公开(公告)号：US06436989B1

公开(公告)日：2002-08-20

申请号：US08998050

申请日：1997-12-24

申请人： Michael R. Hale ,  Roger D. Tung ,  Christopher T. Baker ,  Andrew Spaltenstein

发明人： Michael R. Hale ,  Roger D. Tung ,  Christopher T. Baker ,  Andrew Spaltenstein

IPC分类号： A61K31665

CPC分类号： C07D405/12 ,  C07C311/18 ,  C07D307/20 ,  C07F9/65515 ,  C07F9/65844 ,  C07H15/04

摘要： The present invention relates to prodrugs of a class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of prodrugs of HIV aspartyl protease inhibitors characterized by favorable aqueous solubility, high oral bioavailability and facile in vivo generation of the active ingredient. This invention also relates to pharmaceutical compositions comprising these prodrugs. The prodrugs and pharmaceutical compositions of this invention are particularly well suited for decreasing the pill burden and increasing patient compliance. This invention also relates to methods of treating mammals with these prodrugs and pharmaceutical compositions.

摘要翻译： 本发明涉及作为天冬氨酰蛋白酶抑制剂的一类磺酰胺的前药。 在一个实施方案中，本发明涉及HIV天冬氨酰蛋白酶抑制剂的新一类前药，其特征在于有利的水溶性，高口服生物利用度和活性成分的体内易生成。 本发明还涉及包含这些前药的药物组合物。 本发明的前药和药物组合物特别适用于降低药丸负担并增加患者依从性。 本发明还涉及用这些前药和药物组合物治疗哺乳动物的方法。

公开(公告)号：US07919523B2

公开(公告)日：2011-04-05

申请号：US12217517

申请日：2008-07-02

申请人： Michael R. Hale ,  Christopher T. Baker ,  Timothy A. Stammers ,  Ronald George Sherrill ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Francois Maltais ,  Clarence Webster Andrews, III ,  John Franklin Miller ,  Vicente Samano

发明人： Michael R. Hale ,  Christopher T. Baker ,  Timothy A. Stammers ,  Ronald George Sherrill ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Francois Maltais ,  Clarence Webster Andrews, III ,  John Franklin Miller ,  Vicente Samano

IPC分类号： A61K31/357 ,  C07D319/06

CPC分类号： C07C311/19 ,  C07C311/29 ,  C07C311/42 ,  C07C311/46 ,  C07C317/18 ,  C07D307/20 ,  C07D319/06 ,  C07D493/04 ,  C07F9/6561

摘要： The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

摘要翻译： 本发明涉及一类新型的磺酰胺，它们是天冬氨酰蛋白酶抑制剂。 在一个实施方案中，本发明涉及以特定结构和物理化学特征为特征的新型HIV天冬氨酰蛋白酶抑制剂。 本发明还涉及包含这些化合物的药物组合物。 本发明的化合物和药物组合物特别适用于抑制HIV-1和HIV-2蛋白酶活性，因此可有利地用作针对HIV-1和HIV-2病毒的抗病毒剂。 本发明还涉及使用本发明化合物抑制HIV天冬氨酰蛋白酶活性的方法和用于筛选抗HIV活性化合物的方法。

公开(公告)号：US06319946B1

公开(公告)日：2001-11-20

申请号：US09500781

申请日：2000-02-09

申请人： Michael R. Hale ,  Christopher T. Baker ,  Timothy A. Stammers ,  Ronald George Sherrill ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Francois Maltais ,  Clarence Webster Andrews, III ,  John Franklin Miller ,  Vicente Samano

发明人： Michael R. Hale ,  Christopher T. Baker ,  Timothy A. Stammers ,  Ronald George Sherrill ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Francois Maltais ,  Clarence Webster Andrews, III ,  John Franklin Miller ,  Vicente Samano

IPC分类号： A61K31357

CPC分类号： C07C311/19 ,  C07C311/29 ,  C07C311/42 ,  C07C311/46 ,  C07C317/18 ,  C07D307/20 ,  C07D319/06 ,  C07D493/04 ,  C07F9/6561

摘要： The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

摘要翻译： 本发明涉及一类新型的磺酰胺，它们是天冬氨酰蛋白酶抑制剂。 在一个实施方案中，本发明涉及以特定结构和物理化学特征为特征的新型HIV天冬氨酰蛋白酶抑制剂。 本发明还涉及包含这些化合物的药物组合物。 本发明的化合物和药物组合物特别适用于抑制HIV-1和HIV-2蛋白酶活性，因此可有利地用作针对HIV-1和HIV-2病毒的抗病毒剂。 本发明还涉及使用本发明化合物抑制HIV天冬氨酰蛋白酶活性的方法和用于筛选抗HIV活性化合物的方法。

公开(公告)号：US20090042973A1

公开(公告)日：2009-02-12

申请号：US12217517

申请日：2008-07-02

申请人： Michael R. Hale ,  Christopher T. Baker ,  Timothy A. Stammers ,  Ronald George Sherrill ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Francois Maltais ,  Clarence Webster Andrews, III ,  John Franklin Miller ,  Vicente Samano

发明人： Michael R. Hale ,  Christopher T. Baker ,  Timothy A. Stammers ,  Ronald George Sherrill ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Francois Maltais ,  Clarence Webster Andrews, III ,  John Franklin Miller ,  Vicente Samano

IPC分类号： A61K31/343 ,  C07C255/03 ,  C07D307/78 ,  A61K31/352 ,  A61P31/18 ,  C07D319/16 ,  A61K31/277

CPC分类号： C07C311/19 ,  C07C311/29 ,  C07C311/42 ,  C07C311/46 ,  C07C317/18 ,  C07D307/20 ,  C07D319/06 ,  C07D493/04 ,  C07F9/6561

摘要： The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

公开(公告)号：US06617350B2

公开(公告)日：2003-09-09

申请号：US09927271

申请日：2001-08-09

申请人： Michael R. Hale ,  Christopher T. Baker ,  Timothy A. Stammers ,  Ronald George Sherrill ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  François Maltais ,  Clarence Webster Andrews, III ,  John Franklin Miller ,  Vicente Samano

发明人： Michael R. Hale ,  Christopher T. Baker ,  Timothy A. Stammers ,  Ronald George Sherrill ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  François Maltais ,  Clarence Webster Andrews, III ,  John Franklin Miller ,  Vicente Samano

IPC分类号： A61K3134

CPC分类号： C07C311/19 ,  C07C311/29 ,  C07C311/42 ,  C07C311/46 ,  C07C317/18 ,  C07D307/20 ,  C07D319/06 ,  C07D493/04 ,  C07F9/6561

摘要： The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

公开(公告)号：US20090274650A1

公开(公告)日：2009-11-05

申请号：US12370175

申请日：2009-02-12

申请人： Michael R. Hale ,  Roger Tung ,  Stephen Price ,  Robin David Wilkes ,  Wayne Carl Schairer ,  Ashley Nicholas Jarvis ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Vicente Samano ,  Istvan Kaldor ,  John Franklin Miller ,  Michael Stephen Brieger ,  Ronald George Sherrill

发明人： Michael R. Hale ,  Roger Tung ,  Stephen Price ,  Robin David Wilkes ,  Wayne Carl Schairer ,  Ashley Nicholas Jarvis ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Vicente Samano ,  Istvan Kaldor ,  John Franklin Miller ,  Michael Stephen Brieger ,  Ronald George Sherrill

IPC分类号： A61K31/443 ,  C07D493/04 ,  C07D413/12 ,  C07D317/46 ,  A61K31/5377 ,  A61K31/357 ,  A61K31/34 ,  A61K31/52 ,  A61K31/522 ,  A61K31/496 ,  A61K31/427 ,  A61K31/472 ,  A61K31/513 ,  A61K31/708 ,  A61K38/21 ,  A61K38/20 ,  A61P31/12 ,  A61P31/18

CPC分类号： C07D493/04 ,  A61K31/352 ,  A61K31/36 ,  A61K45/06 ,  C07D317/46 ,  A61K2300/00

摘要： The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

摘要翻译： 本发明涉及一类新型的磺酰胺，它们是天冬氨酰蛋白酶抑制剂。 在一个实施方案中，本发明涉及以特定结构和物理化学特征为特征的新型HIV天冬氨酰蛋白酶抑制剂。 本发明还涉及包含这些化合物的药物组合物。 本发明的化合物和药物组合物特别适用于抑制HIV-1和HIV-2蛋白酶活性，因此可有利地用作针对HIV-1和HIV-2病毒的抗病毒剂。 本发明还涉及使用本发明化合物抑制HIV天冬氨酰蛋白酶活性的方法和用于筛选抗HIV活性化合物的方法。

公开(公告)号：US08455497B2

公开(公告)日：2013-06-04

申请号：US12370175

申请日：2009-02-12

申请人： Michael R. Hale ,  Roger Tung ,  Stephen Price ,  Robin David Wilkes ,  Wayne Carl Schairer ,  Ashley Nicholas Jarvis ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Vicente Samano ,  Istvan Kaldor ,  John Franklin Miller ,  Michael Stephen Brieger ,  Ronald George Sherrill

发明人： Michael R. Hale ,  Roger Tung ,  Stephen Price ,  Robin David Wilkes ,  Wayne Carl Schairer ,  Ashley Nicholas Jarvis ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Vicente Samano ,  Istvan Kaldor ,  John Franklin Miller ,  Michael Stephen Brieger ,  Ronald George Sherrill

IPC分类号： C07D493/04 ,  A61K31/34 ,  A61K31/357 ,  A61K31/36 ,  A61P31/18 ,  C07C311/16 ,  C07C311/29

CPC分类号： C07D493/04 ,  A61K31/352 ,  A61K31/36 ,  A61K45/06 ,  C07D317/46 ,  A61K2300/00

摘要： The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

公开(公告)号：US06878728B1

公开(公告)日：2005-04-12

申请号：US09591464

申请日：2000-06-09

申请人： Michael R. Hale ,  Roger Tung ,  Stephen Price ,  Robin David Wilkes ,  Wayne Carl Schairer ,  Ashley Nicholas Jarvis ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Vicente Samano ,  Istvan Kaldor ,  John Franklin Miller ,  Michael Stephen Brieger

发明人： Michael R. Hale ,  Roger Tung ,  Stephen Price ,  Robin David Wilkes ,  Wayne Carl Schairer ,  Ashley Nicholas Jarvis ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Vicente Samano ,  Istvan Kaldor ,  John Franklin Miller ,  Michael Stephen Brieger

IPC分类号： A61K31/352 ,  A61K31/36 ,  A61K45/06 ,  A61K31/454 ,  A61K31/422 ,  C07D413/14 ,  C07D417/12

CPC分类号： C07D493/04 ,  A61K31/352 ,  A61K31/36 ,  A61K45/06 ,  C07D277/24 ,  C07D317/62 ,  C07D407/12 ,  A61K2300/00

摘要： The invention provides novel compounds of formula (I) wherein all variables are as defined in the specification, that are useful as inhibitors of aspartyl proteases.

摘要翻译： 本发明提供新的式（I）化合物，其中所有变量如说明书中所定义，可用作天冬氨酰蛋白酶抑制剂。

公开(公告)号：US07304071B2

公开(公告)日：2007-12-04

申请号：US10639784

申请日：2003-08-12

申请人： John Cochran ,  Jeremy Green ,  Michael R. Hale ,  Brian Ledford ,  Francois Maltais ,  Suganthini Nanthakumar

发明人： John Cochran ,  Jeremy Green ,  Michael R. Hale ,  Brian Ledford ,  Francois Maltais ,  Suganthini Nanthakumar

IPC分类号： C07D239/42 ,  A61K31/505

CPC分类号： C07D213/74 ,  C07D239/42 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12

摘要： Described herein are compounds that are useful as protein kinase inhibitors having the formulae I and V: or a pharmaceutically acceptable salt thereof, wherein Ring B, Z1, Z2, U, T, m, n, p, Q, Q′, R1, R2, Rx, R3, and R6 are as defined herein. These compounds, and pharmaceutically acceptable compositions thereof, are useful for treating or lessening the severity of a variety of disorders, including stroke, inflammatory disorders, autoimmune diseases such as SLE lupus and psoriasis, proliferative disorders such as cancer, and conditions associated with organ transplantation.

摘要翻译： 本文描述了可用作具有式I和V的蛋白激酶抑制剂的化合物：

公开(公告)号：US07456190B2

公开(公告)日：2008-11-25

申请号：US10798766

申请日：2004-03-11

申请人： Francois Maltais ,  Alex Aronov ,  Michael R. Hale ,  Young-Choon Moon

发明人： Francois Maltais ,  Alex Aronov ,  Michael R. Hale ,  Young-Choon Moon

IPC分类号： A61K31/506 ,  A61K31/4439 ,  A61K31/401 ,  C07D403/04 ,  C07D401/14 ,  C07D207/34

CPC分类号： C07D405/04 ,  C07D207/34 ,  C07D403/04

摘要： The present invention relates to compounds useful of inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

摘要翻译： 本发明涉及可用于蛋白激酶抑制剂的化合物。 本发明还提供包含所述化合物的药学上可接受的组合物和使用该组合物治疗各种疾病，病症或病症的方法。