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：WO1995006030A1

公开(公告)日：1995-03-02

申请号：PCT/US1994009139

申请日：1994-08-23

Applicant: G.D. SEARLE & CO. ,  THE MONSANTO COMPANY ,  VAZQUEZ, Michael, L. ,  MUELLER, Richard, A. ,  TALLEY, John, J. ,  GETMAN, Daniel, P. ,  DECRESCENZO, Gary, A. ,  FRESKOS, John, N. ,  BERTENSHAW, Deborah, E. ,  HEINTZ, Robert, M.

Inventor： G.D. SEARLE & CO. ,  THE MONSANTO COMPANY

IPC: C07C311/29

CPC classification number: C07D213/30 ,  A61K38/00 ,  C07C311/05 ,  C07C311/18 ,  C07C311/29 ,  C07C311/41 ,  C07C317/10 ,  C07C317/14 ,  C07C323/67 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2601/18 ,  C07C2602/10 ,  C07D213/64 ,  C07D213/73 ,  C07D213/81 ,  C07D213/89 ,  C07D215/48 ,  C07D233/64 ,  C07D239/26 ,  C07D277/24 ,  C07D277/82 ,  C07D307/20 ,  C07D307/42 ,  C07D307/79 ,  C07D317/62 ,  C07D333/34 ,  C07D405/12 ,  C07D417/12 ,  C07K5/06026 ,  C07K5/06139

Abstract: Hydroxyethylamino sulphonamide compounds of formulae (1) and (2), wherein A, R , R , R , R , x, P and P are as defined in claims 1 and 8 are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.

Abstract translation: 式（1）和（2）的羟乙基氨基磺酰胺化合物，其中A，R 2，R 3，R 4，R 6，x，P 1和P 2定义如上 在权利要求1和8中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。

公开(公告)号：WO1994014793A1

公开(公告)日：1994-07-07

申请号：PCT/US1993011713

申请日：1993-12-08

Applicant: G. D. SEARLE & CO. ,  THE MONSANTO COMPANY ,  BERTENSHAW, Deborah, E. ,  GETMAN, Daniel ,  HEINTZ, Robert, M. ,  TALLEY, John, J. ,  REED, Kathryn, L. ,  CHRUSCHIEL, Robert, Alan ,  CLARE, Michael

Inventor： G. D. SEARLE & CO. ,  THE MONSANTO COMPANY

IPC: C07D335/02

CPC classification number: C07D333/48 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D279/12 ,  C07D335/02 ,  C07D409/12

Abstract: The present invention relates to cyclic sulfone moiety-containing hydroxyethylamine protease inhibitor compounds and pharmaceutical or method of use therefor, particularly as an inhibitor of HIV protease.

Abstract translation: 本发明涉及含环状砜部分的羟乙基胺蛋白酶抑制剂化合物及其用途的药物或方法，特别是作为HIV蛋白酶的抑制剂。

公开(公告)号：WO1993023368A1

公开(公告)日：1993-11-25

申请号：PCT/US1993004806

申请日：1993-05-20

Applicant: G.D. SEARLE & CO. ,  THE MONSANTO COMPANY ,  TALLEY, John, J. ,  GETMAN, Daniel, P. ,  DECRESCENZO, Gary, A. ,  LIN, Ko-Chung ,  VAZQUEZ, Michael, L. ,  MUELLER, Richard, A. ,  REED, Kathryn, L. ,  HEINTZ, Robert, M. ,  CLARE, Michael ,  FRESKOS, John, N. ,  SUN, Eric, T.

Inventor： G.D. SEARLE & CO. ,  THE MONSANTO COMPANY

IPC: C07C275/24

CPC classification number: C07K5/0207 ,  C07B2200/07 ,  C07C213/00 ,  C07C213/02 ,  C07C213/08 ,  C07C275/22 ,  C07C275/24 ,  C07C317/44 ,  C07D215/48 ,  C07D303/36 ,  Y02P20/55 ,  C07C215/08 ,  C07C215/28

Abstract: Compounds represented by formula (I) or a pharmaceutically acceptable salt, prodrug or ester thereof, wherein A represents radicals represented by formulae (A1, A2, A3) (values for the variables given herein), are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.

Abstract translation: 由式（I）表示的化合物或其药学上可接受的盐，前药或酯，其中A表示由式（A1，A2，A3）表示的基团（本文给出的变量的值）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。

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：WO2003091247A3

公开(公告)日：2003-11-06

申请号：PCT/US2003/013123

申请日：2003-04-25

Applicant: PHARMACIA CORPORATION ,  BARTA, Thomas, E. ,  BECKER, Daniel, P. ,  BEDELL, Louis, J. ,  BOEHM, Terri, L. ,  BROWN, David, L. ,  CARROLL, Jeffery, N. ,  CHEN, Yiyuan ,  FOBIAN, Yvette ,  FRESKOS, John, N. ,  GASIECKI, Alan, F. ,  GRAPPERHAUS, Margaret ,  HEINTZ, Robert, M. ,  HOCKERMAN, Susan, L. ,  KASSAB, Darren, J. ,  KHANNA, Ish, Kumar ,  KOLODZIEJ, Stephen, A. ,  MASSA, Mark ,  MCDONALD, Joseph ,  MISCHKE, Brent, V. ,  MISCHKE, Deborah, A. ,  MULLINS, Patrick, B. ,  NAGY, Mark ,  NORTON, Monica, B. ,  RICO, Joseph, G. ,  SCHMIDT, Michelle, A. ,  STEHLE, Nathan, W. ,  TALLEY, John, J. ,  VERNIER, William, F. ,  VILLAMILL, Clara, I. ,  WANG, Lijuan, Jane ,  WYNN, Thomas, A.

Inventor： BARTA, Thomas, E. ,  BECKER, Daniel, P. ,  BEDELL, Louis, J. ,  BOEHM, Terri, L. ,  BROWN, David, L. ,  CARROLL, Jeffery, N. ,  CHEN, Yiyuan ,  FOBIAN, Yvette ,  FRESKOS, John, N. ,  GASIECKI, Alan, F. ,  GRAPPERHAUS, Margaret ,  HEINTZ, Robert, M. ,  HOCKERMAN, Susan, L. ,  KASSAB, Darren, J. ,  KHANNA, Ish, Kumar ,  KOLODZIEJ, Stephen, A. ,  MASSA, Mark ,  MCDONALD, Joseph ,  MISCHKE, Brent, V. ,  MISCHKE, Deborah, A. ,  MULLINS, Patrick, B. ,  NAGY, Mark ,  NORTON, Monica, B. ,  RICO, Joseph, G. ,  SCHMIDT, Michelle, A. ,  STEHLE, Nathan, W. ,  TALLEY, John, J. ,  VERNIER, William, F. ,  VILLAMILL, Clara, I. ,  WANG, Lijuan, Jane ,  WYNN, Thomas, A.

IPC: C07D407/12

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.

公开(公告)号：WO1995014653A1

公开(公告)日：1995-06-01

申请号：PCT/US1994012201

申请日：1994-10-31

Applicant: G.D. SEARLE & CO. ,  NG, John, S. ,  PRZYBYLA, Claire, A. ,  MUELLER, Richard, A. ,  VASQUEZ, Michael, L. ,  GETMAN, Daniel, P. ,  FRESKOS, John, J. ,  DECRESCENZO, Gary, A. ,  BERTENSHAW, Deborah, E. ,  HEINTZ, Robert, M. ,  ZHANG, Suhong ,  LIU, Chin ,  LANEMAN, Scott, A.

Inventor： G.D. SEARLE & CO.

IPC: C07C215/28

CPC classification number: C07C273/1854 ,  C07B2200/07 ,  C07C213/00 ,  C07C213/02 ,  C07C213/08 ,  C07C215/28 ,  C07C221/00 ,  C07C223/02 ,  C07C253/30 ,  C07C255/26 ,  C07C269/04 ,  C07C271/16 ,  C07C271/18 ,  C07C271/20 ,  C07C273/1827 ,  C07C275/24 ,  C07C309/73 ,  C07D303/36 ,  C07F7/1804 ,  C07C215/08

Abstract: A synthesis is described for intermediates which are readily amenable to the large scale preparation of hydroxyethylurea-based chiral HIV protease inhibitors. The method includes forming a diastereoselective epoxide of cyanohydrin from a chiral alpha amino aldehyde.

Abstract translation: 对于易于大规模制备基于羟基脲的手性HIV蛋白酶抑制剂的中间体描述了合成。 该方法包括由手性α氨基醛形成氰醇的非对映选择性环氧化物。

公开(公告)号：WO2003091247A2

公开(公告)日：2003-11-06

申请号：PCT/US2003/013123

申请日：2003-04-25

Applicant: PHARMACIA CORPORATION ,  BARTA, Thomas, E. ,  BECKER, Daniel, P. ,  BEDELL, Louis, J. ,  BOEHM, Terri, L. ,  BROWN, David, L. ,  CARROLL, Jeffery, N. ,  CHEN, Yiyuan ,  FOBIAN, Yvette ,  FRESKOS, John, N. ,  GASIECKI, Alan, F. ,  GRAPPERHAUS, Margaret ,  HEINTZ, Robert, M. ,  HOCKERMAN, Susan, L. ,  KASSAB, Darren, J. ,  KHANNA, Ish, Kumar ,  KOLODZIEJ, Stephen, A. ,  MASSA, Mark ,  MCDONALD, Joseph ,  MISCHKE, Brent, V. ,  MISCHKE, Deborah, A. ,  MULLINS, Patrick, B. ,  NAGY, Mark ,  NORTON, Monica, B. ,  RICO, Joseph, G. ,  SCHMIDT, Michelle, A. ,  STEHLE, Nathan, W. ,  TALLEY, John, J. ,  VERNIER, William, F. ,  VILLAMILL, Clara, I. ,  WANG, Lijuan, Jane ,  WYNN, Thomas, A.

Inventor： BARTA, Thomas, E. ,  BECKER, Daniel, P. ,  BEDELL, Louis, J. ,  BOEHM, Terri, L. ,  BROWN, David, L. ,  CARROLL, Jeffery, N. ,  CHEN, Yiyuan ,  FOBIAN, Yvette ,  FRESKOS, John, N. ,  GASIECKI, Alan, F. ,  GRAPPERHAUS, Margaret ,  HEINTZ, Robert, M. ,  HOCKERMAN, Susan, L. ,  KASSAB, Darren, J. ,  KHANNA, Ish, Kumar ,  KOLODZIEJ, Stephen, A. ,  MASSA, Mark ,  MCDONALD, Joseph ,  MISCHKE, Brent, V. ,  MISCHKE, Deborah, A. ,  MULLINS, Patrick, B. ,  NAGY, Mark ,  NORTON, Monica, B. ,  RICO, Joseph, G. ,  SCHMIDT, Michelle, A. ,  STEHLE, Nathan, W. ,  TALLEY, John, J. ,  VERNIER, William, F. ,  VILLAMILL, Clara, I. ,  WANG, Lijuan, Jane ,  WYNN, Thomas, A.

IPC: C07D407/12

CPC classification number: C07D213/74 ,  C07D211/66 ,  C07D211/96 ,  C07D309/08 ,  C07D335/02 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/04 ,  C07D409/06 ,  C07D409/12 ,  C07D409/14 ,  C07D411/14 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

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: 本发明一般涉及蛋白酶（也称为“蛋白酶”）抑制剂，特别是涉及抑制基质金属蛋白酶（也称为“基质金属蛋白酶”或“MMP”）的哌啶基和哌嗪基 - 磺酰基甲基异羟肟酸， 活性和/或蛋白聚糖蛋白聚糖酶活性。 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和R x如上定义 在本说明书中），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：WO0071514A8

公开(公告)日：2001-02-22

申请号：PCT/US0009807

申请日：2000-05-17

Applicant: SEARLE & CO ,  BARTA THOMAS E ,  BECKER DANIEL P ,  BEDELL LOUIS J ,  CRESCENZO GARY A DE ,  FRESKOS JOHN N ,  GETMAN DANIEL P ,  HEINTZ ROBERT M ,  HOCKERMAN SUSAN L ,  LI HUI ,  MISCHKE BRENT V ,  VILLAMIL CLARA I

Inventor： BARTA THOMAS E ,  BECKER DANIEL P ,  BEDELL LOUIS J ,  DE CRESCENZO GARY A ,  FRESKOS JOHN N ,  GETMAN DANIEL P ,  HEINTZ ROBERT M ,  HOCKERMAN SUSAN L ,  LI HUI ,  MISCHKE BRENT V ,  VILLAMIL CLARA I

IPC: C07D215/50 ,  A61K31/16 ,  A61K31/164 ,  A61K31/166 ,  A61K31/17 ,  A61K31/18 ,  A61K31/197 ,  A61K31/222 ,  A61K31/27 ,  A61K31/341 ,  A61K31/351 ,  A61K31/4409 ,  A61K31/4453 ,  A61K31/47 ,  A61K38/00 ,  A61P1/02 ,  A61P1/04 ,  A61P7/00 ,  A61P7/02 ,  A61P11/00 ,  A61P13/12 ,  A61P17/02 ,  A61P19/00 ,  A61P19/02 ,  A61P25/28 ,  A61P27/02 ,  A61P29/00 ,  A61P35/04 ,  A61P43/00 ,  C07C317/48 ,  C07C317/50 ,  C07C323/65 ,  C07D207/09 ,  C07D211/14 ,  C07D213/38 ,  C07D307/58 ,  C07D307/68 ,  C07D309/10 ,  C07K5/06 ,  A61K31/10 ,  C07D211/62 ,  C07D213/56 ,  C07D213/81 ,  C07D213/82 ,  C07D295/15 ,  C07D317/58 ,  C07K5/062

CPC classification number: C07K5/06026 ,  A61K38/00 ,  C07C317/48 ,  C07C317/50 ,  C07C323/65 ,  C07D307/58

Abstract: A family of molecules of formula (A) in which R is a 5- or 6-membered carbocyclo, heterocyclo, aryl or heteroaryl radical such that its size defined by certain parameters; R is -O-R , -NR -O-R or -NR -O-R ; and the other variables are as defined in the claims, is disclosed that inhibit matrix metalloproteinase (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. Also disclosed are process for preparing a contemplated compound and for treating a mammal having a condition associated with pathological matrix metalloproteinase activity.

Abstract translation: 式（A）的分子族，其中R 1是5-或6-元碳环，杂环基，芳基或杂芳基，使得其大小由某些参数定义; R 20是-O-R 21，-NR 13 -O-R 22或-NR 13 -O-R 14; 并且其它变量如权利要求中所定义，公开了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，同时通常表现出很小的活性 针对MMP-1。 预期的化合物也对TNF的产生几乎没有抑制作用。 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。