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1. 发明授权

US06683103B2 Sulfonamides for treatment of endothelin-mediated disorders 失效
标题翻译：磺酰胺用于治疗内皮素介导的疾病
公开(公告)号：US06683103B2
公开(公告)日：2004-01-27
申请号：US10029561
申请日：2001-12-20
申请人： Chengde Wu , Natalie Blok , Timothy Kogan , Karin Keller
发明人： Chengde Wu , Natalie Blok , Timothy Kogan , Karin Keller
IPC分类号： A61K3142
CPC分类号： C07D413/14 , C07D261/16 , C07D409/12 , C07D413/12 , C07D417/14
摘要： Thienylsulfonamides and their pharmaceutically acceptable derivatives, pharmaceutical compositions, articles of manufacture, combinations, lyophilized powders and methods for the treatment of endothelin diseases using these formulations and sulfonamides are provided. A process of preparing an alkali metal salt of a hydrophobic sulfonamide is provided. The process includes the step of dissolving a free sulfonamide in an organic solvent in the presence of a saturated alkali metal salt solution and recovering the formed sulfonamide salt from the organic phase.
摘要翻译：提供噻吩磺酰胺及其药学上可接受的衍生物，药物组合物，制品，组合，冻干粉末以及使用这些制剂和磺酰胺治疗内皮素疾病的方法。提供了制备疏水性磺酰胺的碱金属盐的方法。该方法包括在饱和碱金属盐溶液存在下将游离磺酰胺溶解在有机溶剂中并从有机相中回收所形成的磺酰胺盐的步骤。

2. 发明授权

US06458805B2 Formulation of sulfonamides for treatment of endothelin-mediated disorders 失效
标题翻译：用于治疗内皮素介导的疾病的磺酰胺的制剂
公开(公告)号：US06458805B2
公开(公告)日：2002-10-01
申请号：US09792237
申请日：2001-02-23
申请人： Natalie Blok , Chengde Wu , Patricia Woodard , Karin Keller , Timothy Kogan
发明人： Natalie Blok , Chengde Wu , Patricia Woodard , Karin Keller , Timothy Kogan
IPC分类号： A61K3147
CPC分类号： C07D413/14 , C07D261/16 , C07D409/12 , C07D413/12 , C07D417/14
摘要： Formulations of pharmaceutically-acceptable salts of thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides using the formulations are provided. In particular, formulations of sodium salts of N-(isoxazolyl)-thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)-pyrrolylsulfonamides and methods using these sulfonamide salts for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide salt are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamide salts or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.
摘要翻译：提供噻吩基，呋喃基和吡咯基磺酰胺的药学上可接受的盐的制剂以及使用制剂调节或改变肽内皮素家族的活性的方法。特别地，N-（异恶唑基） - 噻吩基磺酰胺，N-（异恶唑基）呋喃基磺酰胺和N-（异恶唑基） - 吡咯烷磺酰胺的钠盐的制剂和使用这些磺酰胺盐的方法，用于通过接触来抑制内皮素肽与内皮素受体的结合提供了具有磺酰胺盐的受体。还提供了通过施用有效量的一种或多种这些抑制或增加内皮素活性的磺酰胺盐或其前体来治疗内皮素介导的病症的方法。

3. 发明授权

US06432994B1 Sulfonamides for treatment of endothelin-mediated disorders 有权
标题翻译：磺酰胺用于治疗内皮素介导的疾病
公开(公告)号：US06432994B1
公开(公告)日：2002-08-13
申请号：US09403599
申请日：2000-03-27
申请人： Chengde Wu , Natalie Blok , Timothy Kogan , Karin Keller , Patricia Woodard
发明人： Chengde Wu , Natalie Blok , Timothy Kogan , Karin Keller , Patricia Woodard
IPC分类号： A61K3142
CPC分类号： C07D413/14 , C07D261/16 , C07D409/12 , C07D413/12 , C07D417/14
摘要： Thienyl-, furyl- and pyrrolyl-sulfonamides, pharmaceutically-acceptable salts of sulfonamides, formulations of salts and the sulfonamides, and methods for modulating or altering the activity of the endothelin family of peptides using the formulations and sulfonamides are provided. In particular, formulations of sodium salts of N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides are provided. A process of preparing an alkali metal salt of a hydrophobic sulfonamide is provided. The process includes the step of dissolving a free sulfonamide in an organic solvent in the presence of a saturated alkali metal salt solution and recovering the formed sulfonamide salt from the organic phase.
摘要翻译：提供噻吩基，呋喃基和吡咯基磺酰胺，磺酰胺的药学上可接受的盐，盐和磺酰胺的制剂，以及使用制剂和磺酰胺调节或改变肽的内皮素家族的活性的方法。特别地，提供了N-（异恶唑基）噻吩基磺酰胺，N-（异恶唑基）呋喃基磺酰胺和N-（异恶唑基）吡咯烷基磺酰胺的钠盐的配方。提供了制备疏水性磺酰胺的碱金属盐的方法。该方法包括在饱和碱金属盐溶液存在下将游离磺酰胺溶解在有机溶剂中并从有机相中回收所形成的磺酰胺盐的步骤。

4. 发明授权

US06248767B1 Formulation of sulfonamides for treatment of endothelin-mediated disorders 失效
标题翻译：用于治疗内皮素介导的疾病的磺酰胺的制剂
公开(公告)号：US06248767B1
公开(公告)日：2001-06-19
申请号：US08938444
申请日：1997-09-26
申请人： Natalie Blok , Chengde Wu , Patricia Woodard , Karin Keller , Timothy Kogan
发明人： Natalie Blok , Chengde Wu , Patricia Woodard , Karin Keller , Timothy Kogan
IPC分类号： A61K3142
CPC分类号： C07D413/14 , C07D261/16 , C07D409/12 , C07D413/12 , C07D417/14
摘要： Formulations of pharmaceutically-acceptable salts of thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides using the formulations are provided. In particular, formulations of sodium salts of N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamide salts for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide salt are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamide salts or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.
摘要翻译：提供噻吩基，呋喃基和吡咯基磺酰胺的药学上可接受的盐的制剂以及使用制剂调节或改变肽的内皮素家族的活性的方法。特别地，N-（异恶唑基）噻吩基磺酰胺，N-（异恶唑基）呋喃基磺酰胺和N-（异恶唑基）吡咯烷磺酰胺的钠盐的制剂和使用这些磺酰胺盐通过使受体接触来抑制内皮素肽与内皮素受体结合的方法与磺酰胺盐。还提供了通过施用有效量的一种或多种这些抑制或增加内皮素活性的磺酰胺盐或其前体来治疗内皮素介导的病症的方法。

5. 发明授权

US5783705A Process of preparing alkali metal salys of hydrophobic sulfonamides 失效
标题翻译：制备疏水性磺胺类碱金属盐的工艺
公开(公告)号：US5783705A
公开(公告)日：1998-07-21
申请号：US847797
申请日：1997-04-28
申请人： Natalie Blok , Chengde Wu , Karin Keller , Timothy P. Kogan
发明人： Natalie Blok , Chengde Wu , Karin Keller , Timothy P. Kogan
IPC分类号： A61P9/00 , A61P11/00 , C07D261/16 , C07D409/12 , C07D413/12 , C07D413/14 , C07D417/14 , C07D261/06 , C07D261/04 , C07D261/14
CPC分类号： C07D413/14 , C07D261/16 , C07D409/12 , C07D413/12 , C07D417/14
摘要： A process of preparing an alkali metal salt of a hydrophobic sulfonamide is provided. The process includes the step of dissolving a free sulfonamide in an organic solvent in the presence of a saturated alkali metal salt solution and recovering the formed sulfonamide salt from the organic phase.
摘要翻译：提供了制备疏水性磺酰胺的碱金属盐的方法。该方法包括在饱和碱金属盐溶液存在下将游离磺酰胺溶解在有机溶剂中并从有机相中回收所形成的磺酰胺盐的步骤。

6. 发明授权

US5444050A Binding of E-selectin or P-selectin to sialyl Lewis.sup.x or sialyl-Lewis.sup.a 失效
公开(公告)号：US5444050A
公开(公告)日：1995-08-22
申请号：US235293
申请日：1994-04-29
申请人： Timothy P. Kogan , Brian Dupre , Ian L. Scott , Karin Keller , Huong Dao , Pamela J. Beck
发明人： Timothy P. Kogan , Brian Dupre , Ian L. Scott , Karin Keller , Huong Dao , Pamela J. Beck
IPC分类号： A61K31/70 , A61K31/7028 , A61K31/7034 , A61P1/00 , A61P9/00 , A61P11/08 , A61P17/00 , A61P29/00 , A61P35/00 , A61P37/06 , C07H15/18 , C07H15/203 , C07H15/20
CPC分类号： C07H15/18 , C07H15/203
摘要： This invention relates to compounds that inhibit the binding of E-selectin and/or P-selectin to sialyl-Lewis.sup.x or sialyl-Lewis.sup.a presented on a cell surface having the general structure ##STR1## wherein X is selected from the group consisting of --(CH.sub.2).sub.n CO.sub.2 H, --O(CH.sub.2).sub.m CO.sub.2 H, --(CH.sub.2).sub.n O(CH.sub.2).sub.m CO.sub.2 H, --CONH(CH.sub.2).sub.m CO.sub.2 H, --CH(OZ)(CO.sub.2 H), --CH(Z)(CO.sub.2 H), --(CH.sub.2).sub.n SO.sub.3 H, --(CH.sub.2).sub.n PO.sub.3 D.sub.1 D.sub.2, --NH(CH.sub.2).sub.m CO.sub.2 H, --CONH(CHR.sub.6)CO.sub.2 H, (1-H-tetrazolyl-5-alkyl-), and --OH;R.sub.1 and R.sub.2 are independently selected from the group consisting of hydrogen, alkyl, halogen, --OZ, --NO.sub.2, --NH.sub.2 and --NHZ;R.sub.3 is selected from the group consisting of hydrogen, halogen, alkyl, --OZ and --NHZ;R.sub.4 is selected from the group consisting of hydrogen, halogen, alkyl, hydroxyl, hydroxyl-O-sulfate and --OZ;R.sub.5 is selected from the group consisting of hydroxyl, --CN, --N.sub.3, --NH.sub.2, --NHNH.sub.2, --NE.sub.1 E.sub.2, --NHE.sub.1, --NHCO(CH.sub.2).sub.n CO.sub.2 H, --S(CH.sub.2).sub.m CO.sub.2 H and --NHCHNHNH.sub.2 ;R.sub.6 is selected from the group consisting of hydrogen, alkyl, aralkyl, hydroxyalkyl, aminoalkyl, alkyl carboxylic acid and alkyl carboxamide;wherein n is 0 to 6, m is 1 to 6, p is 0 to 6, b is 0 to 2, Z is alkyl, aryl or aralkyl, D.sub.1 and D.sub.2 are independantly hydrogen or alkyl, E.sub.1 is alkyl or --(CH.sub.2).sub.8 CO.sub.2 H, and E.sub.2 is alkyl, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof. This invention also relates to methods of inhibiting the binding of E-selectin and/or P-selectin to sialyl-Lewis.sup.x or sialyl-Lewis.sup.a presented on a cell surface using said compounds and to pharmaceutically active compositions comprising compounds that inhibit the binding of E-selectin to sialyl-Lewis.sup.x and to methods of treatment of septic shock, ARDS, Crohn's disease, chronic inflammatory diseases, such as psoriasis and rheumatoid arthritis, and reperfusion injuries that occur following heart attacks, strokes and organ transplants.

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