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1. 发明公开

EP2452931A2 METHOD FOR PREPARING TRICYCLIC DERIVATIVES 有权转让
标题翻译：用于生产三环衍生物
公开(公告)号：EP2452931A2
公开(公告)日：2012-05-16
申请号：EP10797254.9
申请日：2010-06-29
申请人： Jeil Pharmaceutical Co., Ltd.
发明人： KIM, Myung-Hwa , YE, In-Hae , CHOI, Jong-Hee
IPC分类号： C07C231/02 , C07C237/38 , C07C51/367 , C07C63/68
CPC分类号： C07C319/20 , C07C51/06 , C07C65/01 , C07C67/08 , C07C67/30 , C07C233/65 , C07C235/42 , C07C2603/34 , C07D295/192 , C07C323/42 , C07C69/76
摘要： The present invention relates to a method for preparing a tricyclic derivative, and more particulary, to a method for preparing a tricyclic derivative inetermediate with high yield and purity, the method including: introducing a hydroxy group by esterifying and substituting 2-fluoroisophthalic acid compound; introducing a piperidyl group; introducing a hydroxy group through reduction reaction; and then hydrolyzing the resultant compound, and to a method for preparing the tricyclic derivative using said intermediate. According to the method of the present invention, it is possible to provide a tricyclic derivative and an intermediate thereof with high productivity and economic feasibility as well as high purity and yield, by purifying a compound using re-crystallization unlike typical methods of using column chromatography. In addition, the method of the present invention can be usefully used for industrial mass production because sodium borohydride or lithium aluminum hydride with low risk of a fire is used unlike typical methods of using lithium borohydride which is not industrially applicable due to high risk of a fire.

3. 发明公开

EP1646608A4 TRICYCLIC DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, THEIR PREPARATIONS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM 有权
标题翻译：三环衍生物或盐的药物UNNBEDENKLICHE，生产，药品成分含
公开(公告)号：EP1646608A4
公开(公告)日：2006-11-22
申请号：EP04773996
申请日：2004-06-23
申请人： JE IL PHARMACEUTICAL CO LTD
发明人： KIM MYUNG-HWA , CHUN KWANGWOO , CHOI JAE-WON , JOE BO-YOUNG , PARK SANG-WOO , KIM KWANG HEE , OH BYUNG-KYU , CHOI JONG-HEE
IPC分类号： C07C317/30 , C07C323/41 , C07C381/00 , C07D213/81 , C07D213/82 , C07D307/68 , C07D333/38
CPC分类号： C07C323/41 , C07C381/00 , C07C2601/08 , C07C2603/34 , C07D213/81 , C07D213/82 , C07D307/68 , C07D333/38

4. 发明公开

EP0827741A2 Composition for transdermal delivery system containing nonsteroidal anti-inflammatory drug as an active ingredient 失效
标题翻译：系统治疗系统系统NSAID als aktiveKomponente
公开(公告)号：EP0827741A2
公开(公告)日：1998-03-11
申请号：EP97115071.9
申请日：1997-08-30
申请人： JE IL Pharmaceutical Co., Ltd.
发明人： Choi, Hoo Kyun , Cho, Young Ju
IPC分类号： A61K9/70 , A61K31/19
CPC分类号： A61K9/7053 , A61K9/7092 , A61K31/192
摘要： This invention relates to a composition for transdermal delivery system containing a non-steroidal anti-inflammatory drug such as propionic acid derivatives (ketoprofen, etc.) and more particularly, to an improved composition for transdermal delivery system wherein said non-steroidal anti-inflammatory drug is dispersed in nonpolar polymers designed to continuously maximize thermodynamic activity and further to increase the skin permeability of said active ingredient using fatty acid, fatty acid ester, fatty acid alcohol, propylene glycol, propylene glycol fatty acid ester, oleic acid, olein alcohol, ethylene glycol monoethylether or its mixture as a solubilizing agent or permeation enhancer, if deemed necessary.
摘要翻译：本发明涉及一种包含非甾体抗炎药物如丙酮酸衍生物（酮洛芬等）的透皮给药系统组合物，更具体地说，涉及用于透皮给药系统的改进组合物，其中所述非甾体抗炎药药物分散在非极性聚合物中，其设计为连续地最大化热力学活性，并进一步增加所述活性成分的使用脂肪酸，脂肪酸酯，脂肪酸醇，丙二醇，丙二醇脂肪酸酯，油酸，油精醇，乙二醇单乙醚或其混合物作为增溶剂或渗透增强剂，如果认为必要的话。

5. 发明授权

EP2452931B1 METHOD FOR PREPARING TRICYCLIC DERIVATIVES 有权转让
标题翻译：制备三环衍生物的方法
公开(公告)号：EP2452931B1
公开(公告)日：2017-05-17
申请号：EP10797254.9
申请日：2010-06-29
申请人： JE IL Pharmaceutical Co., Ltd.
发明人： KIM, Myung-Hwa , YE, In-Hae , CHOI, Jong-Hee
IPC分类号： C07C51/367 , C07C63/68 , C07C319/20 , C07C323/42 , C07C233/65 , C07C235/42 , C07D211/06
CPC分类号： C07C319/20 , C07C51/06 , C07C65/01 , C07C67/08 , C07C67/30 , C07C233/65 , C07C235/42 , C07C2603/34 , C07D295/192 , C07C323/42 , C07C69/76

6. 发明授权

EP1646608B1 TRICYCLIC DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, THEIR PREPARATIONS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM 有权
标题翻译：三环衍生物或盐的药物UNNBEDENKLICHE，生产，药品成分含
公开(公告)号：EP1646608B1
公开(公告)日：2011-03-02
申请号：EP04773996.6
申请日：2004-06-23
申请人： JE IL Pharmaceutical Co., Ltd.
发明人： KIM, Myung-Hwa , CHUN, Kwangwoo , CHOI, Jae-Won , JOE, Bo-Young , PARK, Sang-Woo , KIM, Kwang Hee , OH, Byung-Kyu , CHOI, Jong-Hee
IPC分类号： C07C317/30
CPC分类号： C07C323/41 , C07C381/00 , C07C2601/08 , C07C2603/34 , C07D213/81 , C07D213/82 , C07D307/68 , C07D333/38
摘要： The present invention relates to tricyclic derivatives or pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. More precisely, the present invention relates to tricyclic derivatives as colchicine derivatives, pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. Tricyclic derivatives of the present invention show very powerful cytotoxicity to cancer cell lines but were much less toxic than colchicine or taxol, confirmed through animal toxicity test. Tricyclic derivatives of the invention also decrease the volume and weight of a tumor and have a strong angiogenesis inhibiting activity in HUVEC cells. Thus, tricyclic derivatives of the present invention can effectively be used as an anticancer agent, anti-proliferation agent and an angiogenesis inhibitor.

7. 发明公开

EP2452931A4 METHOD FOR PREPARING TRICYCLIC DERIVATIVES 有权转让
标题翻译： VERFAHREN ZUR HERSTELLUNG TRIZYKLISCHER DERIVATE
公开(公告)号：EP2452931A4
公开(公告)日：2013-12-25
申请号：EP10797254
申请日：2010-06-29
申请人： JEIL PHARMACEUTICAL CO LTD
发明人： KIM MYUNG-HWA , YE IN-HAE , CHOI JONG-HEE
IPC分类号： C07C51/367 , C07C63/68 , C07C233/65 , C07C235/42 , C07C319/20 , C07C323/42 , C07D211/06
CPC分类号： C07C319/20 , C07C51/06 , C07C65/01 , C07C67/08 , C07C67/30 , C07C233/65 , C07C235/42 , C07C2603/34 , C07D295/192 , C07C323/42 , C07C69/76
摘要： The present invention relates to a method for preparing a tricyclic derivative, and more particulary, to a method for preparing a tricyclic derivative inetermediate with high yield and purity, the method including: introducing a hydroxy group by esterifying and substituting 2-fluoroisophthalic acid compound; introducing a piperidyl group; introducing a hydroxy group through reduction reaction; and then hydrolyzing the resultant compound, and to a method for preparing the tricyclic derivative using said intermediate. According to the method of the present invention, it is possible to provide a tricyclic derivative and an intermediate thereof with high productivity and economic feasibility as well as high purity and yield, by purifying a compound using re-crystallization unlike typical methods of using column chromatography. In addition, the method of the present invention can be usefully used for industrial mass production because sodium borohydride or lithium aluminum hydride with low risk of a fire is used unlike typical methods of using lithium borohydride which is not industrially applicable due to high risk of a fire.
摘要翻译：本发明涉及一种制备三环衍生物的方法，更具体地说，涉及一种以高产率和纯度制备三环衍生物三烯衍生物的方法，所述方法包括：通过酯化和取代2-氟间苯二甲酸化合物引入羟基; 引入哌啶基; 通过还原反应引入羟基; 然后水解所得化合物，以及使用所述中间体制备三环衍生物的方法。根据本发明的方法，通过使用重结晶纯化化合物，可以提供具有高生产率和经济可行性以及高纯度和收率的三环衍生物及其中间体，与使用柱色谱法的典型方法不同。此外，本发明的方法可以有用地用于工业批量生产，因为使用低的火焰危险的硼氢化钠或氢化铝锂不同于使用硼氢化锂的典型方法，因为硼氢化锂不是工业上适用的，因为高风险火。

8. 发明公开

EP1756036A1 INDENE DERIVATIVES AND PROCESS FOR THE PREPARATION THEREOF 审中-公开
标题翻译： INDEN衍生物和方法及其
公开(公告)号：EP1756036A1
公开(公告)日：2007-02-28
申请号：EP05733516.8
申请日：2005-04-12
申请人： KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY , JE IL Pharmaceutical Co., Ltd. , Korea Research Institute of Bioscience and Biotechnology , CJ Corp.
发明人： CHEON, Hyae Gyeong , YOO, Sung-Eun , KIM, Sung Soo , YANG, Sung-Don , KIM, Kwang-Rok , RHEE, Sang Dal , AHN, Jin Hee , KANG, Seung Kyu , JUNG, Won Hoon , PARK, Sung Dae , KIM, Nam Gee , KIM, Sun Mee , MO, Kil Woong , LEE, Jae Mok , KANG, Hye Jung , LEE, Koun Ho , KIM, Jong Hoon , LEE, Jeong-Hyung , KIM, Seung Jun
IPC分类号： C07C69/753
CPC分类号： C07D295/088 , C07C65/26 , C07C69/757 , C07C229/50 , C07C233/52 , C07C255/47 , C07C2601/14 , C07C2602/08 , C07D295/155
摘要： The inventive indene derivatives of formula (I) are capable of selectively modulating the activities of peroxisome proliferator activated receptors (PPARs), causing no adverse side effects, and thus, they are useful for the treatment and prevention of disorders modulated by PPARs, i.e., metabolic syndromes such as diabetes, obesity, arteriosclerosis, hyperlipidemia, hyperinsulinism and hypertension, inflammatory diseases such as osteoporosis, liver cirrhosis and asthma, and cancer.

9. 发明公开

EP1646608A1 TRICYCLIC DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, THEIR PREPARATIONS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM 有权
标题翻译：三环衍生物或其药学上可接受的盐，它们的制剂和含有它们的药物组合物
公开(公告)号：EP1646608A1
公开(公告)日：2006-04-19
申请号：EP04773996.6
申请日：2004-06-23
申请人： JE IL Pharmaceutical Co., Ltd.
发明人： KIM, Myung-Hwa , CHUN, Kwangwoo , CHOI, Jae-Won , JOE, Bo-Young , PARK, Sang-Woo , KIM, Kwang Hee , OH, Byung-Kyu , CHOI, Jong-Hee
IPC分类号： C07C317/30
CPC分类号： C07C323/41 , C07C381/00 , C07C2601/08 , C07C2603/34 , C07D213/81 , C07D213/82 , C07D307/68 , C07D333/38
摘要： The present invention relates to tricyclic derivatives or pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. More precisely, the present invention relates to tricyclic derivatives as colchicine derivatives, pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. Tricyclic derivatives of the present invention show very powerful cytotoxicity to cancer cell lines but were much less toxic than colchicine or taxol, confirmed through animal toxicity test. Tricyclic derivatives of the invention also decrease the volume and weight of a tumor and have a strong angiogenesis inhibiting activity in HUVEC cells. Thus, tricyclic derivatives of the present invention can effectively be used as an anticancer agent, anti-proliferation agent and an angiogenesis inhibitor.
摘要翻译：本发明涉及三环衍生物或其药学上可接受的盐，它们的制剂和含有它们的药物组合物。更确切地说，本发明涉及作为秋水仙碱衍生物的三环衍生物，其药学上可接受的盐，其制剂和含有它们的药物组合物。本发明的三环衍生物对癌细胞系显示非常强的细胞毒性，但通过动物毒性试验证实，其毒性比秋水仙碱或紫杉醇低得多。本发明的三环衍生物还降低肿瘤的体积和重量并且在HUVEC细胞中具有强的血管生成抑制活性。因此，本发明的三环衍生物可以有效地用作抗癌剂，抗增殖剂和血管生成抑制剂。

10. 发明公开

EP0827741A3 Composition for transdermal delivery system containing nonsteroidal anti-inflammatory drug as an active ingredient 失效
标题翻译：对于含有NSAID作为活性成分透皮治疗系统准备
公开(公告)号：EP0827741A3
公开(公告)日：1999-12-29
申请号：EP97115071.9
申请日：1997-08-30
申请人： JE IL Pharmaceutical Co., Ltd.
发明人： Choi, Hoo Kyun , Cho, Young Ju
IPC分类号： A61K9/70 , A61K31/19
CPC分类号： A61K9/7053 , A61K9/7092 , A61K31/192
摘要： This invention relates to a composition for transdermal delivery system containing a non-steroidal anti-inflammatory drug such as propionic acid derivatives (ketoprofen, etc.) and more particularly, to an improved composition for transdermal delivery system wherein said non-steroidal anti-inflammatory drug is dispersed in nonpolar polymers designed to continuously maximize thermodynamic activity and further to increase the skin permeability of said active ingredient using fatty acid, fatty acid ester, fatty acid alcohol, propylene glycol, propylene glycol fatty acid ester, oleic acid, olein alcohol, ethylene glycol monoethylether or its mixture as a solubilizing agent or permeation enhancer, if deemed necessary.

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