公开(公告)号：US06583299B1

公开(公告)日：2003-06-24

申请号：US09572019

申请日：2000-05-16

申请人： Susan L Hockerman ,  Daniel P. Becker ,  Louis J Bedell ,  Gary A DeCrescenzo ,  John N Freskos ,  Daniel P Getman ,  Robert M Heintz ,  Madeleine H Li ,  Brent V Mischke ,  Clara I Villamil ,  Thomas E Barta

发明人： Susan L Hockerman ,  Daniel P. Becker ,  Louis J Bedell ,  Gary A DeCrescenzo ,  John N Freskos ,  Daniel P Getman ,  Robert M Heintz ,  Madeleine H Li ,  Brent V Mischke ,  Clara I Villamil ,  Thomas E Barta

IPC分类号： C07D31500

CPC分类号： C07K5/06026 ,  A61K38/00 ,  C07C317/48 ,  C07C317/50 ,  C07C323/65 ,  C07D307/58

摘要： A family of molecules is disclosed that inhibit matrix metalloprotease (MMP) activity, and particularly inhibit the activity of one or more of MMP-2, MMP-9, or MMP-13, while generally exhibiting little activity against MMP-1. A contemplated compound also exhibits little inhibition of the production of TNF. A contemplated compound is an &agr;-amino-&bgr;-sulfonyl carbocyclo, heterocyclo, aryl, or heteroaryl hydroxamic acid. Also disclosed are processes for preparing a contemplated compound and for treating a mammal having a condition associated with pathological matrix metalloprotease activity.

摘要翻译： 公开了分子家族抑制基质金属蛋白酶（MMP）活性，特别是抑制MMP-2，MMP-9或MMP-13中的一种或多种的活性，而通常对MMP-1几乎没有活性。 预期的化合物也对TNF的产生几乎没有抑制作用。 预期的化合物是α-氨基-β-磺酰基碳环，杂环基，芳基或杂芳基异羟肟酸。 还公开了制备预期化合物和用于治疗具有与病理基质金属蛋白酶活性相关的病症的哺乳动物的方法。

公开(公告)号：US06750228B1

公开(公告)日：2004-06-15

申请号：US09570731

申请日：2000-05-12

申请人： Thomas E Barta ,  Daniel P Becker ,  Louis J Bedell ,  Terri L Boehm ,  Jeffrey N Carroll ,  Gary A DeCrescenzo ,  Yvette M Fobian ,  John N Freskos ,  Daniel P Getman ,  Joseph J McDonald ,  Madeleine H Li ,  Susan L Hockerman ,  Susan C Howard ,  Steve A Kolodziej ,  Deborah A Mischke ,  Joseph G Rico ,  Nathan W Stehle ,  Michael B Tollefson ,  William F Vernier ,  Clara I Villamil

发明人： Thomas E Barta ,  Daniel P Becker ,  Louis J Bedell ,  Terri L Boehm ,  Jeffrey N Carroll ,  Gary A DeCrescenzo ,  Yvette M Fobian ,  John N Freskos ,  Daniel P Getman ,  Joseph J McDonald ,  Madeleine H Li ,  Susan L Hockerman ,  Susan C Howard ,  Steve A Kolodziej ,  Deborah A Mischke ,  Joseph G Rico ,  Nathan W Stehle ,  Michael B Tollefson ,  William F Vernier ,  Clara I Villamil

IPC分类号： A61K31445

CPC分类号： C07D231/12 ,  C07D211/66 ,  C07D233/56 ,  C07D249/08 ,  C07D309/08 ,  C07D335/02 ,  C07D401/06 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12

摘要： A treatment process is disclosed that comprises administering an effective amount of an aromatic sulfone hydroxamic acid that exhibits excellent inhibitory activity of one or more matrix metalloprotease (MMP) enzymes, such as MMP-2, MMP-9 and MMP-13, while exhibiting substantially less inhibition at least of MMP-1 to a host having a condition associated with pathological matrix metalloprotease activity. Also disclosed are metalloprotease inhibitor compounds having those selective activities, processes for manufacture of such compounds and pharmaceutical compositions using an inhibitor. A contemplated compound corresponds in structure to formula B, below,

公开(公告)号：US07115632B1

公开(公告)日：2006-10-03

申请号：US09569034

申请日：2000-05-11

申请人： Louis J Bedell ,  Joseph J McDonald ,  Thomas E Barta ,  Daniel P Becker ,  Rao N Shashidhar ,  John N Freskos ,  Brent V Mischke ,  Daniel P Getman ,  Gary A DeCrescenzo ,  Clara I Villamil

发明人： Louis J Bedell ,  Joseph J McDonald ,  Thomas E Barta ,  Daniel P Becker ,  Rao N Shashidhar ,  John N Freskos ,  Brent V Mischke ,  Daniel P Getman ,  Gary A DeCrescenzo ,  Clara I Villamil

IPC分类号： A61K31/445 ,  C07D401/12

CPC分类号： C07C311/16 ,  C07C311/21 ,  C07C317/44 ,  C07D207/48 ,  C07D211/96 ,  C07D295/26

摘要： A sulfonyl aromatic or heteroaromatic ring hydroxamic acid compound that inter alia inhibits matrix metalloprotease activity is disclosed as are a treatment process that comprises administering a contemplated sulfonyl aromatic or heteroaromatic ring hydroxamic acid compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity. A contemplated compound corresponds in structure to the formula wherein W and the R groups are defined elsewhere.

摘要翻译： 公开了包括抑制基质金属蛋白酶活性的磺酰芳族或杂芳族环异羟肟酸化合物，其处理方法包括将具有MMP酶抑制有效量的考虑的磺酰芳族或杂芳族环异羟肟酸化合物施用于具有条件 与病理基质金属蛋白酶活性相关。 考虑的化合物在结构上对应于下式，其中W和R基团在其他地方定义。

公开(公告)号：US06696449B2

公开(公告)日：2004-02-24

申请号：US09909227

申请日：2001-07-19

申请人： Thomas E. Barta ,  Daniel P. Becker ,  Louis J. Bedell ,  Gary A. DeCrescenzo ,  John N Freskos ,  Daniel P. Getman ,  Joseph J. McDonald ,  Brent V. Mischke ,  Shashidhar N. Rao ,  Clara I. Villamil

发明人： Thomas E. Barta ,  Daniel P. Becker ,  Louis J. Bedell ,  Gary A. DeCrescenzo ,  John N Freskos ,  Daniel P. Getman ,  Joseph J. McDonald ,  Brent V. Mischke ,  Shashidhar N. Rao ,  Clara I. Villamil

IPC分类号： A61K31496

CPC分类号： C07D295/26 ,  C07C311/16 ,  C07C311/21 ,  C07C317/22 ,  C07C317/44 ,  C07C323/65 ,  C07D207/14 ,  C07D207/16 ,  C07D207/48 ,  C07D211/16 ,  C07D211/18 ,  C07D211/46 ,  C07D211/54 ,  C07D211/62 ,  C07D211/96 ,  C07D213/30 ,  C07D213/82 ,  C07D295/15 ,  C07D309/12 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12

摘要： This invention is directed to sulfonyl aromatic hydroxamic acid compounds and salts thereof that, inter alia, inhibit matrix metalloprotease (MMP) activity and/or aggrecanase activity. In some particularly preferred embodiments, the compound corresponds in structure to one of the following formulas: wherein W2, the R groups, and —A—R—E—Y are described in more detail in Applicants' specification. This invention also is directed to a process that comprises administering such a compound or pharmaceutically acceptable salt thereof to a host animal having a condition associated with MMP activity.

摘要翻译： 本发明涉及磺酰芳族异羟肟酸化合物及其盐，其特别是抑制基质金属蛋白酶（MMP）活性和/或蛋白聚糖蛋白聚糖酶活性。 在一些特别优选的实施方案中，该化合物在结构上对应于下式之一：其中W 2，R基团和-A-R-E-Y在申请人的说明书中有更详细的描述。 本发明还涉及一种方法，其包括将这种化合物或其药学上可接受的盐施用于具有与MMP活性相关的病症的宿主动物。

公开(公告)号：US06214861B1

公开(公告)日：2001-04-10

申请号：US09501265

申请日：2000-02-09

申请人： Daniel P Getman ,  Gary A DeCrescenzo ,  John N Freskos ,  Michael L Vazquez ,  James A Sikorski ,  Balekudru Devadas ,  Srinivasan Nagarajan ,  David L Brown ,  Joseph J McDonald

发明人： Daniel P Getman ,  Gary A DeCrescenzo ,  John N Freskos ,  Michael L Vazquez ,  James A Sikorski ,  Balekudru Devadas ,  Srinivasan Nagarajan ,  David L Brown ,  Joseph J McDonald

IPC分类号： A61K314025

CPC分类号： C07K5/06165 ,  A61K38/00 ,  C07K5/06139

摘要： Selected heterocycle carbonyl amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, composition and method for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.

摘要翻译： 选择的杂环羰基氨基酸羟乙基氨基磺酰胺化合物作为逆转录病毒蛋白酶抑制剂是有效的，特别是作为HIV蛋白酶抑制剂。 本发明涉及这种逆转录病毒蛋白酶抑制剂，更具体地涉及所选择的新化合物，用于抑制逆转录病毒蛋白酶如人类免疫缺陷病毒（HIV）蛋白酶的组合物和方法，预防性地预防逆转录病毒感染或逆转录病毒的扩散，以及 治疗逆转录病毒感染。

公开(公告)号：US06407134B1

公开(公告)日：2002-06-18

申请号：US09775682

申请日：2001-02-05

申请人： Daniel P Getman ,  Gary A DeCrescenzo ,  John N Freskos ,  Michael L Vazquez ,  James A Sikorski ,  Balekudru Devadas ,  Srinivasan Nagarajan ,  David L Brown ,  Joseph J McDonald

发明人： Daniel P Getman ,  Gary A DeCrescenzo ,  John N Freskos ,  Michael L Vazquez ,  James A Sikorski ,  Balekudru Devadas ,  Srinivasan Nagarajan ,  David L Brown ,  Joseph J McDonald

IPC分类号： A61K314025

CPC分类号： C07K5/021 ,  A61K38/00 ,  C07K5/06139 ,  C07K5/06165

摘要： Selected heterocyclecarbonyl amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, composition and method for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.

摘要翻译： 选择的杂环羰基氨基酸羟乙基氨基磺酰胺化合物作为逆转录病毒蛋白酶抑制剂是有效的，特别是作为HIV蛋白酶的抑制剂。 本发明涉及这种逆转录病毒蛋白酶抑制剂，更具体地涉及所选择的新化合物，用于抑制逆转录病毒蛋白酶如人类免疫缺陷病毒（HIV）蛋白酶的组合物和方法，预防性地预防逆转录病毒感染或逆转录病毒的扩散，以及 治疗逆转录病毒感染。

公开(公告)号：US6063795A

公开(公告)日：2000-05-16

申请号：US307711

申请日：1999-05-10

申请人： Daniel P Getman ,  Gary A DeCrescenzo ,  John N Freskos ,  Michael L Vazquez ,  James A Sikorski ,  Balekudru Devadas ,  Srinivasan Nagarajan ,  David L Brown ,  Joseph J McDonald

发明人： Daniel P Getman ,  Gary A DeCrescenzo ,  John N Freskos ,  Michael L Vazquez ,  James A Sikorski ,  Balekudru Devadas ,  Srinivasan Nagarajan ,  David L Brown ,  Joseph J McDonald

IPC分类号： A61K38/55 ,  A61K31/18 ,  A61K38/00 ,  A61P3/00 ,  A61P31/12 ,  A61P31/18 ,  C07D215/48 ,  C07K5/062 ,  C07K5/078 ,  A61K31/445 ,  C07D405/12

CPC分类号： C07K5/06165 ,  C07K5/06139 ,  A61K38/00

摘要： Selected heterocyclecarbonyl amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, composition and method for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.

公开(公告)号：US07339078B2

公开(公告)日：2008-03-04

申请号：US11501926

申请日：2006-08-10

申请人： Daniel P Getman ,  Gary A DeCrescenzo ,  John N Freskos ,  Michael L Vazquez ,  James A Sikorski ,  Balekudru Devadas ,  Srinivasan Raj Nagarajan ,  David L Brown ,  Joseph J McDonald

发明人： Daniel P Getman ,  Gary A DeCrescenzo ,  John N Freskos ,  Michael L Vazquez ,  James A Sikorski ,  Balekudru Devadas ,  Srinivasan Raj Nagarajan ,  David L Brown ,  Joseph J McDonald

IPC分类号： C07C311/03 ,  C07C311/16 ,  A61K31/18 ,  A61K31/36 ,  C07D317/44

CPC分类号： C07K5/06026 ,  A61K31/16 ,  A61K31/165 ,  A61K31/357 ,  A61K31/36 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/428 ,  A61K38/00 ,  C07K5/06078 ,  C07K5/06139 ,  C07K5/06191

摘要： Selected bis-amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, compositions, and methods for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.

摘要翻译： 选择的双氨基酸羟乙基氨基磺酰胺化合物作为逆转录病毒蛋白酶抑制剂是有效的，特别是作为HIV蛋白酶的抑制剂。 本发明涉及这样的逆转录病毒蛋白酶抑制剂，更具体地涉及用于抑制逆转录病毒蛋白酶（例如人免疫缺陷病毒（HIV）蛋白酶），预防性逆转录病毒感染或逆转录病毒扩散的选择的新化合物，组合物和方法， 并治疗逆转录病毒感染。

公开(公告)号：US06673822B2

公开(公告)日：2004-01-06

申请号：US10120791

申请日：2002-04-12

申请人： Daniel P Getman ,  Gary A DeCrescenzo ,  John N Freskos ,  Michael L Vazquez ,  James A Sikorski ,  Balekudru Devadas ,  Srinivasan Nagarajan ,  David L Brown ,  Joseph J McDonald

发明人： Daniel P Getman ,  Gary A DeCrescenzo ,  John N Freskos ,  Michael L Vazquez ,  James A Sikorski ,  Balekudru Devadas ,  Srinivasan Nagarajan ,  David L Brown ,  Joseph J McDonald

IPC分类号： A61K31428

CPC分类号： C07K5/021 ,  A61K38/00 ,  C07K5/06139 ,  C07K5/06165

摘要： Selected heterocyclecarbonyl amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, composition and method for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.

公开(公告)号：US06388132B1

公开(公告)日：2002-05-14

申请号：US09694783

申请日：2000-10-24

申请人： Daniel P Getman ,  Gary A DeCrescenzo ,  John N Freskos ,  Michael L Vazquez ,  James A Sikorski ,  Balekudru Devadas ,  Srinivasan Raj Nagarajan ,  David L Brown ,  Joseph J McDonald

发明人： Daniel P Getman ,  Gary A DeCrescenzo ,  John N Freskos ,  Michael L Vazquez ,  James A Sikorski ,  Balekudru Devadas ,  Srinivasan Raj Nagarajan ,  David L Brown ,  Joseph J McDonald

IPC分类号： C07C31103

CPC分类号： C07K5/06026 ,  A61K38/00 ,  A61K39/00 ,  C07K14/20 ,  C07K16/1207

摘要： Selected bis-amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, composition and method for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.

摘要翻译： 选择的双氨基酸羟乙基氨基磺酰胺化合物作为逆转录病毒蛋白酶抑制剂是有效的，特别是作为HIV蛋白酶的抑制剂。 本发明涉及这种逆转录病毒蛋白酶抑制剂，更具体地涉及所选择的新化合物，用于抑制逆转录病毒蛋白酶如人类免疫缺陷病毒（HIV）蛋白酶的组合物和方法，预防性地预防逆转录病毒感染或逆转录病毒的扩散，以及 治疗逆转录病毒感染。