CN1003934B - 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
CN1003934B
CN1003934B CN86100411.6A CN86100411A CN1003934B CN 1003934 B CN1003934 B CN 1003934B CN 86100411 A CN86100411 A CN 86100411A CN 1003934 B CN1003934 B CN 1003934B
Authority
CN
China
Prior art keywords
chemical compound
gram
ethyoxyl
pyridine radicals
reaction
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
Application number
CN86100411.6A
Other languages
English (en)
Other versions
CN86100411A (zh
Inventor
目黑宽司
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=CN1003934(B) "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

生产噻唑烷二酮的方法
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，在日本特开昭55-22636和特开昭55-64586以及“化学和药物公报”（Chemical ＆ Pharmaceutical Bulletion），第30卷，第3563页（1982），以及同一上述文献，第30卷，第3580页（1982）和第32卷，第2267页（1984）等文献中，提到了具有使血葡萄糖和血脂降低作用的各和噻唑烷二酮类。在“糖尿病”（Diabetes），第32卷，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_IMG5
（Ⅰ）
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_IMG6
（Ⅱ）
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）”），可由对式（Ⅱ）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：
Figure 86100411_IMG7
其中R代表氢或者低级烷基。
由R所代表的低级烷基，包括甲基、乙基、丙基、异丙基和丁基等类似的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（Ⅶ）。化合物（Ⅶ）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）、二甲基亚砜和四氢噻吩砜等之中进行。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（Ⅶ）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〈＆＆〉，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百分数，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）、（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HB，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，52.30%）。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。
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_IMG10
参 照 例 2
按照实施例1-b）制备下列化合物。
2-溴-3-｛4-〔2-（3-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，CDCl2）：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），6.7-7.36（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℃。
C14H16N2O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_IMG11
参 照 例 6
按照实施例1-d）制备表4中所列的化合物。
Figure 86100411_IMG13
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℃。
C16H18N2O3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 (8)

1、一种制备式（Ⅰ）的化合物或其药理上可接受盐的方法，
Figure 86100411_IMG2
　（Ⅰ）
其特征在于在醇类、二甲基亚砜、四氢噻吩砜等溶剂存在下以及20℃到180℃的反应条件下，将化合物（Ⅷ）与硫脲反应得到化合物（Ⅱ），
其中式（Ⅷ）为
Figure 86100411_IMG4
在无机酸的存在下，将式（Ⅱ）的化合物在有机溶剂中进行水解反应，并维持该反应在20℃到150℃的温度范围及0.5到20小时。
2、根据权利要求1所述的方法，其中所述的有机溶剂选自醇类、二甲基亚砜、二氧噻吩烷、二噁烷、四氢呋喃或二甲氧基乙烷。
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 CN86100411A (zh) 1986-07-16
CN1003934B true 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) DK21986A (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 (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Families Citing this family (270)

* 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
US4812570A (en) * 1986-07-24 1989-03-14 Takeda Chemical Industries, Ltd. Method for producing thiazolidinedione derivatives
FI91869C (fi) * 1987-03-18 1994-08-25 Tanabe Seiyaku Co Menetelmä antidiabeettisena aineena käytettävien bensoksatsolijohdannaisten valmistamiseksi
WO1988009661A1 (en) * 1987-06-10 1988-12-15 Pfizer Inc. Oxazolidin-2-one derivatives as hypoglycemic agents
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
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
US4791125A (en) * 1987-12-02 1988-12-13 Pfizer Inc. Thiazolidinediones as hypoglycemic and anti-atherosclerosis agents
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
US5356913A (en) * 1990-02-09 1994-10-18 The Upjohn Company Use of insulin sensitizing agents to treat hypertension
ATE93138T1 (de) * 1990-02-09 1993-09-15 Upjohn Co Verwendung insulin-sensiblisierender wirkstoffe zur behandlung von hypertonie.
ATE205206T1 (de) * 1990-04-27 2001-09-15 Sankyo Co Benzylidenthiazolidinderivate, ihre herstellung und ihre anwendung als lipidperoxid-inhibitoren
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
ATE202352T1 (de) * 1991-04-11 2001-07-15 Upjohn Co Thiazolidindionderivate, herstellung und anwendung
US5183823A (en) * 1991-04-11 1993-02-02 Takeda Chemical Industries, Ltd. Pyridine n-oxide compounds which are useful as hypoglycemic and hypolipidemic agents
US5441971A (en) * 1991-04-11 1995-08-15 The Upjohn Company Thiazolidinedione derivatives, production and use thereof
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
ZA936492B (en) * 1992-09-10 1995-03-02 Lilly Co Eli 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
US5478852C1 (en) * 1993-09-15 2001-03-13 Sankyo Co Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of impaired glucose tolerance in order to prevent or delay the onset of 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
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
CN1103590C (zh) * 1993-09-15 2003-03-26 三共株式会社 使用噻唑烷二酮防止或延缓非胰岛素依赖性糖尿病(niddm)的发作
CZ284592B6 (cs) * 1994-03-08 1999-01-13 American Home Products Corporation Thiazolidindionové deriváty a farmaceutický prostředek s jejich obsahem
US6251928B1 (en) * 1994-03-16 2001-06-26 Eli Lilly And Company Treatment of alzheimer's disease employing inhibitors of cathepsin D
AU712802B2 (en) * 1994-10-20 1999-11-18 Nippon Chemiphar Co. Ltd. Quinoline derivatives
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
TW474809B (en) * 1995-07-03 2002-02-01 Sankyo Co A pharmaceutical composition for arteriosclerosis or xanthoma consisting of HMG-CoA reductase inhibitors and insulin sensitizers
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
JP2000511883A (ja) * 1996-04-19 2000-09-12 ノボ ノルディスク アクティーゼルスカブ ホスホチロシン認識ユニットを有する分子のモジュレーター
US5958957A (en) * 1996-04-19 1999-09-28 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
EP0974348B1 (en) * 1996-11-08 2008-07-02 Nippon Chemiphar Co., Ltd. Visceral fat lowering agent
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
JP4693247B2 (ja) 1999-04-28 2011-06-01 有限会社ケムフィズ 複素環カルボン酸誘導体
JP2001072592A (ja) 1999-07-01 2001-03-21 Kyowa Hakko Kogyo Co Ltd テロメラーゼ阻害剤
CA2341253A1 (en) * 1999-07-01 2001-01-11 Allison C. Chin Telomerase inhibitors and methods of their use
US7390824B1 (en) * 1999-09-07 2008-06-24 Bristol-Myers Squibb Company Method for treating diabetes employing an aP2 inhibitor and combination
CO5200844A1 (es) 1999-09-17 2002-09-27 Novartis Ag Una combinacion que comprende nateglinida y cuando por menos otro compuesto antidiabetico usada para el tratamiento de desordenes metabolicos, especialmente diabetes, o de una enfermedad o condicion asociada con dibetes
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
ES2156574B1 (es) 1999-11-18 2002-02-01 Vita Invest Sa Nuevos derivados de tiazolidindiona como agentes antidiabeticos
KR100716525B1 (ko) 1999-12-03 2007-05-10 교토 야쿠힝 고교 가부시키가이샤 신규한 헤테로시클릭 화합물과 이의 염 및 이들의 의약 용도
DE60132723T2 (de) 2000-01-21 2009-01-29 Novartis Pharma Ag 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
US6784199B2 (en) 2000-09-21 2004-08-31 Aryx Therapeutics Isoxazolidine compounds useful in the treatment of diabetes, hyperlipidemia, and atherosclerosis in mammals
EP1277745A4 (en) * 2000-04-25 2004-09-15 Kyorin Seiyaku Kk NEW STABLE CRYSTALS OF THIAZOLIDINDION DERIVATIVES AND METHOD FOR THE PRODUCTION THEREOF
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
DE60123665T2 (de) * 2000-12-26 2007-08-16 Sankyo Co., Ltd. Medizinische zusammensetzungen mit diuretischem und die insulinresistenz verbesserndem mittel
CA2434033A1 (en) * 2001-01-26 2002-08-01 Schering Corporation Combinations of bile acid sequestrant(s) and sterol absorption inhibitor(s) and treatments for vascular indications
AR035533A1 (es) * 2001-01-26 2004-06-02 Schering Corp Uso de por lo menos un inhibidor de la absorcion de los esteroles o sus sales, solvatos, prodrogas farmaceuticamente aceptables o mezclas de los mismos para la preparacion de un medicamento para el tratamiento de la sitosterolemia, composiciones farmaceuticas, el uso de dichas composiciones para la
US20020151536A1 (en) * 2001-01-26 2002-10-17 Schering Corporation Combinations of peroxisome proliferator-activated receptor (PPAR) activator(s) 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
CA2434488A1 (en) * 2001-01-26 2002-08-01 Harry R. Davis Combinations of nicotinic acid and derivatives thereof and sterol absorption inhibitor(s) and treatments for vascular indications
EP1385548B1 (en) * 2001-01-26 2007-05-23 Schering Corporation Combinations of sterol absorption inhibitor(s) with cardiovascular agent(s) for the treatment of vascular conditions
SK9502003A3 (en) * 2001-01-26 2003-12-02 Schering Corp Combinations of sterol absorption inhibitor(s) with blood modifier(s) for treating vascular conditions
DK1953162T3 (da) * 2001-02-24 2012-09-10 Boehringer Ingelheim Pharma Xanthinderivater, deres fremstilling og deres anvendelse som lægemiddel.
KR200249057Y1 (ko) * 2001-03-22 2001-10-19 김진환 뚜껑, 받침대에 합체된 하수역류. 악취방지 장치
EP1381361B1 (en) * 2001-04-04 2009-02-25 Ortho-McNeil-Janssen Pharmaceuticals, Inc. Combination therapy comprising glucose reabsorption inhibitors and ppar modulators
US20060047000A1 (en) * 2001-04-24 2006-03-02 Aryx Therapeutics, Inc. Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
US20040077689A1 (en) * 2001-04-25 2004-04-22 Yasuo Sugiyama Abc expression promoters
US7009057B2 (en) 2001-04-26 2006-03-07 Zentiva 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
US6872732B2 (en) * 2001-05-29 2005-03-29 Kyoto Pharmaceutical Industries, Ltd. Heterocyclic derivatives and medicinal use thereof
CA2456034A1 (en) * 2001-08-03 2003-02-20 Takeda Chemical Industries, Ltd. Sustained-release medicines
DK1427409T3 (da) * 2001-09-21 2009-01-12 Schering Corp Fremgangsmåde til behandling eller forhindring af vaskulær inflammation under brug af en eller flere sterolabssorptionsinhibitorer
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
US7053080B2 (en) * 2001-09-21 2006-05-30 Schering Corporation Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors
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
JP2005504091A (ja) * 2001-09-21 2005-02-10 シェーリング　コーポレイション ステロール吸収阻害剤としてアゼチジノンを用いる黄色腫の処置
US7135485B2 (en) * 2001-09-28 2006-11-14 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
WO2003105809A1 (en) 2002-06-17 2003-12-24 Themis Laboratories Private Limited Multilayer tablets containing thiazolidinedione and biguanides and methods for producing them
US7465801B2 (en) 2002-07-16 2008-12-16 Cadila Healthcare Limited Process to prepare pioglitazone via several novel intermediates
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
AU2003260813A1 (en) * 2002-09-12 2004-04-30 Themis Laboratories Private Limited Improved process for preparation of thiazolidinedione derivatives
KR101363679B1 (ko) 2002-09-20 2014-02-14 안드렉스 랩스 엘엘씨 약제학적 정제
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
US9060941B2 (en) * 2002-09-20 2015-06-23 Actavis, Inc. Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative
US7959946B2 (en) 2002-09-20 2011-06-14 Watson Pharmaceuticals, Inc. Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative
MXPA05004811A (es) * 2002-11-06 2005-07-22 Schering Corp Inhibidores de absorcion de colesterol para el tratamiento de trastornos autoinmunes.
CN1756755A (zh) 2003-03-07 2006-04-05 先灵公司 取代的2－吖丁啶酮化合物、其制剂及其治疗高胆甾醇血症的用途
US7459442B2 (en) 2003-03-07 2008-12-02 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
MXPA05009503A (es) 2003-03-07 2005-10-18 Schering Corp Compuestos de azetidinona sustituidos, formulaciones y usos de los mismos para el tratamiento de hipercolesterolemia.
US7208486B2 (en) 2003-03-07 2007-04-24 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7687625B2 (en) 2003-03-25 2010-03-30 Takeda Pharmaceutical Company Limited 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.
EP1640374A1 (en) * 2003-05-13 2006-03-29 Synthon B.V. Pioglitazone salts, such as pioglitazone sulfate, and pharmaceutical compositions and processes using the same
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
WO2004101560A1 (en) * 2003-05-13 2004-11-25 Synthon B.V. 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
US7923467B2 (en) 2003-05-30 2011-04-12 Ranbaxy Laboratories, Inc. Substituted pyrrole derivatives and their use as HMG-CO inhibitors
EP1506967B1 (en) 2003-08-13 2007-11-21 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
US20070078170A1 (en) * 2003-08-28 2007-04-05 Khanduri Chandra H 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
JP2007505121A (ja) 2003-09-08 2007-03-08 武田薬品工業株式会社 ジペプチジルぺプチダーゼ阻害剤
JP5140881B2 (ja) * 2003-09-17 2013-02-13 要 川杉 医薬組成物
CA2544309A1 (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
CN102134229B (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
CA2560928A1 (en) * 2004-03-29 2005-10-06 Sankyo Company Limited Therapeutic agent for diabetes containing insulin resistance improving agent
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
WO2006022428A1 (ja) * 2004-08-26 2006-03-02 Takeda Pharmaceutical Company Limited 糖尿病治療剤
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
EP1828192B1 (en) 2004-12-21 2014-12-03 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
CN102600144A (zh) * 2005-03-08 2012-07-25 奈科明有限责任公司 治疗糖尿病的罗氟司特
US20070269486A1 (en) * 2005-03-14 2007-11-22 Conor Medsystems, Llc. Methods and Devices for Reducing Tissue Damage After Ischemic Injury
KR20080025662A (ko) * 2005-03-18 2008-03-21 오키드 케미칼즈 앤드 파마수티컬즈 리미티드 신규 티로신 유도체
WO2006117654A1 (en) * 2005-05-03 2006-11-09 Ranbaxy Laboratories Limited Processes for the preparation of pioglitazone or salts thereof
JPWO2007007757A1 (ja) * 2005-07-12 2009-01-29 第一三共株式会社 ＰＰＡＲγアゴニストを含有する医薬組成物
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
EA015169B1 (ru) * 2005-09-14 2011-06-30 Такеда Фармасьютикал Компани Лимитед Применение ингибиторов дипептидилпептидазы
CN102675221A (zh) 2005-09-16 2012-09-19 武田药品工业株式会社 用于制备嘧啶二酮衍生物的方法中的中间体
TW200738266A (en) * 2005-09-29 2007-10-16 Sankyo Co Pharmaceutical agent containing insulin resistance improving agent
JP2009514851A (ja) 2005-11-08 2009-04-09 ランバクシー ラボラトリーズ リミテッド （３ｒ，５ｒ）−７−［２−（４−フルオロフェニル）−５−イソプロピル−３−フェニル−４−［（４−ヒドロキシメチルフェニルアミノ）カルボニル］−ピロール−１−イル］−３，５−ジヒドロキシ−ヘプタン酸ヘミカルシウム塩の製法
TW200730173A (en) * 2005-12-16 2007-08-16 Sankyo Co Pharmaceutical composition enhancing production of adiponectin
ES2397944T3 (es) * 2006-03-16 2013-03-12 Metabolic Solutions Development Company Llc Análogos de tiazolidindiona
JP5149271B2 (ja) * 2006-03-16 2013-02-20 メタボリック ソリューションズ ディベロップメント カンパニー， エルエルシー 高血圧症を処置するためならびに脂質を下げるためのチアゾリジンジオン類似体
CN101448500A (zh) * 2006-03-16 2009-06-03 新陈代谢解决方案开发公司 噻唑烷二酮类似物和糖皮质激素激动剂的组合疗法
EP2540725A1 (de) * 2006-05-04 2013-01-02 Boehringer Ingelheim International GmbH Polymorphe von 1-((4-Methyl-chinazolin-2-yl)methyl)-3-methyl-7-(2-butin-1-yl)-8-(3-(R)-amino-piperidin-1-yl)xanthin
EP1852108A1 (en) * 2006-05-04 2007-11-07 Boehringer Ingelheim Pharma GmbH & Co.KG DPP IV inhibitor formulations
PE20080251A1 (es) 2006-05-04 2008-04-25 Boehringer Ingelheim Int Usos de inhibidores de dpp iv
EP2452683A3 (en) 2006-06-26 2012-08-22 Amgen Inc. Methods for treating atherosclerosis
KR100791399B1 (ko) 2006-09-06 2008-01-07 동우신테크 주식회사 염산 피오글리타존의 제조방법
EA200900392A1 (ru) 2006-09-07 2010-06-30 Никомед Гмбх Комбинированное лечение сахарного диабета
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
RU2009126633A (ru) * 2006-12-13 2011-01-20 Джилид Сайэнс, Инк. (US) Монофосфатные соединения, способ их получения, аэрозольный препарат (варианты) и способ профилактики и/или лечения бронхостеноза посредством указанных соединений
WO2008075380A2 (en) * 2006-12-21 2008-06-26 Ind-Swift Laboratories Limited Process for the preparation of thiazolidine derivatives
WO2008091624A2 (en) * 2007-01-22 2008-07-31 Teva Pharmaceutical Industries Ltd. Polymorphic forms of rosiglitazone hydrobromide and processes for preparation thereof
MY147596A (en) * 2007-02-01 2012-12-31 Takeda Pharmaceutical Solid preparation comprising alogliptin and pioglitazone
EP1988091B1 (en) 2007-02-07 2015-06-10 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
CL2008000684A1 (es) 2007-03-09 2008-08-01 Indigene Pharmaceuticals Inc Composicion farmaceutica que comprende metformina r-(+) lipoato y un inhibidor de reductasa hmg-coa; formulacion de dosis unitaria; y uso en el tratamiento de una complicacion diabetica.
US8093236B2 (en) * 2007-03-13 2012-01-10 Takeda Pharmaceuticals Company Limited Weekly administration of dipeptidyl peptidase inhibitors
KR101476472B1 (ko) * 2007-03-30 2015-01-05 암브룩스, 인코포레이티드 변형된 ｆｇｆ-21 폴리펩티드 및 그 용도
US20080249156A1 (en) * 2007-04-09 2008-10-09 Palepu Nageswara R Combinations of statins and anti-obesity agent and glitazones
US11241420B2 (en) 2007-04-11 2022-02-08 Omeros Corporation Compositions and methods for prophylaxis and treatment of addictions
US20160331729A9 (en) * 2007-04-11 2016-11-17 Omeros Corporation Compositions and methods for prophylaxis and treatment of addictions
MX2009010854A (es) 2007-04-11 2010-01-28 Omeros Corp Composiciones y metodos para profilaxis y tratamiento de adicciones.
PL2152663T3 (pl) 2007-06-04 2014-09-30 Ben Gurion Univ Of The Negev Research And Development Authority Związki triarylowe oraz kompozycje zawierające te związki
CA3089569C (en) 2007-06-04 2023-12-05 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
SI2489731T1 (sl) 2007-07-26 2014-12-31 Amgen Inc. Patent Operations, M/S 28-2-C Modificirani encimi lecitin-holesterol aciltransferaze
EP3542801A1 (en) * 2007-08-17 2019-09-25 Boehringer Ingelheim International GmbH Purin derivatives for use in the treatment of fap-related diseases
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
RU2486179C2 (ru) 2007-09-14 2013-06-27 МЕТАБОЛИК СОЛЮШНЗ ДЕВЕЛОПМЕНТ КОМПАНИ, ЭлЭлСи Аналоги тиазолидиндиона для лечения диабета и дислипидемии
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
PE20140960A1 (es) 2008-04-03 2014-08-15 Boehringer Ingelheim Int Formulaciones que comprenden un inhibidor de dpp4
WO2009133576A1 (en) * 2008-04-28 2009-11-05 Erregierre S.P.A. A process for the preparation of 4-[2-(5-ethyl-2-pyridyl)ethoxy]nitrobenzene and pioglitazone
PE20100156A1 (es) * 2008-06-03 2010-02-23 Boehringer Ingelheim Int Tratamiento de nafld
JP2011522828A (ja) 2008-06-04 2011-08-04 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 胃腸障害、炎症、癌、およびその他の障害の治療のために有用なグアニル酸シクラーゼのアゴニスト
EP2321341B1 (en) 2008-07-16 2017-02-22 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
UY32030A (es) 2008-08-06 2010-03-26 Boehringer Ingelheim Int "tratamiento para diabetes en pacientes inapropiados para terapia con metformina"
JP5559689B2 (ja) 2008-08-06 2014-07-23 協和発酵キリン株式会社 ３環系化合物
KR20190016601A (ko) 2008-08-06 2019-02-18 베링거 인겔하임 인터내셔날 게엠베하 메트포르민 요법이 부적합한 환자에서의 당뇨병 치료
US8846315B2 (en) 2008-08-12 2014-09-30 Zinfandel Pharmaceuticals, Inc. Disease risk factors and methods of use
ME01898B (me) * 2008-08-12 2014-12-20 Zinfandel Pharmaceuticals Inc Metoda za identifikaciju faktora rizika od alchajmerove bolesti
PE20110297A1 (es) * 2008-08-15 2011-05-26 Boehringer Ingelheim Int Inhibidores de dpp-4 para la cicatrizacion de heridas
CN102112444A (zh) * 2008-09-02 2011-06-29 株式会社德山 脱溴化氢化抑制剂
RU2011113823A (ru) 2008-09-10 2012-10-20 БЕРИНГЕР ИНГЕЛЬХАЙМ ИНТЕРНАЦИОНАЛЬ ГмбХ (DE) Комбинированная терапия, предназначенная для лечения диабета и связанных с ним состояний
WO2010041538A1 (ja) * 2008-10-10 2010-04-15 株式会社トクヤマ カルボニルオキシ化合物の製造方法
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
JP2012512848A (ja) 2008-12-23 2012-06-07 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 有機化合物の塩の形態
TW201036975A (en) 2009-01-07 2010-10-16 Boehringer Ingelheim Int Treatment for diabetes in patients with inadequate glycemic control despite metformin therapy
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
KR20170093264A (ko) 2009-03-11 2017-08-14 오메로스 코포레이션 중독의 예방 및 치료용 조성물 및 방법
CA2766033C (en) * 2009-06-25 2016-09-20 Alkermes, Inc. Prodrugs of nh-acidic compounds
WO2010151689A1 (en) 2009-06-25 2010-12-29 Alkermes, Inc. Heterocyclic compounds for the treatment of neurological and psychological disorders
US20110065756A1 (en) * 2009-09-17 2011-03-17 De Taeye Bart M Methods and compositions for treatment of obesity-related diseases
WO2011059053A1 (ja) 2009-11-13 2011-05-19 東レ株式会社 糖尿病の治療または予防薬
NZ599298A (en) 2009-11-27 2014-11-28 Boehringer Ingelheim Int Treatment of genotyped diabetic patients with dpp-iv inhibitors such as linagliptin
CA2783468C (en) 2009-12-15 2018-10-09 Metabolic Solutions Development Company, Llc 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
WO2011120923A1 (en) 2010-03-30 2011-10-06 Boehringer Ingelheim International Gmbh Pharmaceutical composition comprising an sglt2 inhibitor and a ppar- gamma agonist and uses thereof
JP6034781B2 (ja) 2010-05-05 2016-11-30 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 併用療法
EP3725325B1 (en) 2010-06-24 2023-05-31 Boehringer Ingelheim International GmbH Diabetes therapy
EP2611434A1 (en) 2010-09-01 2013-07-10 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
JP2014505055A (ja) 2011-01-10 2014-02-27 ジンファンデル ファーマシューティカルズ インコーポレイテッド アルツハイマー病を治療するための方法及び製剤
WO2012153312A1 (en) 2011-05-11 2012-11-15 Ranbaxy Laboratories Limited Process for the purification of pioglitazone
DK2731947T3 (en) 2011-07-15 2019-04-23 Boehringer Ingelheim Int SUBSTITUTED DIMERIC QUINAZOLINE DERIVATIVE, PREPARATION AND USE thereof IN PHARMACEUTICAL COMPOSITIONS FOR TREATMENT OF TYPE I AND TYPE II DIABETES
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
EP2788384B1 (en) 2011-12-08 2017-08-09 Amgen Inc. Agonistic human lcat antigen binding proteins and their use in therapy
EP2790734B1 (en) 2011-12-15 2019-02-20 Alkermes Pharma Ireland Limited Prodrugs of secondary amine compounds
US9504679B2 (en) 2011-12-19 2016-11-29 Bjoern Colin Kahrs Pharmaceutical compositions comprising glitazones and Nrf2 activators
US20130158077A1 (en) 2011-12-19 2013-06-20 Ares Trading S.A. Pharmaceutical compositions
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
EP2849755A1 (en) 2012-05-14 2015-03-25 Boehringer Ingelheim International GmbH A xanthine derivative as dpp -4 inhibitor for use in the treatment of 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
WO2014152843A1 (en) 2013-03-14 2014-09-25 Deuterx, Llc Deuterium-enriched 2,4-thiazolidinediones and methods of treatment
US20140275138A1 (en) * 2013-03-15 2014-09-18 Cba Pharma, Inc. Method and products for treating diabetes
US9486494B2 (en) 2013-03-15 2016-11-08 Synergy Pharmaceuticals, Inc. Compositions useful for the treatment of gastrointestinal disorders
EP2970384A1 (en) 2013-03-15 2016-01-20 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase and their uses
JP6606491B2 (ja) 2013-06-05 2019-11-13 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ｃの超高純度アゴニスト、その作成および使用方法
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
JP6657101B2 (ja) 2013-11-05 2020-03-04 ベン グリオン ユニバーシティ オブ ザ ネガフ リサーチ アンド ディベロップメント オーソリティ 糖尿病及びそれから生じる疾患合併症の治療のための化合物
EP3094328B1 (en) 2014-01-15 2020-08-19 Poxel SA 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
KR20240024362A (ko) 2014-10-24 2024-02-23 브리스톨-마이어스 스큅 컴퍼니 변형된 fgf-21 폴리펩티드 및 그의 용도
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
MY195671A (en) 2016-06-08 2023-02-03 Support Venture Gmbh Pharmaceutical Combinations for Treating Cancer
CA3022202A1 (en) 2016-06-10 2017-12-14 Boehringer Ingelheim International Gmbh Combinations of linagliptin and metformin
MA45981A (fr) 2016-08-17 2019-06-26 Support Venture Gmbh Méthode de prévention ou de traitement de la perte audititive.
TR201620309A2 (tr) 2016-12-30 2018-07-23 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Metformi̇n hi̇droklori̇t ve pi̇ogli̇tazon hi̇droklori̇ti̇n farmasöti̇k bi̇leşi̇mleri̇
SG10202110804WA (en) 2017-04-04 2021-11-29 Kinarus Ag Methods of preventing or treating ophthalmic diseases
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
CA3092335A1 (en) 2018-03-05 2019-09-12 Alkermes Pharma Ireland Limited Aripiprazole dosing strategy
CN112512586A (zh) 2018-07-13 2021-03-16 基纳鲁斯股份公司 用于预防或治疗纤维化疾病的ppar激动剂和p38激酶抑制剂的组合
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
US11767317B1 (en) 2020-06-30 2023-09-26 Poxel Sa Methods of synthesizing enantiopure deuterium-enriched pioglitazone
US11319313B2 (en) 2020-06-30 2022-05-03 Poxel Sa Crystalline forms of deuterium-enriched pioglitazone
EP4196120A1 (en) 2020-08-11 2023-06-21 Kinarus AG Methods of preventing or treating covid-19 and related viral diseases or disorders
TW202214230A (zh) 2020-09-30 2022-04-16 大陸商映恩生物製藥（蘇州）有限公司 一種抗腫瘤化合物及其製備方法和應用

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 (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Also Published As

Publication number Publication date
DE10199018I2 (de) 2006-02-02
AU5246786A (en) 1986-07-24
ZA86203B (en) 1987-09-30
NO860141L (no) 1986-07-21
HUT41775A (en) 1987-05-28
AU572719B2 (en) 1988-05-12
NL300038I2 (nl) 2001-05-01
PT81859A (en) 1986-02-01
SG105691G (en) 1992-02-14
JPS61267580A (ja) 1986-11-27
EP0193256A1 (en) 1986-09-03
FI81098C (fi) 1990-09-10
DK171614B1 (da) 1997-02-24
FI81098B (fi) 1990-05-31
DK21986A (da) 1986-07-20
CS407991A3 (en) 1992-04-15
JPH0566956B2 (zh) 1993-09-22
DK21986D0 (da) 1986-01-17
ES550986A0 (es) 1987-05-16
MX9202933A (es) 1992-06-30
PT81859B (pt) 1988-05-27
CA1277323C (en) 1990-12-04
KR860005811A (ko) 1986-08-13
NO163857C (no) 1990-08-01
AR240698A1 (es) 1990-09-28
FI860232A0 (fi) 1986-01-17
KR920010046B1 (ko) 1992-11-13
ES8705886A1 (es) 1987-05-16
IE58928B1 (en) 1993-12-01
DE3662689D1 (en) 1989-05-11
FI860232A (fi) 1986-07-20
EP0193256B1 (en) 1989-04-05
US4687777A (en) 1987-08-18
GR860124B (en) 1986-05-19
DE10199018I1 (de) 2001-07-12
HK3692A (en) 1992-01-17
ATE41931T1 (de) 1989-04-15
BR1100325A (pt) 2000-06-27
HU196795B (en) 1989-01-30
LU90719I2 (fr) 2001-03-26
NO163857B (no) 1990-04-23
IE860107L (en) 1986-07-19
LV5779A4 (lv) 1996-12-20
CN86100411A (zh) 1986-07-16
MY102016A (en) 1992-02-29
LV5779B4 (lv) 1997-04-20

Similar Documents

Publication Publication Date Title
CN1003934B (zh) 生产噻唑烷二酮的方法
CN101925584B (zh) 用于治疗哮喘、copd、过敏性鼻炎、过敏性结膜炎、特应性皮炎、癌症、乙型肝炎、丙型肝炎、hiv、hpv、细菌感染和皮肤病的嘧啶衍生物
US5741803A (en) Substituted thiazolidinedionle derivatives
CA2273147A1 (en) Substituted thiazolidinedione derivatives
CZ285984B6 (cs) Hydrochlorid monohydrátu 5-(2-(4-(1,2-benzisothia zol-3-yl)-1-piperazinyl)ethyl)-6-chlor-1,3-dihydr o-2H-indol-2-onu, způsob jeho přípravy a farmaceutický prostředek.
KR20060133095A (ko) Ｐｐａｒ(퍼옥시좀 증식자 활성화 수용체) 조절자로서의아릴 술폰아미드 및 술포닐기 화합물 및 대사성 장애의치료방법
JPS62277322A (ja) 安定化された腸溶性抗潰瘍固形組成物
JPH0390078A (ja) 新規化合物、その製法及びそれを含む医薬組成物
JPH02292272A (ja) 抗高血糖症剤として有用な新規ナフタレニルアルキル―３ｈ―１，２，３，５―オキサチアジアゾール２―オキシド類
AU2010312365A1 (en) Novel 3-hydroxy-5-arylisoxazole derivative
EP3275867A1 (en) Condensed ring derivative, and preparation method, intermediate, pharmaceutical composition and use thereof
EP0356214A2 (en) Thiazolidine dione derivatives
WO1993021166A1 (en) Heterocyclic compounds and their use in the treatment of type ii-diabetes
CN112996529A (zh) Matriptase 2抑制剂及其用途
CA2065799C (en) Thiazolidinedione derivatives, their production and their use
RU2140916C1 (ru) Феноксиалкилтиадиазолы, фармацевтическая композиция, способ профилактики и лечения пикорнавирусной инфекции и способ борьбы с пикорнавирусами
US4378359A (en) Theophyllinylmethyldioxolane derivatives, methods for their preparation and pharmaceutical compositions containing them
EP2634184B1 (en) C-arylglucoside derivative, preparation method therefor, and use thereof
CN1003589B (zh) 含n，n′-甲撑-双(2-氨基-5-巯基-1，3，4-噻二唑)活性组分的组合物及其制备方法和应用
CN108440440B (zh) 一种含萘环的1,2,4-噁二唑-肉桂酰哌嗪型化合物及其制法和用途
EP0034263B1 (en) Substituted benzonitriles and compositions for inhibiting viruses
CN1005630B (zh) 碱性硫醚及其盐酸盐的制备方法
NO152436B (no) Haarfargemiddel
GB2069493A (en) Pyridine derivatives
IE43095B1 (en) Novel anthelmintic therapy

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