公开(公告)号：US06331637B1

公开(公告)日：2001-12-18

申请号：US09274280

申请日：1999-03-22

申请人： Ming Fai Chan ,  Chengde Wu ,  Bore Gowda Raju ,  Timothy Kogan ,  Adam Kois ,  Erik Joel Verner ,  Rosario Silvestre Castillo ,  Venkatachalapathi Yalamoori ,  Vitukudi Narayanaiyengar Balaji

发明人： Ming Fai Chan ,  Chengde Wu ,  Bore Gowda Raju ,  Timothy Kogan ,  Adam Kois ,  Erik Joel Verner ,  Rosario Silvestre Castillo ,  Venkatachalapathi Yalamoori ,  Vitukudi Narayanaiyengar Balaji

IPC分类号： C07D26110

CPC分类号： C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

摘要： N-alkyl, N-alkenyl, N-alkynyl, N-aryl and N-fused bicyclo or tricyclo thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, (phenyl) and (phenoxy)thienylsulfonamides, (phenyl) and (phenoxy)furylsulfonamides, and (phenyl) and (phenoxy)pyrrolylsulfonamides and methods of using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

摘要翻译： 提供N-烷基，N-烯基，N-炔基，N-芳基和N-稠合双环或三环噻吩基，呋喃基和吡咯基磺酰胺以及调节或改变肽内皮素家族活性的方法。 特别地，（苯基）和（苯氧基）噻吩基磺酰胺，（苯基）和（苯氧基）呋喃基磺酰胺和（苯基）和（苯氧基）吡咯烷磺酰胺和使用这些磺酰胺抑制内皮素肽与内皮素受体结合的方法 提供了具有磺酰胺的受体。 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或其前体来治疗内皮素介导的病症的方法。

公开(公告)号：US06384261B1

公开(公告)日：2002-05-07

申请号：US09146679

申请日：1998-09-03

申请人： Ming Fai Chan ,  Erik Joel Verner

发明人： Ming Fai Chan ,  Erik Joel Verner

IPC分类号： C07C6934

CPC分类号： C07F9/247 ,  C07F9/650905 ,  C07F9/6512 ,  C07F9/653

摘要： Phosphoramidates and phosphinic amides and related compounds are provided. Also provided are methods that use the compounds for modulating the activity of the endothelin family of peptides are provided. In particular, compounds having formula: in which A, B, R1 and R2 are as described are provided. Also provided are methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these compounds or prodrugs thereof. Methods for elucidating the physiological and pathophysiological roles of endothelin, as well as isolating endothelin receptors are also provided.

摘要翻译： 提供了磷酰胺化物和次膦酰胺和相关化合物。 还提供了使用化合物调节肽的内皮素家族的活性的方法。 特别地，提供了具有下式的化合物：其中A，B，R 1和R 2如上所述。 还提供了通过施用有效量的一种或多种这些化合物或其前药来治疗内皮素介导的病症的方法。 还提供了阐明内皮素的生理和病理生理学作用以及分离内皮素受体的方法。

公开(公告)号：US06376523B1

公开(公告)日：2002-04-23

申请号：US09439802

申请日：1999-11-12

申请人： Ming Fai Chan ,  Bore Gowda Raju ,  Adam Kois ,  Erik Joel Verner ,  Chengde Wu ,  Rosario Silvestre Castillo ,  Venkatachalapathi Yalamoori ,  Vitukudi Narayanaiyengar Balaji

发明人： Ming Fai Chan ,  Bore Gowda Raju ,  Adam Kois ,  Erik Joel Verner ,  Chengde Wu ,  Rosario Silvestre Castillo ,  Venkatachalapathi Yalamoori ,  Vitukudi Narayanaiyengar Balaji

IPC分类号： A61K3142

CPC分类号： A61K31/42 ,  A61K31/47 ,  C07D261/16

摘要： N-(5-isoxazolyl)benzenesulfonamides and N-(3-isoxazolyl)benzenesulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(5-isoxazolyl)biphenylsulfonamides and N-(3-isoxazolyl)biphenylsulfonamides and methods for inhibiting the binding of an endothelin peptide to an endothelin receptor or increasing the activity of endothelin peptides by contacting the receptor with a sulfonamide are provided. N-isoxzolyl-4-biphenylsulfonamides are particularly preferred. These compounds exhibit activity as endothelin receptor B antagonists. Methods for treating endothelin-mediated disorders, particularly inflammatory diseases, such as asthma, by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

摘要翻译： 提供N-（5-异恶唑基）苯磺酰胺和N-（3-异恶唑基）苯磺酰胺以及调节或改变肽内皮素家族活性的方法。 特别地，提供N-（5-异恶唑基）联苯磺酰胺和N-（3-异恶唑基）联苯磺酰胺以及通过使受体与磺酰胺接触来抑制内皮素肽与内皮素受体结合或增加内皮素肽活性的方法 。 N-异恶唑基-4-联苯磺酰胺是特别优选的。 这些化合物表现出作为内皮素受体B拮抗剂的活性。 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或其前药来治疗内皮素介导的疾病，特别是炎性疾病如哮喘的方法。

公开(公告)号：US5962490A

公开(公告)日：1999-10-05

申请号：US721183

申请日：1996-09-27

申请人： Ming Fai Chan ,  Chengde Wu ,  Bore Gowda Raju ,  Timothy Kogan ,  Adam Kois ,  Erik Joel Verner ,  Rosario Silvestre Castillo ,  Venkatachalapathi Yalamorri ,  Vitukudi Narayanaiyengar Balaji

发明人： Ming Fai Chan ,  Chengde Wu ,  Bore Gowda Raju ,  Timothy Kogan ,  Adam Kois ,  Erik Joel Verner ,  Rosario Silvestre Castillo ,  Venkatachalapathi Yalamorri ,  Vitukudi Narayanaiyengar Balaji

IPC分类号： C07D419/12 ,  A61K31/381 ,  A61K31/42 ,  A61K31/422 ,  A61K31/423 ,  A61K31/433 ,  A61K31/496 ,  A61P1/00 ,  A61P9/00 ,  A61P9/10 ,  A61P9/12 ,  A61P11/06 ,  A61P11/08 ,  A61P13/12 ,  A61P15/00 ,  A61P27/02 ,  A61P29/00 ,  A61P43/00 ,  C07D261/10 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

CPC分类号： C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

摘要： Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)-furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides 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以及调节或改变肽内皮素家族的活性的方法。 特别地，提供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）吡咯烷基磺酰胺和使用这些磺酰胺用于通过使受体与磺酰胺接触来抑制内皮素肽与内皮素受体结合的方法 。 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或其前体来治疗内皮素介导的病症的方法。

公开(公告)号：US5958905A

公开(公告)日：1999-09-28

申请号：US624706

申请日：1996-03-26

申请人： Ming Fai Chan ,  Erik Joel Verner

发明人： Ming Fai Chan ,  Erik Joel Verner

IPC分类号： A61K31/00 ,  A61K31/66 ,  A61K31/661 ,  A61K31/6615 ,  A61K31/664 ,  A61P1/00 ,  A61P9/00 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  A61P11/06 ,  A61P11/08 ,  A61P13/12 ,  A61P15/00 ,  A61P17/02 ,  A61P27/02 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00 ,  C07F9/24 ,  C07F9/44 ,  C07F9/6509 ,  C07F9/6512 ,  C07F9/653 ,  C07F9/6539 ,  A61K31/42 ,  C07D261/14

CPC分类号： C07F9/650941 ,  C07F9/247 ,  C07F9/65127 ,  C07F9/653

摘要： Phosphoramidates and phosphinic amides and related compounds are provided. Also provided are methods that use the compounds for modulating the activity of the endothelin family of peptides are provided. In particular, compounds having formula: ##STR1## in which A, B, R.sup.1 and R.sup.2 are as described are provided. Also provided are methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these compounds or prodrugs thereof. Methods for elucidating the physiological and pathophysiological roles of endothelin, as well as isolating endothelin receptors are also provided.

摘要翻译： 提供了磷酰胺化物和次膦酰胺和相关化合物。 还提供了使用化合物调节肽的内皮素家族的活性的方法。 特别地，提供了具有下式的化合物：其中A，B，R 1和R 2如上所述。 还提供了通过施用有效量的一种或多种这些化合物或其前药来治疗内皮素介导的病症的方法。 还提供了阐明内皮素的生理和病理生理学作用以及分离内皮素受体的方法。

公开(公告)号：US06613804B2

公开(公告)日：2003-09-02

申请号：US10006256

申请日：2001-12-04

申请人： Ming Fai Chan ,  Timothy Kogan ,  Erik Joel Verner ,  Adam Kois ,  Vitukudi Narayanaiyengar Balaji

发明人： Ming Fai Chan ,  Timothy Kogan ,  Erik Joel Verner ,  Adam Kois ,  Vitukudi Narayanaiyengar Balaji

IPC分类号： A61K3118

CPC分类号： C07D413/14 ,  C07D261/14 ,  C07D261/16 ,  C07D413/12

摘要： Biphenylsulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, bicyclic or tricyclic carbon or heterocyclic ring biphenylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

公开(公告)号：US06342610B2

公开(公告)日：2002-01-29

申请号：US08913331

申请日：1997-11-07

申请人： Ming Fai Chan ,  Chengde Wu ,  Bore Gowda Raju ,  Timothy Kogan ,  Erik Joel Verner ,  Rosario Silvestre Castillo ,  Venkatachalapathi Yalamoori ,  Adam Kois ,  Vitukudi Narayanaiyengar Balaji

发明人： Ming Fai Chan ,  Chengde Wu ,  Bore Gowda Raju ,  Timothy Kogan ,  Erik Joel Verner ,  Rosario Silvestre Castillo ,  Venkatachalapathi Yalamoori ,  Adam Kois ,  Vitukudi Narayanaiyengar Balaji

IPC分类号： C07D20736

CPC分类号： C07D413/12 ,  C07D261/14 ,  C07D261/16 ,  C07D261/20 ,  C07D413/14 ,  C07D417/12

摘要： Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides 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以及调节或改变肽内皮素家族的活性的方法。 特别地，提供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，以及使用这些磺酰胺用于通过使受体与磺酰胺接触来抑制内皮素肽与内皮素受体结合的方法。 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或其前体来治疗内皮素介导的病症的方法。

公开(公告)号：US06541498B2

公开(公告)日：2003-04-01

申请号：US09749716

申请日：2000-12-27

申请人： Ming Fai Chan ,  Bore Gowda Raju ,  Adam Kois ,  Erik Joel Verner ,  Chengde Wu ,  Rosario Silvestre Castillo ,  Venkatachalapathi Yalamoori ,  Vitukudi Narayanaiyengar Balaji ,  Kalyanaraman Ramnarayan

发明人： Ming Fai Chan ,  Bore Gowda Raju ,  Adam Kois ,  Erik Joel Verner ,  Chengde Wu ,  Rosario Silvestre Castillo ,  Venkatachalapathi Yalamoori ,  Vitukudi Narayanaiyengar Balaji ,  Kalyanaraman Ramnarayan

IPC分类号： A61K3142

CPC分类号： A61K31/42 ,  A61K31/47 ,  C07D261/16

摘要： N-(5-isoxazolyl)benzenesulfonamides and N-(3-isoxazolyl)benzenesulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(5-isoxazolyl)biphenylsulfonamides and N-(3-isoxazolyl)biphenylsulfonamides and methods for inhibiting the binding of an endothelin peptide to an endothelin receptor or increasing the activity of endothelin peptides by contacting the receptor with a sulfonamide are provided. N-isoxzolyl-4-biphenylsulfonamides are particularly preferred. These compounds exhibit activity as endothelin receptor B antagonists. Methods for treating endothelin-mediated disorders, particularly inflammatory diseases, such as asthma, by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

公开(公告)号：US6030991A

公开(公告)日：2000-02-29

申请号：US730633

申请日：1996-12-06

申请人： Ming Fai Chan ,  Bore Gowda Raju ,  Adam Kois ,  Erik Joel Verner ,  Chengde Wu ,  Rosario Silvestre Castillo ,  Venkatachalapathi Yalamoori ,  Vitukudi Narayanaiyengar Balaji

发明人： Ming Fai Chan ,  Bore Gowda Raju ,  Adam Kois ,  Erik Joel Verner ,  Chengde Wu ,  Rosario Silvestre Castillo ,  Venkatachalapathi Yalamoori ,  Vitukudi Narayanaiyengar Balaji

IPC分类号： A61K31/42 ,  C07D261/10

CPC分类号： A61K31/42 ,  C07D261/10

摘要： N-(5-isoxazolyl)benzenesulfonamides and N-(3-isoxazolyl) benzene-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(5-isoxazolyl)-biphenylsulfonamides and N-(3-isoxazolyl)biphenylsulfonamides and methods for inhibiting the binding of an endothelin peptide to an endothelin receptor or increasing the activity of endothelin peptides by contacting the receptor with a sulfonamide are provided. N-isoxzolyl-4-biphenylsulfonamides are particularly preferred. These compounds exhibit activity as endothelin receptor B antagonists. Methods for treating endothelin-mediated disorders, particularly inflammatory diseases, such as asthma, by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

摘要翻译： 提供N-（5-异恶唑基）苯磺酰胺和N-（3-异恶唑基）苯磺酰胺以及调节或改变肽内皮素家族活性的方法。 特别地，N-（5-异恶唑基） - 联苯磺酰胺和N-（3-异恶唑基）联苯磺酰胺和通过使受体与磺酰胺接触来抑制内皮素肽与内皮素受体的结合或增加内皮素肽的活性的方法是 提供。 N-异恶唑基-4-联苯磺酰胺是特别优选的。 这些化合物表现出作为内皮素受体B拮抗剂的活性。 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或其前药来治疗内皮素介导的疾病，特别是炎性疾病如哮喘的方法。

公开(公告)号：US06265428B1

公开(公告)日：2001-07-24

申请号：US09327661

申请日：1999-06-08

申请人： Ming Fai Chan ,  Vitukudi Narayanaiyengar Balaji ,  Rosario Silvestre Castillo ,  Adam Kois ,  Bore Gowda Raju ,  Chengde Wu

发明人： Ming Fai Chan ,  Vitukudi Narayanaiyengar Balaji ,  Rosario Silvestre Castillo ,  Adam Kois ,  Bore Gowda Raju ,  Chengde Wu

IPC分类号： A61K314164

CPC分类号： A61K31/506 ,  A61K31/192 ,  A61K31/36 ,  A61K31/505 ,  C07D239/60 ,  C07D317/64 ,  C07D405/14 ,  Y10S206/828

摘要： Methods, compositions, and compounds for modulating the activity of an endothelin peptide are provided. The methods use compositions that contain compounds of formula (1): where X and Y are selected from groups that include O, S, and NH; and Ar1, Ar2 and Ar3 are independently selected from substituted or unsubstituted groups that include 5 to 6 membered aryl groups and heteroaryl groups that contain one or two heteroatom(s). The methods are effected by contacting endothelin receptors with one or more of the compounds or with compositions containing one or more of the compounds prior to, simultaneously with, or subsequent to contacting the receptors with an endothelin peptide.

摘要翻译： 提供了调节内皮素肽活性的方法，组合物和化合物。 该方法使用含有式（1）化合物的组合物：其中X和Y选自包括O，S和NH的基团; 并且Ar 1，Ar 2和Ar 3独立地选自包含5至6元芳基的取代或未取代的基团和含有一个或两个杂原子的杂芳基。 所述方法通过使内皮素受体与一种或多种化合物或含有一种或多种化合物的组合物在使受体与内皮素肽接触之前，同时或之后接触来实现。