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1. 发明申请

WO2004089962A2 NEW CARBAMOYL-AND THIOCARBAMOYL-PHOSPHONATES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM 审中-公开
标题翻译：新型碳水化合物和硫代磷酸酯和包含它们的药物组合物
公开(公告)号：WO2004089962A2
公开(公告)日：2004-10-21
申请号：PCT/IL2004/000302
申请日：2004-04-01
申请人： YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM , BREUER, Eli , REICH, Reuven , GOLOMB, Gershon , KATZ, Yiffat
发明人： BREUER, Eli , REICH, Reuven , GOLOMB, Gershon , KATZ, Yiffat
IPC分类号： C07F9/38
CPC分类号： C07F9/4065 , C07F9/3891
摘要： The present invention provides a compound of the following formula (I): R 3 -NH-C(=X)-P(=O)OR 1 OR 2 including pharmaceutically acceptable salts, solvates, hydrates and polymorphs of the compounds of formula I, as well as geometrical isomers and optically active forms of the compounds of formula I and pharmaceutically acceptable salts, solvates, hydrates and polymorphs of said isomers and forms, wherein R' and R 2 may be the same or different and are each selected from hydrogen, acyloxyalkyl and aryl or R 1 and R 2 may form together with the oxygen and phosphorus atoms a dioxaphosphacycloalkane ring; X is 0 or S; and R 3 is selected, when X is 0, from bicycloalkyl, cycloalkylalkyl and substituted cycloalkyl by at least one of alkyl, amino, amidino and guanidino; and R 3 is selected, when X is S, from bicycloalkyl, cycloalkylalkyl and cycloalkyl optionally substituted by at least one of alkyl, amino, amidino and guanidino; with the proviso that when X is O, R 3 is not cyclohexylmethyl, and when X is S, R 3 is not cyclohexyl. The invention further provides pharmaceutical compositions comprising the above compounds and their use in medicine.
摘要翻译：本发明提供下列化学式（I）的化合物：R 3 -NH-C（= X）-P（= O）OR 1或OR 2，包括其药学上可接受的盐，溶剂合物，水合物和多晶型物的式I化合物，以及式I化合物的几何异构体和光学活性形式以及所述异构体和形式的药学上可接受的盐，溶剂合物，水合物和多晶型物，其中R'和R 2可以相同或不同的，并且各自选自氢，酰氧基烷基和芳基，或者R 1和R 2可以与氧和磷原子一起形成二氧杂环磷杂环烷环; X为0或S; 当X为0时，R 3选自烷基，氨基，脒基和胍基中的至少一个来自双环烷基，环烷基烷基和取代的环烷基; 并且当X为S时，选自R 3选自二烷基，环烷基烷基和任选被烷基，氨基，脒基和胍基中的至少一个取代的环烷基; 条件是当X是O时，R 3不是环己基甲基，当X是S时，R 3不是环己基。本发明还提供了包含上述化合物及其在药物中的用途的药物组合物。

2. 发明申请

WO2010089752A1 CARJBAMOYLPHOSPHONATES AS INHIBITORS AND USES THEREOF 审中-公开
标题翻译：作为抑制剂及其用途的碳酰氨基磷酸酯
公开(公告)号：WO2010089752A1
公开(公告)日：2010-08-12
申请号：PCT/IL2010/000115
申请日：2010-02-09
申请人： YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM, LTD. , BREUER, Eli , REICH, Reuven , FRANT, Julia , HOFFMAN, Amnon , AINELLY, Veerendhar
发明人： BREUER, Eli , REICH, Reuven , FRANT, Julia , HOFFMAN, Amnon , AINELLY, Veerendhar
IPC分类号： A61K31/662 , C07F9/38 , C07F9/40 , A61P35/00
CPC分类号： A61K31/662 , C07F9/3891 , C07F9/4065
摘要： The present invention relates to novel metalloproteinase inhibitors having an aryloxybenzenesulfonamide moiety and a carbamoylphosphonic acid moiety, to pharmaceutical compositions comprising them, and to their uses in the prevention and/or treatment of disease or disorder associated with MMP.
摘要翻译：本发明涉及具有芳氧基苯磺酰胺部分和氨基甲酰基膦酸部分的新型金属蛋白酶抑制剂，包含它们的药物组合物，以及其在预防和/或治疗与MMP相关的疾病或病症中的用途。

3. 发明公开

EP1223945A1 COMPOSITIONS COMPRISING OXOPHOSPHONATE-BASED METALLOPROTEINASE INHIBITORS 审中-公开
标题翻译：金属蛋白酶抑制剂含CARBAMOYLPHOSPHONATE用于癌症的治疗
公开(公告)号：EP1223945A1
公开(公告)日：2002-07-24
申请号：EP00962786.0
申请日：2000-09-19
申请人： YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM
发明人： BREUER, Eli , REICH, Reuven , SALOMON, Claudio
IPC分类号： A61K31/662 , A61P35/00 , A61P19/02 , C07F9/38 , C07K5/062 , C07K5/065 , A61K38/05 , C07F9/40 , C07F9/59 , C07F9/6533 , C07F9/572
CPC分类号： A61K31/662 , A61K31/675 , A61K38/00 , A61K47/64 , A61K49/0008 , C07F9/3891 , C07F9/4065 , C07F9/5721 , C07F9/591 , C07F9/6533 , C07K5/06191
摘要： The present invention relates to compositions useful for treating or controlling disease states or conditions associated with zinc containing proteinases, especially metalloproteinases. The active ingredient in these compositions is an alpha-oxo- or alpha-thioxophosphonate of formula (I). Out of the phosphonates of formula (I), some are known and others are new. The novel compounds constitute another aspect of the invention.

4. 发明授权

EP2393495B1 CARBAMOYLPHOSPHONATES AS INHIBITORS AND USES THEREOF 有权
标题翻译： CARBAMOYLPHOSPHONATES作为抑制剂及其用途
公开(公告)号：EP2393495B1
公开(公告)日：2014-07-23
申请号：EP10706757.1
申请日：2010-02-09
申请人： Yissum Research Development Company of the Hebrew University of Jerusalem, Ltd.
发明人： BREUER, Eli , REICH, Reuven , FRANT, Julia , HOFFMAN, Amnon , AINELLY, Veerendhar
IPC分类号： A61K31/662 , C07F9/38 , C07F9/40 , A61P35/00
CPC分类号： A61K31/662 , C07F9/3891 , C07F9/4065

5. 发明公开

EP1471870A2 USE OF LIPID CONJUGATES IN THE TREATMENT OF DISEASE 有权
标题翻译：脂质结合物的疾病中的治疗
公开(公告)号：EP1471870A2
公开(公告)日：2004-11-03
申请号：EP01900237.7
申请日：2001-01-10
申请人： YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM
发明人： YEDGAR, Saul , SHOSEYOV, David , GOLOMB, Gershon , REICH, Reuven , GINSBURG, Isaac , HIGAZI, Abd-Al-Roof , LIGUMSKI, Moshe , KRIMSKY, Miron , OJCIUS, David , YARD, Benito, Antonio , VAN DER WOUDE, Fokko, Johannes , SCHNITZER, Edit
IPC分类号： A61K6/00
CPC分类号： A61K47/544
摘要： The invention provides novel methods for treating disease based on the medicinal use of lipids and phospholipids covalently bound to physiologically acceptable monomers or polymers. Phosphatidylethanolamine moieties conjugated to physiologically acceptable monomers and polymers (PE conjugates) manifest an unexpectedly wide range of pharmacological effects, including stabilizing cell membranes; limiting oxidative damage to cell and blood components; limiting cell proliferation, cell extravasation and(tumor) cell migratory behavior; suppressing immune responses; and attenuating physiological reactions to stress, as expressed in elevated chemokine levels.

6. 发明授权

EP1471870B1 USE OF LIPID CONJUGATES IN THE TREATMENT OF DISEASE 有权
标题翻译：脂质结合物的疾病中的治疗
公开(公告)号：EP1471870B1
公开(公告)日：2014-08-20
申请号：EP01900237.7
申请日：2001-01-10
申请人： Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.
发明人： YEDGAR, Saul , SHOSEYOV, David , GOLOMB, Gershon , REICH, Reuven , GINSBURG, Isaac , HIGAZI, Abd-Al-Roof , LIGUMSKI, Moshe , KRIMSKY, Miron , OJCIUS, David , YARD, Benito, Antonio , VAN DER WOUDE, Fokko, Johannes , SCHNITZER, Edit
IPC分类号： A61K31/70 , A61K31/715 , A61K31/727 , A61K31/695 , C07H5/04 , C07H5/06 , C07H21/00 , C07H13/04 , C08B37/08 , C08B37/10 , A61K47/48
CPC分类号： A61K47/544

7. 发明公开

EP2393495A1 CARJBAMOYLPHOSPHONATES AS INHIBITORS AND USES THEREOF 有权
标题翻译： CARBAMOYLPHOSPHONATES作为抑制剂及其用途
公开(公告)号：EP2393495A1
公开(公告)日：2011-12-14
申请号：EP10706757.1
申请日：2010-02-09
申请人： Yissum Research Development Company of the Hebrew University of Jerusalem, Ltd.
发明人： BREUER, Eli , REICH, Reuven , FRANT, Julia , HOFFMAN, Amnon , AINELLY, Veerendhar
IPC分类号： A61K31/662 , C07F9/38 , C07F9/40 , A61P35/00
CPC分类号： A61K31/662 , C07F9/3891 , C07F9/4065
摘要： The present invention relates to novel metalloproteinase inhibitors having an aryloxybenzenesulfonamide moiety and a carbamoylphosphonic acid moiety, to pharmaceutical compositions comprising them, and to their uses in the prevention and/or treatment of disease or disorder associated with MMP.

8. 发明公开

EP1611143A2 NEW CARBAMOYL-AND THIOCARBAMOYL-PHOSPHONATES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM 审中-公开
标题翻译：氨基甲酰基和硫代磷酸酯和含有药物组合物
公开(公告)号：EP1611143A2
公开(公告)日：2006-01-04
申请号：EP04725138.4
申请日：2004-04-01
申请人： YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM
发明人： BREUER, Eli , REICH, Reuven , GOLOMB, Gershon , KATZ, Yiffat
IPC分类号： C07F9/38 , C07F9/40 , A61K31/662 , A61P19/02 , A61P35/00
CPC分类号： C07F9/4065 , C07F9/3891
摘要： The present invention provides a compound of the following formula (I): R3-NH-C(=X)-P(=O)OR1OR2 including pharmaceutically acceptable salts, solvates, hydrates and polymorphs of the compounds of formula I, as well as geometrical isomers and optically active forms of the compounds of formula I and pharmaceutically acceptable salts, solvates, hydrates and polymorphs of said isomers and forms, wherein R' and R2 may be the same or different and are each selected from hydrogen, acyloxyalkyl and aryl or R1 and R2 may form together with the oxygen and phosphorus atoms a dioxaphosphacycloalkane ring; X is 0 or S; and R3 is selected, when X is 0, from bicycloalkyl, cycloalkylalkyl and substituted cycloalkyl by at least one of alkyl, amino, amidino and guanidino; and R3 is selected, when X is S, from bicycloalkyl, cycloalkylalkyl and cycloalkyl optionally substituted by at least one of alkyl, amino, amidino and guanidino; with the proviso that when X is O, R3 is not cyclohexylmethyl, and when X is S, R3 is not cyclohexyl. The invention further provides pharmaceutical compositions comprising the above compounds and their use in medicine.

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