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：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：WO2012145569A1

公开(公告)日：2012-10-26

申请号：PCT/US2012/034349

申请日：2012-04-20

Applicant: SIGNAL PHARMACEUTICALS, LLC ,  BENNETT, Brydon, L. ,  ELSNER, Jan ,  ERDMAN, Paul ,  HILGRAF, Robert ,  LEBRUN, Laurie, Ann ,  MCCARRICK, Meg ,  MOGHADDAM, Mehran, F. ,  NAGY, Mark, A. ,  NORRIS, Stephen ,  PAISNER, David, A. ,  SLOSS, Marianne ,  ROMANOW, William, J. ,  SATOH, Yoshitaka ,  TIKHE, Jayashree ,  YOON, Won, Hyung ,  DELGADO, Mercedes

Inventor： BENNETT, Brydon, L. ,  ELSNER, Jan ,  ERDMAN, Paul ,  HILGRAF, Robert ,  LEBRUN, Laurie, Ann ,  MCCARRICK, Meg ,  MOGHADDAM, Mehran, F. ,  NAGY, Mark, A. ,  NORRIS, Stephen ,  PAISNER, David, A. ,  SLOSS, Marianne ,  ROMANOW, William, J. ,  SATOH, Yoshitaka ,  TIKHE, Jayashree ,  YOON, Won, Hyung ,  DELGADO, Mercedes

IPC: C07D239/48 ,  C07D405/02 ,  C07D401/12 ,  C07D409/12

CPC classification number: C07D239/48 ,  A61K31/505 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12

Abstract: Provided herein are Diaminopyrimidine Compounds having the following structures: wherein R 1 , R 2 , R 3, and R 4 are as defined herein, compositions comprising an effective amount of a Diaminopyrimidine Compound, and methods for treating or preventing liver fibrotic disorders or a condition treatable or preventable by inhibition of a JNK pathway.

Abstract translation: 本文提供具有以下结构的二氨基嘧啶化合物：其中R1，R2，R3和R4如本文所定义，包含有效量的二氨基嘧啶化合物的组合物，以及用于治疗或预防肝纤维化疾病的方法或可治疗或可预防的病症 抑制JNK通路。

公开(公告)号：WO2019014100A1

公开(公告)日：2019-01-17

申请号：PCT/US2018/041230

申请日：2018-07-09

Applicant: CELGENE CORPORATION ,  ALEXANDER, Matthew, D. ,  ARTMAN, Gerald, D., III ,  BRAY, Gordon, L. ,  CARMICHAEL, James ,  CARRANCIO, Soraya ,  CATHERS, Brian E. ,  CORREA, Matthew, D. ,  HANSEN, Joshua ,  HAVENS, Courtney, G. ,  KERCHER, Timothy, S. ,  LOPEZ-GIRONA, Antonia ,  LU, Xiaoling ,  MAN, Hon-Wah ,  NAGY, Mark, A. ,  NARLA, Rama, K. ,  PICCOTTI, Joseph, R. ,  PIERCE, Daniel, W. ,  TAVARES-GRECO, Paula, A. ,  WHITEFIELD, Brandon, W. ,  WONG, Lilly, L. ,  ZOU, Nanfei

Inventor： ALEXANDER, Matthew, D. ,  ARTMAN, Gerald, D., III ,  BRAY, Gordon, L. ,  CARMICHAEL, James ,  CARRANCIO, Soraya ,  CATHERS, Brian E. ,  CORREA, Matthew, D. ,  HANSEN, Joshua ,  HAVENS, Courtney, G. ,  KERCHER, Timothy, S. ,  LOPEZ-GIRONA, Antonia ,  LU, Xiaoling ,  MAN, Hon-Wah ,  NAGY, Mark, A. ,  NARLA, Rama, K. ,  PICCOTTI, Joseph, R. ,  PIERCE, Daniel, W. ,  TAVARES-GRECO, Paula, A. ,  WHITEFIELD, Brandon, W. ,  WONG, Lilly, L. ,  ZOU, Nanfei

IPC: A61K31/496 ,  C07D241/02 ,  A61K38/05 ,  A61K31/573 ,  A61P35/00

Abstract: Provided herein is 4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile, or an enantiomer, a mixture of enantiomers, a tautomer, or a pharmaceutically acceptable salt thereof, and methods for treating, preventing or managing multiple myeloma using such compounds. Also provided are pharmaceutical compositions comprising the compounds, and methods of use of the compositions.