公开(公告)号：EP1140902A1

公开(公告)日：2001-10-10

申请号：EP99963980.0

申请日：1999-12-16

申请人： SCHERING CORPORATION

发明人： TAVERAS, Arthur, G. ,  DOLL, Ronald, J. ,  COOPER, Alan, B. ,  FERREIRA, Johan, A. ,  GUZI, Timothy ,  MALLAMS, Alan, K. ,  RANE, Dinanath, F. ,  GIRIJAVALLABHAN, Viyyoor, M. ,  AFONSO, Adriano ,  AKI, Cynthia, J. ,  CHAO, Jianping ,  ALVAREZ, Carmen ,  KELLY, Joseph, M. ,  LALWANI, Tarik ,  DESAI, Jagdish, A. ,  WANG, James, J., S. ,  WEINSTEIN, Jay

IPC分类号： C07D401/14 ,  C07D413/14 ,  C07D407/14 ,  A61K31/445 ,  A61K31/44 ,  A61K31/55 ,  A61P35/00

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/12 ,  C07D401/14

摘要： Disclosed are compounds of formula (1.0) wherein R13 represents an imidazole ring; R14 represents a carbamate, urea, amide or sulfonamide group; R8 represents H when the alkyl chain between the amide group and the R13 imidazole group is substituted, or R8 represents a substituent such aa arylalkyl, heteroarylalkyl or cycloalkyl; and the remaining substituents are as defined herein. Also disclosed are compounds wherein R8 is H, and the alkyl chain between the amide group and the R13 imidazole group is unsubstituted. Also disclosed is a method of treating cancer and a method of inhibiting farnesyl protein transferase using the disclosed compounds.

摘要翻译： 公开了式（1.0）的化合物，其中R 13代表咪唑环; R14代表氨基甲酸酯，脲，酰胺或磺酰胺基团; 当酰胺基团和R13咪唑基团之间的烷基链被取代时，R8表示H，或者R8表示取代基如芳烷基，杂芳基烷基或环烷基; 其余的取代基如本文所定义。 还公开了其中R 8为H且酰胺基团和R 13咪唑基团之间的烷基链未被取代的化合物。 还公开了使用所公开的化合物治疗癌症的方法和抑制法呢基蛋白转移酶的方法。

公开(公告)号：EP0942906B1

公开(公告)日：2004-11-03

申请号：EP97955043.1

申请日：1997-09-11

申请人： SCHERING CORPORATION

发明人： NJOROGE, F., George ,  TAVERAS, Arthur, G. ,  DOLL, Ronald, J. ,  LALWANI, Tarik ,  ALVAREZ, Carmen ,  REMISZEWSKI, Stacy, W.

IPC分类号： C07D401/04 ,  A61K31/55 ,  C07D401/14

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

摘要： Novel tricyclic compounds of Formula (1.0) are disclosed. Compounds of Formula (1.0) are represented by the compounds of formulas (1.4) or (1.5) wherein R?1, R3 and R4¿ are each independently selected from halo. Also disclosed are methods of inhibiting farnesyl protein transferase and the growth of abnormal cells, such as tumor cells.

公开(公告)号：EP0942906A2

公开(公告)日：1999-09-22

申请号：EP97955043.0

申请日：1997-09-11

申请人： SCHERING CORPORATION

发明人： NJOROGE, F., George ,  TAVERAS, Arthur, G. ,  DOLL, Ronald, J. ,  LALWANI, Tarik ,  ALVAREZ, Carmen ,  REMISZEWSKI, Stacy, W.

IPC分类号： A61K31 ,  A61P35 ,  A61P43 ,  C07D401 ,  C07D405 ,  C07D409 ,  C07D413 ,  C07D417 ,  C07D471 ,  C07D521

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

摘要： Novel tricyclic compounds of Formula (1.0) are disclosed. Compounds of Formula (1.0) are represented by the compounds of formulas (1.4) or (1.5) wherein R?1, R3 and R4¿ are each independently selected from halo. Also disclosed are methods of inhibiting farnesyl protein transferase and the growth of abnormal cells, such as tumor cells.

公开(公告)号：EP0934303B1

公开(公告)日：2004-12-29

申请号：EP97946875.8

申请日：1997-09-11

申请人： SCHERING CORPORATION

发明人： TAVERAS, Arthur, G. ,  MALLAMS, Alan, K. ,  AFONSO, Adriano ,  REMISZEWSKI, Stacy, W. ,  NJOROGE, F., George ,  DOLL, Ronald, J. ,  LALWANI, Tarik ,  ALVAREZ, Carmen

IPC分类号： C07D401/00

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

摘要： Novel tricyclic compounds of formula (1.0) are disclosed. Compounds of formula (1.0) are represented by the compounds of formulas (1.4) or (1.5) wherein R?1, R3 and R4¿ are each independently selected from halo. Also disclosed are methods of inhibiting farnesyl protein transferase and the growth of abnormal cells, such as tumor cells.

公开(公告)号：EP0991643A1

公开(公告)日：2000-04-12

申请号：EP98928892.3

申请日：1998-06-15

申请人： SCHERING CORPORATION

发明人： DOLL, Ronald, J. ,  LALWANI, Tarik

IPC分类号： C07D401/14 ,  C07D401/04 ,  A61K31/47 ,  C07D409/14 ,  C07D405/14

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14

摘要： Novel aminooxyamide tricyclic compounds and pharmaceutical compositions are disclosed which are inhibitors of the enzyme, farnesyl protein transferase. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel aminooxyamide tricyclic compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human.

公开(公告)号：EP0991643B1

公开(公告)日：2003-04-02

申请号：EP98928892.3

申请日：1998-06-15

申请人： SCHERING CORPORATION

发明人： DOLL, Ronald, J. ,  LALWANI, Tarik

IPC分类号： C07D401/14 ,  C07D401/04 ,  A61K31/47 ,  C07D409/14 ,  C07D405/14

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14

摘要： Novel aminooxyamide tricyclic compounds and pharmaceutical compositions are disclosed which are inhibitors of the enzyme, farnesyl protein transferase. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel aminooxyamide tricyclic compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human.

公开(公告)号：EP0993459B1

公开(公告)日：2002-11-06

申请号：EP98926276.1

申请日：1998-06-15

申请人： SCHERING CORPORATION

发明人： REMISZEWSKI, Stacy, W. ,  DOLL, Ronald, J. ,  ALVAREZ, Carmen ,  LALWANI, Tarik

IPC分类号： C07D401/08 ,  C07D405/14 ,  A61K31/55 ,  C07D491/113 ,  C07D495/10 ,  C07D413/14 ,  C07F7/18

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D491/10 ,  C07D495/10 ,  C07F7/1856

摘要： Novel compounds of formula (1.0) are disclosed. In formula (1.0) a represents N or NO, R?1 and R3¿ are halo, R?2 and R4¿ are independently H or halo provided that at least one is H, X is C, CH or N, and R represents a cycloalkyl or a heterocycloalkyl ring that is substitued. Also disclosed are methods of inhibiting farnesyl protein transferase and methods for treating tumor cells.

公开(公告)号：EP0989978A1

公开(公告)日：2000-04-05

申请号：EP98928891.5

申请日：1998-06-15

申请人： SCHERING CORPORATION

发明人： DOLL, Ronald, J. ,  LALWANI, Tarik ,  ALVAREZ, Carmen

IPC分类号： C07D401/04 ,  A61K31/55

CPC分类号： C07D401/04

摘要： Compounds of formula (I) useful for inhibiting Ras function and therefore inhibiting or treating the abnormal growth of cells farnesyl protein transferase inhibitors are disclosed or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof, wherein, R and R2 are halo; R?1 and R3¿ are H and halo, provided that at least one of R?1 and R3¿ is H; X is N, CH or C, when the double bond is present at the C-11 position; R4 is =O, -NHOH, -N=NHR6, -N=NHSO¿2R?6, -N=NHCOR6, -N=NHCONH¿2?, -N=NHCOCONH2, (H, OH), (H, -OR?6¿), (H, -OCOR6), (H, OSO¿2R?6) or -E-(CH¿2?)n1-G-, wherein n1 is 1 to 5, and E and G are O, S or N, and are joined to the same carbon to form a cyclic structure; R?5¿ is H, lower alkyl, or optionally substituted aryl, heteroaryl, aralkyl, heteroaralkyl or heterocycloalkyl-alkyl; R6 is lower alkyl or optionally substituted aryl, heteroaryl, aralkyl, heteroaralkyl or heterocycloalkyl-alkyl; R?7, R8 and R9¿ are independently selected from the group consisting of H, lower alkyl, aryl, and aralkyl; and n is 0-5.

公开(公告)号：EP0989978B1

公开(公告)日：2007-03-14

申请号：EP98928891.5

申请日：1998-06-15

申请人： SCHERING CORPORATION

发明人： DOLL, Ronald, J. ,  LALWANI, Tarik ,  ALVAREZ, Carmen

IPC分类号： C07D401/04 ,  A61K31/55

CPC分类号： C07D401/04

摘要： Compounds of formula (I) useful for inhibiting Ras function and therefore inhibiting or treating the abnormal growth of cells farnesyl protein transferase inhibitors are disclosed or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof, wherein, R and R2 are halo; R?1 and R3¿ are H and halo, provided that at least one of R?1 and R3¿ is H; X is N, CH or C, when the double bond is present at the C-11 position; R4 is =O, -NHOH, -N=NHR6, -N=NHSO¿2R?6, -N=NHCOR6, -N=NHCONH¿2?, -N=NHCOCONH2, (H, OH), (H, -OR?6¿), (H, -OCOR6), (H, OSO¿2R?6) or -E-(CH¿2?)n1-G-, wherein n1 is 1 to 5, and E and G are O, S or N, and are joined to the same carbon to form a cyclic structure; R?5¿ is H, lower alkyl, or optionally substituted aryl, heteroaryl, aralkyl, heteroaralkyl or heterocycloalkyl-alkyl; R6 is lower alkyl or optionally substituted aryl, heteroaryl, aralkyl, heteroaralkyl or heterocycloalkyl-alkyl; R?7, R8 and R9¿ are independently selected from the group consisting of H, lower alkyl, aryl, and aralkyl; and n is 0-5.

公开(公告)号：EP1019398B1

公开(公告)日：2004-09-15

申请号：EP98932714.3

申请日：1998-06-15

申请人： SCHERING CORPORATION

发明人： DOLL, Ronald, J. ,  ALVAREZ, Carmen ,  LALWANI, Tarik ,  LIU, Yi-Tsung

IPC分类号： C07D405/14 ,  C07D409/14 ,  C07D493/08 ,  C07D405/12 ,  C07D401/04 ,  C07D221/16 ,  A61K31/435

CPC分类号： C07D401/04 ,  C07D221/16 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D493/08

摘要： Novel compounds of formula (1.0) are disclosed. In Formula (1.0) a represents N or NO, R?1 and R3¿ are halo, R?2 and R4¿ are independently H or halo provided that at least one is H, X is C, CH or N, and T represents a five or six membered heterocycloalkyl ring having one or two heteroatoms selected from S or O. Also disclosed are methods of inhibiting farnesyl protein transferase and methods for treating tumor cells.