公开(公告)号：US5238935A

公开(公告)日：1993-08-24

申请号：US839522

申请日：1992-02-20

Applicant: Sundeep Dugar ,  Timothy Kogan

Inventor： Sundeep Dugar ,  Timothy Kogan

IPC: C07D217/06 ,  C07D217/14 ,  C07D217/18 ,  C07D217/20

CPC classification number: C07D217/18 ,  C07D217/06 ,  C07D217/14 ,  C07D217/20

Abstract: N-acyltetrahydroisoquinolines including novel compounds of the formula ##STR1## wherein R.sup.1 is a C10-C25 alkyl chain; a substituted C10-C25 alkyl chain; an interrupted C10-C25 alkyl chain; a substituted interrupted C10-C25 alkyl chain; diphenylamino; di-(R.sup.2 -substituted phenyl)amino; di-(heteroaryl)amino; di-(R.sup.2 -substituted heteroaryl)amino; diphenylmethyl; or di-(R.sup.2 -substituted phenyl)methyl;R.sup.2 is hydroxy, lower alkyl, lower alkoxy, halogeno, amino, lower alkylamino or di-(lower alkyl)amino;R.sup.3, R.sup.4 and R.sup.5 are independently H or --(CH.sub.2).sub.n --Ar;Ar is phenyl, R.sup.2 -substituted phenyl, heteroaryl or R.sup.2 - substituted heteroaryl;n=0,1 or 2;m=0,1 or 2;or a pharmaceutically acceptable salt thereof, useful in the treatment of atherosclerosis are disclosed.

Abstract translation: N-酰基四氢异喹啉，包括新的式（Ⅰ）化合物，其中R1是C10-C25烷基链; 取代的C 10 -C 25烷基链; 中断的C10-C25烷基链; 取代的中断C10-C25烷基链; 二苯胺 二（R 2取代的苯基）氨基; 二（杂芳基）氨基; 二（R2-取代的杂芳基）氨基; 二苯基甲基; 或二（R 2取代的苯基）甲基; R2是羟基，低级烷基，低级烷氧基，卤代，氨基，低级烷基氨基或二（低级烷基）氨基; R3，R4和R5独立地为H或 - （CH2）n-Ar; Ar是苯基，R 2取代的苯基，杂芳基或R 2取代的杂芳基; n = 0,1或2; m = 0,1或2; 或其药学上可接受的盐，其可用于治疗动脉粥样硬化。

公开(公告)号：US5326762A

公开(公告)日：1994-07-05

申请号：US885420

申请日：1992-05-19

Applicant: John Clader ,  Sundeep Dugar ,  Timothy Kogan ,  Bradley Tait ,  Wayne Vaccaro

Inventor： John Clader ,  Sundeep Dugar ,  Timothy Kogan ,  Bradley Tait ,  Wayne Vaccaro

IPC: C07C233/18 ,  C07C233/20 ,  C07C233/22 ,  C07C233/36 ,  C07C233/38 ,  C07C233/40 ,  C07C233/49 ,  C07C233/51 ,  C07C235/50 ,  C07C237/22 ,  C07C271/22 ,  C07C311/08 ,  H01N43/40 ,  C07D211/70

CPC classification number: C07C233/20 ,  C07C233/18 ,  C07C233/22 ,  C07C233/36 ,  C07C233/38 ,  C07C233/40 ,  C07C233/49 ,  C07C233/51 ,  C07C235/50 ,  C07C237/22 ,  C07C271/22 ,  C07C311/08 ,  Y10S514/824

Abstract: Amides of the formula ##STR1## wherein R.sub.1 and R.sub.2 are independently heteroaryl, X-substituted heteroaryl, X-substituted phenyl, N-substituted triazinyl or N-substituted imidazolyl;and in addition, one of R.sub.1 and R.sub.2 can be as defined above and the other can be phenyl;R.sub.3 is an alkyl chain of 2 to 25 carbon atoms, saturated or unsaturated; an alkyl chain as defined substituted by one or more substituents selected from the group consisting of phenyl, X-substituted phenyl, heteroaryl and X-substituted heteroaryl; an alkyl chain as defined interrupted by one or more groups independently selected from the group consisting of --O--, --S--, --SO--, --SO.sub.2 --, --NH--, --N(lower alkyl)--, --C(O)--, phenylene, X-substituted phenylene, heteroarylene and X-substituted heteroarylene; or an interrupted alkyl chain as defined substituted by one or more substituents selected form the group consisting of phenyl, X-substituted phenyl, heteroaryl and X-substituted heteroaryl;R.sub.4 is hydrogen, lower alkyl, phenyl, X-substituted phenyl, heteroaryl or X-substituted heteroaryl; or a pharmaceutically acceptable salt thereof, useful as inhibitors of acyl-coenzyme A:cholesterol acyl transferase and therefore in the treatment of atherosclerosis are disclosed.

Abstract translation: 其中R 1和R 2独立地是杂芳基，X取代的杂芳基，X取代的苯基，N-取代的三嗪基或N-取代的咪唑基; 此外，R 1和R 2中的一个可以如上所定义，另一个可以是苯基; R3是2至25个碳原子的饱和或不饱和的烷基链; 由一个或多个选自苯基，X取代的苯基，杂芳基和X取代的杂芳基的取代基取代的烷基链; 由一个或多个独立地选自-O - ， - S - ， - SO - ， - SO 2 - ， - NH - ， - N（低级烷基） - ， - C ） - ，亚苯基，X取代亚苯基，亚杂芳基和X取代亚杂芳基; 或被一个或多个选自苯基，X取代的苯基，杂芳基和X取代的杂芳基的取代基取代的中断的烷基链; R4是氢，低级烷基，苯基，X取代的苯基，杂芳基或X取代的杂芳基; 或其药学上可接受的盐，其可用作酰基辅酶A的抑制剂：胆固醇酰基转移酶，因此用于治疗动脉粥样硬化。

公开(公告)号：US5124337A

公开(公告)日：1992-06-23

申请号：US702993

申请日：1991-05-20

Applicant: Sundeep Dugar ,  Timothy Kogan

Inventor： Sundeep Dugar ,  Timothy Kogan

IPC: A61K31/47 ,  A61K31/472 ,  A61P3/06 ,  A61P9/10 ,  C07D217/06 ,  C07D217/14 ,  C07D217/18 ,  C07D217/20

CPC classification number: C07D217/20 ,  C07D217/06 ,  C07D217/14 ,  C07D217/18

Abstract: N-acyltetrahydroisoquinolines including novel compounds of the formula ##STR1## wherein R.sup.1 is a C10-C25 alkyl chain; a substituted C10-C25 alkyl chain; an interrupted C10-C25 alkyl chain; a substituted interrupted C10-C25 alkyl chain; diphenylamino; di-(R.sup.2 -substituted phenyl)amino; di-(heteroaryl)amino; di-R.sup.2 -substituted heteroary)amino; diphenylmethyl; or di-(R.sup.2 -substituted phenyl)methyl;R.sup.2 is hydroxy, lower alkyl, lower alkoxy, halogeno, amino, lower alkylamino or di-(lower alkyl)amino;R.sup.3, R.sup.4 and R.sup.5 are independently H or --(CH.sub.2 .sub.n --Ar;Ar is phenyl, R.sup.2 -substituted phenyl, heteroaryl or R.sup.2 -substituted heteroaryl;n=0,1 or 2;m=0,1 or 2;or a pharmaceutically acceptable salt thereof, useful in the treatment of atherosclerosis are disclosed.

公开(公告)号：US5149709A

公开(公告)日：1992-09-22

申请号：US547644

申请日：1990-07-03

Applicant: John Clader ,  Sundeep Dugar ,  Timothy Kogan ,  Bradley Tait ,  Wayne Vaccaro

Inventor： John Clader ,  Sundeep Dugar ,  Timothy Kogan ,  Bradley Tait ,  Wayne Vaccaro

IPC: C07C233/18 ,  C07C233/20 ,  C07C233/22 ,  C07C233/36 ,  C07C233/38 ,  C07C233/40 ,  C07C233/49 ,  C07C233/51 ,  C07C235/50 ,  C07C237/22 ,  C07C271/22 ,  C07C311/08

CPC classification number: C07C233/20 ,  C07C233/18 ,  C07C233/22 ,  C07C233/36 ,  C07C233/38 ,  C07C233/40 ,  C07C233/49 ,  C07C233/51 ,  C07C235/50 ,  C07C237/22 ,  C07C271/22 ,  C07C311/08 ,  Y10S514/824

Abstract: Amides of the formula ##STR1## wherein R.sub.1 and R.sub.2 are independently heteroaryl, X-substituted heteroaryl, X-substituted phenyl, N-substituted triazinyl or N-substituted imidazolyl;and in addition, one of R.sub.1 and R.sub.2 can be as defined above and the other can be phenyl;R.sub.3 is an alkyl chain of 2 to 25 carbon atoms, saturated or unsaturated; an alkyl chain as defined substituted by one or more substituents selected from the group consisting of phenyl, X-substituted phenyl, heteroaryl and X-substituted heteroaryl; an alkyl chain as defined interrupted by one or more groups independently selected from the group consisting of --O--, --S--, --SO--, --SO.sub.2 --, --NH--, --N(lower alkyl)--, --C(O)--, phenylene, X-substituted phenylene, heteroarylene and X-substituted heteroarylene; or an interrupted alkyl chain as defined substituted by one or more substituents selected from the group consisting of phenyl, X-substituted phenyl, heteroaryl and X-substituted heteroaryl;R.sub.4 is hydrogen, lower alkyl, phenyl, X-substituted phenyl, heteroaryl or X-substituted heteroaryl; or a pharmaceutically acceptable salt thereof, useful as inhibitors of acyl-coenzyme A:cholesterol acyl transferase and therefore in the treatment of atherosclerosis are disclosed.

Abstract translation: 其中R 1和R 2独立地是杂芳基，X取代的杂芳基，X取代的苯基，N-取代的三嗪基或N-取代的咪唑基; 此外，R 1和R 2中的一个可以如上所定义，另一个可以是苯基; R3是2至25个碳原子的饱和或不饱和的烷基链; 由一个或多个选自苯基，X取代的苯基，杂芳基和X取代的杂芳基的取代基取代的烷基链; 由一个或多个独立地选自-O - ， - S - ， - SO - ， - SO 2 - ， - NH - ， - N（低级烷基） - ， - C ） - ，亚苯基，X取代亚苯基，亚杂芳基和X取代亚杂芳基; 或被一个或多个选自苯基，X取代的苯基，杂芳基和X取代的杂芳基的取代基取代的间断的烷基链; R4是氢，低级烷基，苯基，X取代的苯基，杂芳基或X取代的杂芳基; 或其药学上可接受的盐，其可用作酰基辅酶A的抑制剂：胆固醇酰基转移酶，因此用于治疗动脉粥样硬化。

公开(公告)号：US5962490A

公开(公告)日：1999-10-05

申请号：US721183

申请日：1996-09-27

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

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

IPC: 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 classification number: C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: 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.

Abstract translation: 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：US06420567B1

公开(公告)日：2002-07-16

申请号：US08938325

申请日：1997-09-26

Applicant: Chengde Wu ,  Bore Gowda Raju ,  Timothy Kogan ,  Natalie Blok

Inventor： Chengde Wu ,  Bore Gowda Raju ,  Timothy Kogan ,  Natalie Blok

IPC: C07D26104

CPC classification number: C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: Thienyl-, furyl- and pyrrolyl-sulfonamides, formulations of pharmaceutically-acceptable salts thereof 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, formulations thereof 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 the activity of endothelin are also provided.

Abstract translation: 提供噻吩基，呋喃基和吡咯基磺酰胺，其药学上可接受的盐的制剂和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，其制剂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 被提供。 还提供了通过施用有效量的一种或多种这些抑制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：US4766109A

公开(公告)日：1988-08-23

申请号：US919950

申请日：1986-10-17

Applicant: Michael F. Czarniecki ,  Laura L. Verbiar ,  Timothy Kogan

Inventor： Michael F. Czarniecki ,  Laura L. Verbiar ,  Timothy Kogan

IPC: A61K38/00 ,  C07K7/06 ,  A61K37/02

CPC classification number: C07K7/06 ,  A61K38/00

Abstract: Hydrophobic peptides having antihypertensive activity are disclosed. Also disclosed are pharmaceutical compositions comprising a hydrophobic peptide and a method of treatment of mammalian hypertension comprising administering a hydrophobic peptide to a hypertensive mammal.

Abstract translation: 公开了具有抗高血压活性的疏水肽。 还公开了包含疏水肽和治疗哺乳动物高血压的方法的药物组合物，包括向高血压哺乳动物施用疏水性肽。

公开(公告)号：US06632829B2

公开(公告)日：2003-10-14

申请号：US10011610

申请日：2001-11-05

Applicant: Chengde Wu ,  Bore Gowda Raju ,  Timothy Kogan ,  Natalie Blok ,  Patricia Woodard

Inventor： Chengde Wu ,  Bore Gowda Raju ,  Timothy Kogan ,  Natalie Blok ,  Patricia Woodard

IPC: A61K3142

CPC classification number: C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: Thienyl-, furyl- and pyrrolyl-sulfonamides, formulations of pharmaceutically-acceptable salts thereof 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, formulations thereof 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 the activity of endothelin are also provided.

Abstract translation: 提供噻吩基，呋喃基和吡咯基磺酰胺，其药学上可接受的盐的制剂和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，其制剂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 被提供。 还提供了通过施用有效量的一种或多种这些抑制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：US06432994B1

公开(公告)日：2002-08-13

申请号：US09403599

申请日：2000-03-27

Applicant: Chengde Wu ,  Natalie Blok ,  Timothy Kogan ,  Karin Keller ,  Patricia Woodard

Inventor： Chengde Wu ,  Natalie Blok ,  Timothy Kogan ,  Karin Keller ,  Patricia Woodard

IPC: A61K3142

CPC classification number: C07D413/14 ,  C07D261/16 ,  C07D409/12 ,  C07D413/12 ,  C07D417/14

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US06331637B1

公开(公告)日：2001-12-18

申请号：US09274280

申请日：1999-03-22

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

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

IPC: C07D26110

CPC classification number: C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: 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.

Abstract translation: 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。