22 Schering Corporation Combinations of nicotinic acid and derivatives thereof and sterol absorption inhibitor(s) and treatments for vascular indications
US7071181B2 (en) * 2001-01-26 2006-07-04 Schering Corporation Methods and therapeutic combinations for the treatment of diabetes using sterol absorption inhibitors
CZ301487B6 (cs) * 2001-02-24 2010-03-17 Boehringer Ingelheim Pharma Gmbh & Co. Kg Xanthinové deriváty, jejich výroba a použití jako lécivo
KR200249057Y1 (ko) * 2001-03-22 2001-10-19 김진환 뚜껑, 받침대에 합체된 하수역류. 악취방지 장치
CN100577175C (zh) * 2001-04-04 2010-01-06 奥索-麦克尼尔药品公司 包括葡萄糖重吸收抑制剂和ppar调节剂的联合疗法
US20060047000A1 (en) * 2001-04-24 2006-03-02 Aryx Therapeutics, Inc. Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
CA2445322C (en) * 2001-04-25 2011-06-14 Takeda Chemical Industries, Ltd. Use of the abc expression promoting agent pioglitazone for the treatment of arteriosclerosis obliterans
AU2002311057A1 (en) * 2001-04-26 2002-11-11 Leciva, A.S. Method for obtaining pioglitazone as an antidiabetic agent
CA2448634A1 (en) * 2001-05-29 2002-12-05 Kyoto Pharmaceutical Industries, Ltd. Novel heterocyclic compound and medicinal use thereof
NZ530313A (en) * 2001-05-29 2005-06-24 Kyoto Pharma Ind Heterocyclic derivatives and medicinal use thereof
US20040219208A1 (en) * 2001-08-03 2004-11-04 Ryu Kawamura Sustained-release medicines
US7053080B2 (en) * 2001-09-21 2006-05-30 Schering Corporation Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors
CA2460340C (en) * 2001-09-21 2011-02-15 Schering Corporation Methods and therapeutic combinations for the treatment of xanthoma using sterol absorption inhibitors
EP1427409B1 (en) * 2001-09-21 2008-10-15 Schering Corporation Methods for treating or preventing vascular inflammation using sterol absorption inhibitor(s)
US20030119808A1 (en) * 2001-09-21 2003-06-26 Schering Corporation Methods of treating or preventing cardiovascular conditions while preventing or minimizing muscular degeneration side effects
US7056906B2 (en) * 2001-09-21 2006-06-06 Schering Corporation Combinations of hormone replacement therapy composition(s) and sterol absorption inhibitor(s) and treatments for vascular conditions in post-menopausal women
WO2003026586A2 (en) * 2001-09-28 2003-04-03 Teva Pharmaceutical Industries Ltd. Pioglitazone hydrochloride
US20050101638A1 (en) * 2002-11-08 2005-05-12 Webb Randy L. Combination of organic compounds
CA2470075A1 (en) * 2001-12-20 2003-07-03 Teva Pharmaceutical Industries Ltd. Hydrogenation of precursors to thiazolidinedione antihyperglycemics
US20050187258A1 (en) * 2001-12-20 2005-08-25 Ben-Zion Dolitzky Hydrogenation of precursors to thiazolidinedione antihyperglycemics
ITRM20020016A1 (it) 2002-01-15 2003-07-15 Sigma Tau Ind Farmaceuti Derivati di acidi fenil(alchil)carbossilici e derivati fenilalchileterociclici dionici, loro uso come medicamenti ad attivita' ipoglicemizza
WO2003062427A1 (fr) * 2002-01-23 2003-07-31 Yamanouchi Pharmaceutical Co., Ltd. Methode de criblage de medicaments ameliorant la resistance a l'insuline
US7015345B2 (en) * 2002-02-21 2006-03-21 Asahi Kasei Pharma Corporation Propionic acid derivatives
KR100450700B1 (ko) * 2002-03-22 2004-10-01 주식회사종근당 티아졸리딘디온 유도체 화합물 및 이를 함유하는 약제학적조성물
US20050119314A1 (en) * 2002-04-05 2005-06-02 Sankyo Company, Limited Pharmaceutical composition comprising an ACAT inhibitor and an insulin resistance reducing agent
US8911781B2 (en) 2002-06-17 2014-12-16 Inventia Healthcare Private Limited Process of manufacture of novel drug delivery system: multilayer tablet composition of thiazolidinedione and biguanides
ATE372336T1 (de) 2002-07-16 2007-09-15 Cadila Healthcare Ltd Prozess zur herstellung von pioglitazon via verschiedene zwischenstufen
US8993773B2 (en) 2002-07-16 2015-03-31 Cadila Healthcare Limited Process to prepare pioglitazone via several novel intermediates
US7407955B2 (en) * 2002-08-21 2008-08-05 Boehringer Ingelheim Pharma Gmbh & Co., Kg 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
WO2004024059A2 (en) * 2002-09-12 2004-03-25 Themis Laboratories Private Limited, Improved process for preparation of thiazolidinedione derivatives
US7959946B2 (en) 2002-09-20 2011-06-14 Watson Pharmaceuticals, Inc. Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative
WO2004026241A2 (en) 2002-09-20 2004-04-01 Andrx Labs Llc Multistage formulation containing a biguanide and thiazolidindione derivatives
US7785627B2 (en) * 2002-09-20 2010-08-31 Watson Pharmaceuticals, Inc. Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative
US8084058B2 (en) 2002-09-20 2011-12-27 Watson Pharmaceuticals, Inc. Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative
MXPA05004810A (es) * 2002-11-06 2005-07-22 Schering Corp Inhibidores de la absorcion del colesterol para el tratamiento de la desmielinizacion.
MXPA05009502A (es) 2003-03-07 2005-10-18 Schering Corp Compuestos de azetidinona sustituidos, formulaciones y usos de los mismos para el tratamiento de hipercolesterolemia.
US7459442B2 (en) 2003-03-07 2008-12-02 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
ATE406364T1 (de) * 2003-03-07 2008-09-15 Schering Corp Substituierte azetidinon-derivate, deren pharmazeutische formulierungen und deren verwendung zur behandlung von hypercholesterolemia
DE602004018617D1 (de) 2003-03-07 2009-02-05 Schering Corp Substituierte azetidinon-derivate, deren pharmazeutische formulierungen und deren verwendung zur behandlung von hypercholesterolemia
CA2518465A1 (en) 2003-03-25 2004-10-14 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
WO2004108721A1 (en) * 2003-04-01 2004-12-16 Sun Pharmaceutical Industries Limited Process for the preparation of 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl] methyl]-2,4-thiazolidinedione
ES2219180B1 (es) * 2003-05-09 2006-03-01 Medichem, S.A. Compuesto intermedio util para la preparacion de pioglitazona.
US7230016B2 (en) * 2003-05-13 2007-06-12 Synthon Ip Inc. Pioglitazone salts, such as pioglitazone sulfate, and pharmaceutical compositions and processes using the same
SI1622899T1 (sl) * 2003-05-13 2007-10-31 Synthon Bv Pioglitazonsulfat, farmacevtski sestavki in njihova uporaba
US20050059708A1 (en) * 2003-05-13 2005-03-17 Karel Pospisilik Processes for making thiazolidinedione derivatives and compounds thereof
US20050004179A1 (en) * 2003-05-22 2005-01-06 Pedersen Ward A. Methods and materials for treating, detecting, and reducing the risk of developing Alzheimer's Disease
US7718377B2 (en) * 2003-05-29 2010-05-18 Kyoto Pharmaceutical Industries, Ltd. Insulin resistance curative and method of screening the same
BRPI0410840A (pt) 2003-05-30 2006-07-04 Ranbaxy Lab Ltd derivados substituìdos de pirrol, composição farmacêutica contendo os mesmos e processo para sua preparação
KR20060041309A (ko) 2003-08-13 2006-05-11 다케다 야쿠힌 고교 가부시키가이샤 ４-피리미돈 유도체 및 펩티딜 펩티다제 저해제로서의 그의용도
WO2005021542A2 (en) * 2003-08-28 2005-03-10 Ranbaxy Laboratories Limited Process for the preparation of pioglitazone
AU2003269479A1 (en) * 2003-09-03 2005-03-16 Biocon Limited Phosphoric acid salt of 5-((4-(2-(5-ethyl-2-pyridinyl) ethoxy) phenyl) methyl)-2, 4-thiazolidinedione
WO2005026148A1 (en) 2003-09-08 2005-03-24 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
AU2003266526A1 (en) * 2003-09-17 2005-04-11 Kaname Kawasugi Medicinal composition
WO2005046797A2 (en) * 2003-11-05 2005-05-26 Schering Corporation Combinations of lipid modulating agents and substituted azetidinones and treatments for vascular conditions
US7501426B2 (en) * 2004-02-18 2009-03-10 Boehringer Ingelheim International Gmbh 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
EP1716144A2 (en) * 2004-02-20 2006-11-02 Synthon B.V. Processes for making pioglitazone and compounds of the processes
CN102134231B (zh) * 2004-03-15 2020-08-04 武田药品工业株式会社 二肽基肽酶抑制剂
CN1972715A (zh) * 2004-03-29 2007-05-30 三共株式会社 含有胰岛素抵抗改善剂的糖尿病治疗剂
US7161756B2 (en) * 2004-05-10 2007-01-09 Tandberg Data Storage Asa Method and system for communication between a tape drive and an external device
US20060025478A1 (en) * 2004-07-27 2006-02-02 Keisuke Inoue Medicine for prevention or treatment of diabetes
TW200608967A (en) * 2004-07-29 2006-03-16 Sankyo Co Pharmaceutical compositions containing with diabetic agent
EP1782832A4 (en) * 2004-08-26 2009-08-26 Takeda Pharmaceutical MEANS FOR THE TREATMENT OF DIABETES
WO2006035459A1 (en) * 2004-09-28 2006-04-06 Morepen Laboratories Limited An improved process for the production of derivatives of thiozolidinediones and their precursors
US20060089387A1 (en) * 2004-10-26 2006-04-27 Le Huang Stabilized pharmaceutical composition comprising antidiabetic agent
DE102004054054A1 (de) * 2004-11-05 2006-05-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine
US7833513B2 (en) 2004-12-03 2010-11-16 Rhode Island Hospital Treatment of Alzheimer's Disease
US7872124B2 (en) 2004-12-21 2011-01-18 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
JP5091106B2 (ja) * 2005-03-08 2012-12-05 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 真性糖尿病の治療のためのロフルミラスト
US20070269486A1 (en) * 2005-03-14 2007-11-22 Conor Medsystems, Llc. Methods and Devices for Reducing Tissue Damage After Ischemic Injury
JP2008533122A (ja) * 2005-03-18 2008-08-21 オーキッド ケミカルズ アンド ファーマシューティカルズ リミテッド 新規なチロシン誘導体
WO2006117654A1 (en) * 2005-05-03 2006-11-09 Ranbaxy Laboratories Limited Processes for the preparation of pioglitazone or salts thereof
EP1905450A1 (en) * 2005-07-12 2008-04-02 Daiichi Sankyo Company, Limited Pharmaceutical composition containing ppar gamma agonist
US20090203744A1 (en) * 2005-07-29 2009-08-13 Pande Y Surendrakumar Satyanarayan Novel pyridine derivatives
DE102005035891A1 (de) * 2005-07-30 2007-02-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
ATE532518T1 (de) * 2005-09-14 2011-11-15 Takeda Pharmaceutical Dipeptidyl-peptidase-hemmer zur behandlung von diabetes
CA2622642C (en) 2005-09-16 2013-12-31 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
TW200738266A (en) * 2005-09-29 2007-10-16 Sankyo Co Pharmaceutical agent containing insulin resistance improving agent
BRPI0618379A2 (pt) 2005-11-08 2011-08-30 Ranbaxy Lab Ltd processo para preparação do hemi-sal de cálcio do ácido (3r,5r) -7-[2-(4-fluorofenil)-5-isopropil-3-fenil-4-[(4-hidroxime tilfenilamino) carbonil]-pirrol-1-il] -3, 5-diidroxi heptanóico
TW200730173A (en) * 2005-12-16 2007-08-16 Sankyo Co Pharmaceutical composition enhancing production of adiponectin
CA2646149A1 (en) * 2006-03-16 2007-09-27 Metabolic Solutions Development Company Thiazolidinedione analogues for the treatment of hypertension and for lowering lipids
EP2001470A2 (en) * 2006-03-16 2008-12-17 Metabolic Solutions Development Company Combination therapies of thiazolidinedione analogues
RU2445957C2 (ru) 2006-03-16 2012-03-27 Метаболик Солюшнз Девелопмент Компани Аналоги тиазолидиндиона
EP1852108A1 (en) * 2006-05-04 2007-11-07 Boehringer Ingelheim Pharma GmbH & Co.KG DPP IV inhibitor formulations
PE20110235A1 (es) * 2006-05-04 2011-04-14 Boehringer Ingelheim Int Combinaciones farmaceuticas que comprenden linagliptina y metmorfina
NZ600394A (en) * 2006-05-04 2014-04-30 Boehringer Ingelheim Int Polymorphs of a dpp-iv enzyme inhibitor
US20080096900A1 (en) 2006-06-26 2008-04-24 Amgen Inc. Methods for treating atherosclerosis
KR100791399B1 (ko) 2006-09-06 2008-01-07 동우신테크 주식회사 염산 피오글리타존의 제조방법
EP2063890A1 (en) 2006-09-07 2009-06-03 Nycomed GmbH Combination treatment for diabetes mellitus
US8324383B2 (en) 2006-09-13 2012-12-04 Takeda Pharmaceutical Company Limited Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile
US20080182880A1 (en) * 2006-09-28 2008-07-31 Mailatur Sivaraman Mohan Pioglitazone composition
TW200838536A (en) 2006-11-29 2008-10-01 Takeda Pharmaceutical Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
JP2010513276A (ja) * 2006-12-13 2010-04-30 ギリード・サイエンシズ・インコーポレーテッド 肺炎症および気管支収縮の治療のための抗炎症シグナル伝達モジュレーター（ＡＩＳＴＭ）およびβ−アゴニストの相互プロドラッグとしてのモノホスフェート
WO2008075380A2 (en) * 2006-12-21 2008-06-26 Ind-Swift Laboratories Limited Process for the preparation of thiazolidine derivatives
EP2016076A2 (en) * 2007-01-22 2009-01-21 Teva Pharmaceutical Industries Ltd. Polymorphic forms of rosiglitazone hydrobromide and processes for preparation thereof
MX2009008100A (es) * 2007-02-01 2009-08-07 Takeda Pharmaceutical Preparacion solida que comprende alogliptina y pioglitazona.
CA2677661A1 (en) 2007-02-07 2008-08-14 Kyowa Hakko Kirin Co., Ltd. Tricyclic compounds
WO2008105326A1 (ja) * 2007-02-28 2008-09-04 Ohara Chemical Industries, Ltd. ２－イミノ－４－チアゾリジノン誘導体及び２，４－チアゾリジンジオン誘導体の製造方法
TW200901959A (en) 2007-03-09 2009-01-16 Indigene Pharmaceuticals Inc Combination of metformin R-(+) lipoate and antihyperlipidemic agents for the treatment of diabetic hyperglycemia and diabetic complications
US8093236B2 (en) * 2007-03-13 2012-01-10 Takeda Pharmaceuticals Company Limited Weekly administration of dipeptidyl peptidase inhibitors
WO2008121563A2 (en) * 2007-03-30 2008-10-09 Ambrx, Inc. Modified fgf-21 polypeptides and their uses
US20080249156A1 (en) * 2007-04-09 2008-10-09 Palepu Nageswara R Combinations of statins and anti-obesity agent and glitazones
US20160331729A9 (en) * 2007-04-11 2016-11-17 Omeros Corporation Compositions and methods for prophylaxis and treatment of addictions
RU2492858C2 (ru) * 2007-04-11 2013-09-20 Омерос Корпорейшн Композиции и способы профилактики и лечения зависимостей
US11241420B2 (en) 2007-04-11 2022-02-08 Omeros Corporation Compositions and methods for prophylaxis and treatment of addictions
EA201401193A1 (ru) 2007-06-04 2015-08-31 Бен-Гурион Юниверсити Оф Дзе Негев Рисерч Энд Дивелопмент Оторити Триарильные соединения и композиции, их содержащие
EP2527360B1 (en) 2007-06-04 2015-10-28 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
US8969514B2 (en) 2007-06-04 2015-03-03 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
NZ597885A (en) 2007-07-26 2013-08-30 Amgen Inc Modified lecithin-cholesterol acyltransferase enzymes
US20110112069A1 (en) * 2007-08-17 2011-05-12 Boehringer Ingelheim International Gmbh Purin derivatives for use in the treatment of fab-related diseases
BRPI0817096B8 (pt) 2007-09-14 2021-05-25 Cirius Therapeutics Inc análogo de tiazolidinodiona e composição farmacêutica que o compreende
US8304441B2 (en) 2007-09-14 2012-11-06 Metabolic Solutions Development Company, Llc Thiazolidinedione analogues for the treatment of metabolic diseases
US7960376B2 (en) * 2007-09-14 2011-06-14 Cara Therapeutics, Inc. Benzo-fused heterocycles
US8722710B2 (en) 2007-09-26 2014-05-13 Deuterx, Llc Deuterium-enriched pioglitazone
US20090118514A1 (en) * 2007-11-06 2009-05-07 Raghupathi Reddy Anumula Processes for preparing pioglitazone and its pharmaceutically acceptable salts
JP5334422B2 (ja) * 2008-02-13 2013-11-06 株式会社トクヤマ ５−｛４−［２−（５−エチル−２−ピリジル）エトキシ］ベンジル｝−２−イミノ−４−チアゾリジノンの製造方法
JP5197063B2 (ja) * 2008-02-21 2013-05-15 株式会社トクヤマ ２−ブロモ−３−｛４−［２−（５−エチル−２−ピリジル）エトキシ］フェニル｝プロピオン酸メチルの製造方法
PE20091730A1 (es) 2008-04-03 2009-12-10 Boehringer Ingelheim Int Formulaciones que comprenden un inhibidor de dpp4
JP2011518877A (ja) * 2008-04-28 2011-06-30 エレジーレ ソシエタ ペル アチオニ ４−［２−（５−エチル−２−ピリジル）エトキシ］ニトロベンゼン及びピオグリタゾンの調製方法
PE20100156A1 (es) * 2008-06-03 2010-02-23 Boehringer Ingelheim Int Tratamiento de nafld
ES2627848T3 (es) 2008-06-04 2017-07-31 Synergy Pharmaceuticals Inc. Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos
WO2010009319A2 (en) 2008-07-16 2010-01-21 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
US8486980B2 (en) 2008-08-06 2013-07-16 Kyowa Hakko Kirin Co., Ltd. Tricyclic compound
BRPI0916997A2 (pt) 2008-08-06 2020-12-15 Boehringer Ingelheim International Gmbh Inibidor de dpp-4 e seu uso
UY32030A (es) 2008-08-06 2010-03-26 Boehringer Ingelheim Int "tratamiento para diabetes en pacientes inapropiados para terapia con metformina"
US8815508B2 (en) 2008-08-12 2014-08-26 Zinfandel Pharmaceuticals, Inc. Method of identifying disease risk factors
US8846315B2 (en) 2008-08-12 2014-09-30 Zinfandel Pharmaceuticals, Inc. Disease risk factors and methods of use
NZ604091A (en) * 2008-08-15 2014-08-29 Boehringer Ingelheim Int Purin derivatives for use in the treatment of fab-related diseases
CN102112444A (zh) * 2008-09-02 2011-06-29 株式会社德山 脱溴化氢化抑制剂
BRPI0919288A2 (pt) 2008-09-10 2015-12-15 Boehring Ingelheim Internat Gmbh teriapia de combinação para tratamento de diabetes e condições relacionadas.
US20200155558A1 (en) 2018-11-20 2020-05-21 Boehringer Ingelheim International Gmbh Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug
JP5473303B2 (ja) * 2008-12-01 2014-04-16 株式会社トクヤマ ２−ブロモ−３−｛４−［２−（５−エチル−２−ピリジル）エトキシ］フェニル｝プロピオン酸メチルの製造方法
US20100144140A1 (en) * 2008-12-10 2010-06-10 Novellus Systems, Inc. Methods for depositing tungsten films having low resistivity for gapfill applications
EP2382216A1 (en) 2008-12-23 2011-11-02 Boehringer Ingelheim International GmbH Salt forms of organic compound
TW201036975A (en) 2009-01-07 2010-10-16 Boehringer Ingelheim Int Treatment for diabetes in patients with inadequate glycemic control despite metformin therapy
CN102227408A (zh) * 2009-01-20 2011-10-26 株式会社德山 抑制2-溴-3-{4-[2-(5-乙基-2-吡啶基)乙氧基]苯基}丙酸甲酯的脱溴化氢化的方法
JP2010208957A (ja) * 2009-03-06 2010-09-24 Tokuyama Corp 結晶構造を有する５−｛４−［２−（５−エチル−２−ピリジル）エトキシ］ベンジル｝−２−イミノ−４−チアゾリジノン及びその製造方法
JP6163289B2 (ja) 2009-03-11 2017-07-12 オメロス コーポレーション 嗜癖の予防および治療のための組成物および方法
EP2445343B1 (en) 2009-06-25 2021-08-04 Alkermes Pharma Ireland Limited Prodrugs of nh-acidic compounds
JP5733841B2 (ja) 2009-06-25 2015-06-10 アルカーメス ファーマ アイルランド リミテッド 神経学的および精神的障害の治療のための複素環式化合物
US20110065756A1 (en) * 2009-09-17 2011-03-17 De Taeye Bart M Methods and compositions for treatment of obesity-related diseases
KR101701943B1 (ko) 2009-11-13 2017-02-02 도레이 카부시키가이샤 당뇨병의 치료 또는 예방약
KR20230021159A (ko) 2009-11-27 2023-02-13 베링거 인겔하임 인터내셔날 게엠베하 리나글립틴과 같은 ｄｐｐ－ｉｖ 억제제를 사용한 유전자형 검사된 당뇨병 환자의 치료
AU2010340055B2 (en) * 2009-12-15 2014-07-24 Cirius Therapeutics, Inc. PPAR-sparing thiazolidinedione salts for the treatment of metabolic diseases
US10429384B2 (en) 2010-01-22 2019-10-01 Dana-Farber Cancer Institute, Inc. Compositions, kits, and methods for identification, assessment, prevention, and therapy of metabolic disorders
US20140088027A1 (en) 2010-03-30 2014-03-27 Boehringer Ingelheim International Gmbh Pharmaceutical composition comprising an sglt2 inhibitor and a ppar- gamma agonist and uses thereof
CN102946875A (zh) 2010-05-05 2013-02-27 贝林格尔.英格海姆国际有限公司 组合疗法
WO2011161161A1 (en) 2010-06-24 2011-12-29 Boehringer Ingelheim International Gmbh Diabetes therapy
WO2012028934A1 (en) 2010-09-01 2012-03-08 Lupin Limited Pharmaceutical composition comprising metformin and pioglitazone
US9616097B2 (en) 2010-09-15 2017-04-11 Synergy Pharmaceuticals, Inc. Formulations of guanylate cyclase C agonists and methods of use
US9034883B2 (en) 2010-11-15 2015-05-19 Boehringer Ingelheim International Gmbh Vasoprotective and cardioprotective antidiabetic therapy
CN107362165A (zh) 2011-01-10 2017-11-21 金帆德尔制药股份有限公司 用于治疗阿尔茨海默病的方法和药物产品
WO2012153312A1 (en) 2011-05-11 2012-11-15 Ranbaxy Laboratories Limited Process for the purification of pioglitazone
NZ618698A (en) 2011-07-15 2015-08-28 Boehringer Ingelheim Int Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions
WO2013018899A1 (ja) 2011-08-03 2013-02-07 協和発酵キリン株式会社 ジベンゾオキセピン誘導体
WO2013068486A1 (en) 2011-11-08 2013-05-16 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the diagnosis and treatment of male infertility
WO2013086443A1 (en) 2011-12-08 2013-06-13 Amgen Inc. Agonistic human lcat antigen binding proteins and their use in therapy
AU2012351747B2 (en) 2011-12-15 2016-05-12 Alkermes Pharma Ireland Limited Prodrugs of secondary amine compounds
US20130158077A1 (en) 2011-12-19 2013-06-20 Ares Trading S.A. Pharmaceutical compositions
US9504679B2 (en) 2011-12-19 2016-11-29 Bjoern Colin Kahrs Pharmaceutical compositions comprising glitazones and Nrf2 activators
US9555001B2 (en) 2012-03-07 2017-01-31 Boehringer Ingelheim International Gmbh Pharmaceutical composition and uses thereof
EP2638898A1 (en) 2012-03-16 2013-09-18 Sanovel Ilac Sanayi ve Ticaret A.S. Metformin and Pioglitazone Formulation with Different Release Profiles
US20130303462A1 (en) 2012-05-14 2013-11-14 Boehringer Ingelheim International Gmbh Use of a dpp-4 inhibitor in podocytes related disorders and/or nephrotic syndrome
WO2013174767A1 (en) 2012-05-24 2013-11-28 Boehringer Ingelheim International Gmbh A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference
CA2890086C (en) 2012-11-05 2022-05-31 Commissariat A L'energie Atomique Et Aux Energies Alternatives (Cea) Combination of an anti-cancer agent such as a tyrosinekinase inhibitor and a stat5 antagonist preferably a thiazolid nedione, for eliminating hematologic cancer stem cells in vivo and for preventing hematologic cancer relapse
JP6800013B2 (ja) 2013-03-14 2020-12-16 ポクセル・ソシエテ・アノニムＰｏｘｅｌ ＳＡ 重水素化２，４−チアゾリジンジオン及び治療方法
JP2016514670A (ja) 2013-03-15 2016-05-23 シナジー ファーマシューティカルズ インコーポレイテッド 他の薬物と組み合わせたグアニル酸シクラーゼ受容体アゴニスト
JP2016514671A (ja) 2013-03-15 2016-05-23 シナジー ファーマシューティカルズ インコーポレイテッド グアニル酸シクラーゼのアゴニストおよびその使用
US20140275138A1 (en) * 2013-03-15 2014-09-18 Cba Pharma, Inc. Method and products for treating diabetes
BR112015030326A2 (pt) 2013-06-05 2017-08-29 Synergy Pharmaceuticals Inc Agonistas ultrapuros de guanilato ciclase c, método de fabricar e usar os mesmos
WO2015042495A2 (en) * 2013-09-22 2015-03-26 Jiva Pharma, Inc. Metformin salts to treat type2 diabetes
CA2926685A1 (en) 2013-10-09 2015-04-16 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for downregulation of pro-inflammatory cytokines
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
US10188639B2 (en) 2014-01-15 2019-01-29 Deuterx, Llc Methods of treating neurological, metabolic, and other disorders using enantiopure deuterium-enriched pioglitazone
JP6615109B2 (ja) 2014-02-28 2019-12-04 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｄｐｐ−４阻害薬の医学的使用
KR101606547B1 (ko) * 2014-06-02 2016-03-28 김동연 공항 탑승객 위치조회시스템
TW202124419A (zh) 2014-10-24 2021-07-01 美商必治妥美雅史谷比公司 經修飾之fgf-21多肽及其用途
WO2016071727A1 (en) 2014-11-04 2016-05-12 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the prevention and the treatment of rapidly progressive glomerulonephritis
MA39929A (fr) 2014-11-27 2016-06-01 Arven Ilac Sanayi Ve Ticaret As Comprimé multicouche comprenant de la metformine et du pioglitazone
CN109414506B (zh) 2016-06-08 2022-06-03 投资支持有限公司 用于治疗癌症的药物组合
JP2019517542A (ja) 2016-06-10 2019-06-24 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング リナグリプチンおよびメトホルミンの組合せ
AU2017313296A1 (en) 2016-08-17 2019-02-14 Support-Venture Gmbh Method of preventing or treating hearing loss
TR201620309A2 (tr) 2016-12-30 2018-07-23 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Metformi̇n hi̇droklori̇t ve pi̇ogli̇tazon hi̇droklori̇ti̇n farmasöti̇k bi̇leşi̇mleri̇
MA49040A (fr) 2017-04-04 2020-02-12 Strekin Ag Procédés de prévention ou de traitement de maladies ophtalmiques
WO2019154893A1 (en) 2018-02-08 2019-08-15 Strekin Ag Oral extended release pharmaceutical compositions for preventing or treating hearing loss
WO2019154895A1 (en) 2018-02-08 2019-08-15 Strekin Ag Gel formulation for preventing or treating hearing loss
JP7384812B2 (ja) 2018-03-05 2023-11-21 アルカームス ファーマ アイルランド リミテッド アリピプラゾール投与戦略
US20210267983A1 (en) 2018-07-13 2021-09-02 Kinarus Ag Combinations of ppar agonists and p38 kinase inhibitors for preventing or treating fibrotic diseases
CN111875598B (zh) * 2020-05-23 2023-10-10 白银京宇新药业有限公司 一种吡格亚胺的制备方法
US11319313B2 (en) 2020-06-30 2022-05-03 Poxel Sa Crystalline forms of deuterium-enriched pioglitazone
US11767317B1 (en) 2020-06-30 2023-09-26 Poxel Sa Methods of synthesizing enantiopure deuterium-enriched pioglitazone
WO2022034031A1 (en) 2020-08-11 2022-02-17 Kinarus Ag Methods of preventing or treating covid-19 and related viral diseases or disorders
CN115925796A (zh) 2020-09-30 2023-04-07 映恩生物制药（苏州）有限公司 一种抗肿瘤化合物及其制备方法和应用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5522636A (en) * 1978-08-04 1980-02-18 Takeda Chem Ind Ltd Thiazoliding derivative
US4582839A (en) * 1984-03-21 1986-04-15 Takeda Chemical Industries, Ltd. 2,4-thiazolidinediones
CN1003445B (zh) * 1984-10-03 1989-03-01 武田药品工业株式会社 噻唑烷二酮衍生物，其制备方法和用途

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4812570A (en) * 1986-07-24 1989-03-14 Takeda Chemical Industries, Ltd. Method for producing thiazolidinedione derivatives
US4898947A (en) * 1986-07-24 1990-02-06 Takeda Chemical Industries, Ltd. Pyridine and thiazolidinedione derivatives
USRE36575E (en) * 1986-07-24 2000-02-15 Takeda Chemical Industries, Ltd. Pyridine and thiazolidinedione derivatives
CN101222912B (zh) * 2005-03-30 2012-10-03 华生制药公司 包含双胍和噻唑烷二酮衍生物的药物新剂型
CN102149669A (zh) * 2008-10-10 2011-08-10 株式会社德山 羰氧基化合物的制备方法

Also Published As

Publication number Publication date
SG105691G (en) 1992-02-14
FI81098C (fi) 1990-09-10
ES8705886A1 (es) 1987-05-16
FI81098B (fi) 1990-05-31
GR860124B (en) 1986-05-19
ZA86203B (en) 1987-09-30
FI860232A (fi) 1986-07-20
ES550986A0 (es) 1987-05-16
PT81859A (en) 1986-02-01
MY102016A (en) 1992-02-29
FI860232A0 (fi) 1986-01-17
EP0193256A1 (en) 1986-09-03
AU572719B2 (en) 1988-05-12
HK3692A (en) 1992-01-17
ATE41931T1 (de) 1989-04-15
NO860141L (no) 1986-07-21
JPS61267580A (ja) 1986-11-27
KR860005811A (ko) 1986-08-13
LU90719I2 (fr) 2001-03-26
DE10199018I1 (de) 2001-07-12
LV5779A4 (lv) 1996-12-20
LV5779B4 (lv) 1997-04-20
NO163857B (no) 1990-04-23
AR240698A1 (es) 1990-09-28
CS407991A3 (en) 1992-04-15
HUT41775A (en) 1987-05-28
KR920010046B1 (ko) 1992-11-13
IE860107L (en) 1986-07-19
BR1100325A (pt) 2000-06-27
CA1277323C (en) 1990-12-04
DE10199018I2 (de) 2006-02-02
NO163857C (no) 1990-08-01
CN1003934B (zh) 1989-04-19
NL300038I2 (nl) 2001-05-01
DK21986A (da) 1986-07-20
DK21986D0 (da) 1986-01-17
DK171614B1 (da) 1997-02-24
MX9202933A (es) 1992-06-30
US4687777A (en) 1987-08-18
JPH0566956B2 (zh) 1993-09-22
PT81859B (pt) 1988-05-27
HU196795B (en) 1989-01-30
EP0193256B1 (en) 1989-04-05
DE3662689D1 (en) 1989-05-11
AU5246786A (en) 1986-07-24
IE58928B1 (en) 1993-12-01

Similar Documents

Publication Publication Date Title
CN86100411A (zh) 生产噻唑烷二酮的方法
CN1051312C (zh) 一种噻唑烷衍生物及其制药应用
CN1026322C (zh) 苯并哑唑衍生物的制备方法
KR920002131B1 (ko) 타아졸리딘디온 유도체의 제조방법
CN1065863C (zh) N-取代二氧代噻唑烷基苯甲酰胺衍生物及其制备方法
EP0542816A1 (en) Oxazolidine dione derivatives
CN105358145A (zh) 协同组合物
CN1845917A (zh) 3－[(2－{[4－(已氧基羰基氨基－亚氨基－甲基)－苯氨基]－甲基}－1－甲基－1 h－苯并咪唑－5－羰基)－吡啶－2－基－氨基]－丙酸乙酯－甲磺酸酯及其作为药物的用途
EP0356214A2 (en) Thiazolidine dione derivatives
CN1167702C (zh) 5-[4-[2-n-甲基-n-(2-吡啶基)氨基]乙氧基]苄基]噻唑烷-2,4-二酮马来酸盐的多晶型物
CN1152304A (zh) 经取代的苄脒，其制备及作为药物化合物的用途
CN1019911C (zh) 新的苯并嗪衍生物的制备方法
WO2021196949A1 (zh) 一种glp-1受体激动剂的晶型a及其制备方法
FR2580642A1 (fr) 5-pyrimidinecarboxamides et traitement de la leucemie et des tumeurs en les utilisant
FR2480286A1 (fr) Nouveaux derives de theophyllinylmethyldioxolane, leurs procedes de preparation et leur application en therapeutique
JPS63174926A (ja) 家禽用抗コクシジウム剤
JPS61122212A (ja) 新規血糖降下剤
CN85101435A (zh) 新型化合物n，n′-甲撑-双(2氨基-5巯基-1，3，4噻二唑)制备方法及含此化合物的防治植物细菌性，病害杀菌剂
CN1594307A (zh) 野葛花中尼泊尔鸢尾异黄酮的提取分离及其磺化物制备方法和药物用途
CN1056369C (zh) 哒嗪酮衍生物或其盐和制备方法
EP0101380A2 (fr) Nicotinamide 1-oxyde N-substitué, ses sels, procédé pour leur préparation et compositions pharmaceutiques en contenant
CN1112113A (zh) 新的三唑化合物及其制备方法和用途
CN1027893C (zh) 制备新的1，2-二硫杂环戊烯-3-硫酮-s-氧化物的方法
CA1210392A (fr) Procede pour la preparation d'amides n-substitues, et les amides ainsi obtenus
CN106279139A (zh) 可用作sglt2抑制剂的化合物及其制备方法和用途

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C13 Decision
GR02 Examined patent application
C14 Grant of patent or utility model
GR01 Patent grant
C17 Cessation of patent right
CX01 Expiry of patent term