公开(公告)号：WO2005042521A3

公开(公告)日：2005-07-07

申请号：PCT/US2004036666

申请日：2004-11-03

Applicant: PHARMACIA CORP ,  BROWN DAVID L ,  GRAPPERHAUS MARGARET L ,  KASSAB DARREN J ,  MASSA MARK A ,  MCDONALD JOSEPH J ,  MULLINS PATRICK B ,  RICO JOSEPH G ,  SCHMIDT MICHELLE A

Inventor： BROWN DAVID L ,  GRAPPERHAUS MARGARET L ,  KASSAB DARREN J ,  MASSA MARK A ,  MCDONALD JOSEPH J ,  MULLINS PATRICK B ,  RICO JOSEPH G ,  SCHMIDT MICHELLE A

IPC: A61K31/452 ,  C07D211/16 ,  C07D211/22 ,  C07D211/66 ,  C07D211/96 ,  C07D309/08 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  A61K31/44

CPC classification number: C07D401/14 ,  C07D211/66 ,  C07D211/96 ,  C07D309/08 ,  C07D401/06 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14

Abstract: This invention is directed generally to proteinase (also known as "protease") inhibitors, and, more particularly, to piperidinyl- and piperazinyl-sulfonylmethyl hydroxamic acids that, inter alia, inhibit matrix metalloproteinase (also known as "matrix metalloprotease" or "MMP") activity and/or aggrecanase activity. Such hydroxamic acids generally correspond in structure to formula (I); (wherein A , A , Y, E , E , E , and R are as defined in this specification), and further include salts of such compounds. This invention also is directed to compositions of such hydroxamic acids, intermediates for the syntheses of such hydroxamic acids, methods for making such hydroxamic acids, and methods for treating conditions (particularly pathological conditions) associated with MMP activity and/or aggrecanase activity.

Abstract translation: 本发明一般涉及蛋白酶（也称为“蛋白酶”）抑制剂，尤其涉及哌啶基和哌嗪基 - 磺酰基甲基异羟肟酸，其特别是抑制基质金属蛋白酶（也称为“基质金属蛋白酶”或“MMP “）活性和/或蛋白聚糖蛋白聚糖酶活性。 这种异羟肟酸通常在结构上对应于式（I）; （其中A 1，A 2，Y，E 1，E 2，E 3和R x如本说明书中所定义），并且还包括这些化合物的盐。 本发明还涉及这种异羟肟酸的组合物，用于合成这种异羟肟酸的中间体，制备这种异羟肟酸的方法，以及用于治疗与MMP活性和/或蛋白聚糖蛋白聚糖酶活性相关的病症（特别是病理状态）的方法。

公开(公告)号：WO2004000811A1

公开(公告)日：2003-12-31

申请号：PCT/US2003/020028

申请日：2003-06-25

Applicant: PHARMACIA CORPORATION ,  CHEN, Yiyuan ,  FRESKOS, John, N. ,  GASIECKI, Alan, F. ,  GRAPPERHAUS, Margaret, L. ,  HANSEN, Donald, W., Jr. ,  HEINTZ, Robert, M. ,  KHANNA, Ish, K. ,  KOLODZIEJ, Steve, A. ,  MANTEGANI, Sergio ,  MASSA, Mark, A. ,  MCDONALD, Joseph, J. ,  MISCHKE, Deborah, A. ,  NAGY, Mark, A. ,  PERRONE, Ettore ,  SCHMIDT, Michelle, A. ,  SPANGLER, Dale, P. ,  TALLEY, John, J. ,  TRIVEDI, Mahima ,  WYNN, Thomas, A. ,  BECKER, Daniel, P. ,  RICO, Joseph, G.

Inventor： CHEN, Yiyuan ,  FRESKOS, John, N. ,  GASIECKI, Alan, F. ,  GRAPPERHAUS, Margaret, L. ,  HANSEN, Donald, W., Jr. ,  HEINTZ, Robert, M. ,  KHANNA, Ish, K. ,  KOLODZIEJ, Steve, A. ,  MANTEGANI, Sergio ,  MASSA, Mark, A. ,  MCDONALD, Joseph, J. ,  MISCHKE, Deborah, A. ,  NAGY, Mark, A. ,  PERRONE, Ettore ,  SCHMIDT, Michelle, A. ,  SPANGLER, Dale, P. ,  TALLEY, John, J. ,  TRIVEDI, Mahima ,  WYNN, Thomas, A. ,  BECKER, Daniel, P. ,  RICO, Joseph, G.

IPC: C07D213/34

CPC classification number: C07D241/12 ,  C07C317/46 ,  C07D211/66 ,  C07D213/34 ,  C07D309/08 ,  C07D335/02 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: This invention is directed generally to hydroxamic acid and amide compounds (including salts of such compounds), and, more particularly, to aryl- and heteroaryl-­arylsulfonylmethyl hydroxamic acids and amides that, inter alia , inhibit protease activity, particularly matrix metalloproteinase (also known as "matrix metalloprotease" or "MMP") activity and/or aggrecanase activity. These compounds generally correspond in structure to formula (I): wherein A l , A 2 , A 3 , E l , E 2 , E 3 , and E 4 are as defined in this patent. This invention also is directed to compositions of such compounds, intermediates for the syntheses of such compounds, methods for making such compounds, and methods for treating conditions associated with MMP activity and/or aggrecanase activity, particularly pathological conditions.

Abstract translation: 本发明一般涉及异羟肟酸和酰胺化合物（包括这些化合物的盐），更具体地说，涉及芳基 - 和杂芳基 - 芳基磺酰基甲基异羟肟酸和酰胺，其特别是抑制蛋白酶活性，特别是基质金属蛋白酶 作为“基质金属蛋白酶”或“MMP”）活性和/或蛋白聚糖蛋白聚糖酶活性。 这些化合物通常在结构上对应于式（I）：其中A 1，A 2，A 3，E 11，E 2，E 3和E 4如 在该专利中定义。 本发明还涉及这些化合物的组合物，用于合成这些化合物的中间体，制备这些化合物的方法，以及用于治疗与MMP活性和/或蛋白聚糖蛋白聚糖酶活性特别是病理状况相关的病症的方法。

公开(公告)号：WO2009016498A1

公开(公告)日：2009-02-05

申请号：PCT/IB2008/002046

申请日：2008-07-29

Applicant: PFIZER INC. ,  SCHNUTE, Mark, E. ,  CARROLL, Jeffery, Neal ,  HANAU, Cathleen, Elizabeth ,  MCREYNOLDS, Matthew, David ,  SCHOLTEN, Jeffrey, Allen ,  MCDONALD, Joseph, J. ,  GRAPPERHAUS, Margaret, L. ,  MASSA, Mark, Alan ,  RUMINSKI, Peter, G. ,  SCHMIDT, Michelle, Ann ,  STROHBACK, Joseph, Walter ,  HAMPER, Bruce, Cameron ,  FLETCHER, Theresa, R. ,  ROGERS, Michael, David ,  O'BRIEN, Patrick, Michael ,  NAHRA, Joe ,  MORRIS, Mark, Anthony ,  ROARK, William, Howard

Inventor： SCHNUTE, Mark, E. ,  CARROLL, Jeffery, Neal ,  HANAU, Cathleen, Elizabeth ,  MCREYNOLDS, Matthew, David ,  SCHOLTEN, Jeffrey, Allen ,  MCDONALD, Joseph, J. ,  GRAPPERHAUS, Margaret, L. ,  MASSA, Mark, Alan ,  RUMINSKI, Peter, G. ,  SCHMIDT, Michelle, Ann ,  STROHBACK, Joseph, Walter ,  HAMPER, Bruce, Cameron ,  FLETCHER, Theresa, R. ,  ROGERS, Michael, David ,  O'BRIEN, Patrick, Michael ,  NAHRA, Joe ,  MORRIS, Mark, Anthony ,  ROARK, William, Howard

IPC: C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D405/04 ,  C07D405/14 ,  C07D413/14 ,  A61K31/44 ,  A61K31/506 ,  A61P19/00 ,  A61P35/00

CPC classification number: C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D405/04 ,  C07D405/14 ,  C07D413/14

Abstract: The prsent invention relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof, processes for the preparation of, intermediates used in the preparation of, and compositions containing such compounds and the uses of such compounds as anti-inflammatory agents.

Abstract translation: 本发明涉及式（I）的化合物及其药学上可接受的盐，制备用途的中间体，含有这些化合物的组合物和这些化合物作为抗炎剂的用途。

公开(公告)号：WO2005042521A2

公开(公告)日：2005-05-12

申请号：PCT/US2004/036666

申请日：2004-11-03

Applicant: PHARMACIA CORPORATION ,  BROWN, David, L. ,  GRAPPERHAUS, Margaret, L. ,  KASSAB, Darren, J. ,  MASSA, Mark, A. ,  MCDONALD, Joseph, J. ,  MULLINS, Patrick, B. ,  RICO, Joseph, G. ,  SCHMIDT, Michelle, A.

Inventor： BROWN, David, L. ,  GRAPPERHAUS, Margaret, L. ,  KASSAB, Darren, J. ,  MASSA, Mark, A. ,  MCDONALD, Joseph, J. ,  MULLINS, Patrick, B. ,  RICO, Joseph, G. ,  SCHMIDT, Michelle, A.

IPC: C07D405/00

CPC classification number: C07D401/14 ,  C07D211/66 ,  C07D211/96 ,  C07D309/08 ,  C07D401/06 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14

Abstract: This invention is directed generally to proteinase (also known as “protease”) inhibitors, and, more particularly, to piperidinyl- and piperazinyl-sulfonylmethyl hydroxamic acids that, inter alia , inhibit matrix metalloproteinase (also known as “matrix metalloprotease” or “MMP”) activity and/or aggrecanase activity. Such hydroxamic acids generally correspond in structure to formula (I); (wherein A 1 , A 2 , Y, E 1 , E 2 , E 3 , and R x are as defined in this specification), and further include salts of such compounds. This invention also is directed to compositions of such hydroxamic acids, intermediates for the syntheses of such hydroxamic acids, methods for making such hydroxamic acids, and methods for treating conditions (particularly pathological conditions) associated with MMP activity and/or aggrecanase activity.

Abstract translation: 本发明通常涉及蛋白酶（也称为“蛋白酶”）抑制剂，并且更具体地涉及哌啶基 - 和哌嗪基 - 磺酰基甲基异羟肟酸，其中尤其是， 抑制基质金属蛋白酶（也称为“基质金属蛋白酶”或“MMP”）活性和/或聚集蛋白聚糖酶活性。 这样的异羟肟酸通常在结构上对应于式（I）; （其中A 1，A 2，Y，E 1，E 2，E 3，E 3，E 3， 和R x如本说明书中所定义），并且还包括这些化合物的盐。 本发明还涉及这样的异羟肟酸的组合物，用于合成这种异羟肟酸的中间体，制备这种异羟肟酸的方法以及用于治疗与MMP活性和/或聚集蛋白聚糖酶活性相关的病症（特别是病理状态）的方法。 p>

公开(公告)号：WO2009016498A8

公开(公告)日：2010-11-11

申请号：PCT/IB2008002046

申请日：2008-07-29

Applicant: PFIZER ,  SCHNUTE MARK E ,  CARROLL JEFFERY NEAL ,  HANAU CATHLEEN ELIZABETH ,  MCREYNOLDS MATTHEW DAVID ,  SCHOLTEN JEFFREY ALLEN ,  MCDONALD JOSEPH J ,  GRAPPERHAUS MARGARET L ,  MASSA MARK ALAN ,  RUMINSKI PETER G ,  SCHMIDT MICHELLE ANN ,  STROHBACH JOSEPH WALTER ,  HAMPER BRUCE CAMERON ,  FLETCHER THERESA R ,  ROGERS MICHAEL DAVID ,  O'BRIEN PATRICK MICHAEL ,  NAHRA JOE ,  MORRIS MARK ANTHONY ,  ROARK WILLIAM HOWARD

Inventor： SCHNUTE MARK E ,  CARROLL JEFFERY NEAL ,  HANAU CATHLEEN ELIZABETH ,  MCREYNOLDS MATTHEW DAVID ,  SCHOLTEN JEFFREY ALLEN ,  MCDONALD JOSEPH J ,  GRAPPERHAUS MARGARET L ,  MASSA MARK ALAN ,  RUMINSKI PETER G ,  SCHMIDT MICHELLE ANN ,  STROHBACH JOSEPH WALTER ,  HAMPER BRUCE CAMERON ,  FLETCHER THERESA R ,  ROGERS MICHAEL DAVID ,  O'BRIEN PATRICK MICHAEL ,  NAHRA JOE ,  MORRIS MARK ANTHONY ,  ROARK WILLIAM HOWARD

IPC: C07D401/04 ,  A61K31/44 ,  A61K31/506 ,  A61P19/00 ,  A61P35/00 ,  C07D401/14 ,  C07D403/04 ,  C07D405/04 ,  C07D405/14 ,  C07D413/14

CPC classification number: C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D405/04 ,  C07D405/14 ,  C07D413/14

Abstract: The prsent invention relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof, processes for the preparation of, intermediates used in the preparation of, and compositions containing such compounds and the uses of such compounds as anti-inflammatory agents.

Abstract translation: 本发明涉及式（I）的化合物及其药学上可接受的盐，制备用途的中间体，含有这些化合物的组合物，以及这些化合物作为抗炎剂的用途。

公开(公告)号：WO2004048368A3

公开(公告)日：2004-08-12

申请号：PCT/US0337942

申请日：2003-11-24

Applicant: PHARMACIA CORP ,  BECKER DANIEL P ,  CARROLL JEFFERY N ,  FOBIAN YVETTE M ,  GRAPPERHAUS MARGARET L ,  HANSEN DONALD W JR ,  HEINTZ ROBERT M ,  KASSAB DARREN J ,  MASSA MARK A ,  MCDONALD JOSEPH J ,  NAGY MARK A ,  PITZELE BARNETT S ,  RICO JOSEPH G ,  SCHMIDT MICHELLE A ,  SPANGLER DALE P

Inventor： BECKER DANIEL P ,  CARROLL JEFFERY N ,  FOBIAN YVETTE M ,  GRAPPERHAUS MARGARET L ,  HANSEN DONALD W JR ,  HEINTZ ROBERT M ,  KASSAB DARREN J ,  MASSA MARK A ,  MCDONALD JOSEPH J ,  NAGY MARK A ,  PITZELE BARNETT S ,  RICO JOSEPH G ,  SCHMIDT MICHELLE A ,  SPANGLER DALE P

IPC: A61P9/10 ,  A61P19/00 ,  A61P35/00 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D417/12 ,  C07D417/14 ,  C07D513/04 ,  A61K31/41 ,  A61K31/425 ,  A61K31/435

CPC classification number: C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D417/12 ,  C07D417/14 ,  C07D513/04

Abstract: This invention is directed generally to heteroarylsulfonylmethyl hydroxamic acids and amides that, inter alia, tend to inhibit protease activity, particularly matrix metalloproteinase (also known as "matrix metalloprotease" or "MMP") activity and/or aggrecanase activity. This invention also is directed to compositions of such compounds; intermediates for the syntheses of such compounds; methods for making such compounds; and methods for treating conditions associated with MMP, tumor necrosis factors (or "TNFs"), and/or aggrecanase activity, particularly pathological conditions.

Abstract translation: 本发明通常涉及杂芳基磺酰基甲基异羟肟酸和酰胺，其特别是倾向于抑制蛋白酶活性，特别是基质金属蛋白酶（也称为“基质金属蛋白酶”或“MMP”）活性和/或软骨聚集蛋白聚糖酶活性。 本发明还涉及这些化合物的组合物; 用于合成这些化合物的中间体; 制备这些化合物的方法; 以及用于治疗与MMP相关的病症，肿瘤坏死因子（或“TNFs”）和/或软骨聚集蛋白聚糖酶活性，特别是病理状况的方法。

公开(公告)号：WO2004048368A2

公开(公告)日：2004-06-10

申请号：PCT/US2003/037942

申请日：2003-11-24

Applicant: PHARMACIA CORPORATION ,  BECKER, Daniel, P. ,  CARROLL, Jeffery, N. ,  FOBIAN, Yvette, M. ,  GRAPPERHAUS, Margaret, L. ,  HANSEN, Donald, W., Jr. ,  HEINTZ, Robert, M. ,  KASSAB, Darren, J. ,  MASSA, Mark, A. ,  MCDONALD, Joseph, J. ,  NAGY, Mark, A. ,  PITZELE, Barnett, S. ,  RICO, Joseph, G. ,  SCHMIDT, Michelle, A. ,  SPANGLER, Dale, P.

Inventor： BECKER, Daniel, P. ,  CARROLL, Jeffery, N. ,  FOBIAN, Yvette, M. ,  GRAPPERHAUS, Margaret, L. ,  HANSEN, Donald, W., Jr. ,  HEINTZ, Robert, M. ,  KASSAB, Darren, J. ,  MASSA, Mark, A. ,  MCDONALD, Joseph, J. ,  NAGY, Mark, A. ,  PITZELE, Barnett, S. ,  RICO, Joseph, G. ,  SCHMIDT, Michelle, A. ,  SPANGLER, Dale, P.

IPC: C07D409/00

CPC classification number: C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D417/12 ,  C07D417/14 ,  C07D513/04

Abstract: This invention is directed generally to heteroarylsulfonylmethyl hydroxamic acids and amides that, inter alia, tend to inhibit protease activity, particularly matrix metalloproteinase (also known as "matrix metalloprotease" or "MMP") activity and/or aggrecanase activity. This invention also is directed to compositions of such compounds; intermediates for the syntheses of such compounds; methods for making such compounds; and methods for treating conditions associated with MMP, tumor necrosis factors (or "TNFs"), and/or aggrecanase activity, particularly pathological conditions.

Abstract translation: 本发明通常涉及杂芳基磺酰基甲基异羟肟酸和酰胺，其特别倾向于抑制蛋白酶活性，特别是基质金属蛋白酶（也称为“基质金属蛋白酶”或 “MMP”）活性和/或聚集蛋白聚糖酶活性。 本发明还涉及这些化合物的组合物; 用于合成这些化合物的中间体; 制造这种化合物的方法; 和治疗与MMP，肿瘤坏死因子（或“TNF”）和/或聚集蛋白聚糖酶活性，特别是病理学病症有关的病症的方法。

公开(公告)号：WO0119823A9

公开(公告)日：2002-09-26

申请号：PCT/US0025154

申请日：2000-09-14

Applicant: MONSANTO CO ,  RILEY DENNIS ,  NEUMANN WILLIAM L ,  HENKE SUSAN L ,  LENNON PATRICK ,  ASTON KARL W ,  SALVEMINI DANIELA ,  SIKORSKI JAMES A ,  FOBIAN YVETTE ,  GRAPPERHAUS MARGARET L ,  KUSTURIN CARRIE L

Inventor： RILEY DENNIS ,  NEUMANN WILLIAM L ,  HENKE SUSAN L ,  LENNON PATRICK ,  ASTON KARL W ,  SALVEMINI DANIELA ,  SIKORSKI JAMES A ,  FOBIAN YVETTE ,  GRAPPERHAUS MARGARET L ,  KUSTURIN CARRIE L

IPC: A61K31/555 ,  A61P1/00 ,  A61P1/04 ,  A61P7/02 ,  A61P9/02 ,  A61P9/10 ,  A61P9/12 ,  A61P17/06 ,  A61P19/02 ,  A61P25/04 ,  A61P25/36 ,  A61P29/00 ,  A61P35/00 ,  A61P35/04 ,  A61P37/06 ,  A61P39/00 ,  A61P39/06 ,  B01J31/22 ,  C07D471/00 ,  C07D471/06 ,  C07D471/08 ,  C07F13/00

CPC classification number: C07D471/06 ,  A61K31/555 ,  C07D471/08 ,  C07F13/005

Abstract: The present invention relates to compounds which are effective as catalysts for dismutating superoxide and, more particularly, the manganese or iron complexes of substituted, unsaturated heterocyclic pentaazacyclopentadecane ligands which catalytically dismutate superoxide.

Abstract translation: 本发明涉及有效作为用于分解超氧化物的催化剂的化合物，更具体地说，涉及催化分解超氧化物的取代的，不饱和杂环五氮杂环十五烷配体的锰或铁络合物。