公开(公告)号：EP1107959A2

公开(公告)日：2001-06-20

申请号：EP99949568.2

申请日：1999-08-27

申请人： SCIOS INC.

发明人： CHAKRAVARTY, Sarvajit ,  DUGAR, Sundeep ,  PERUMATTAM, John, J. ,  SCHREINER, George, F. ,  LIU, David, Y. ,  LEWICKI, John, A.

IPC分类号： C07D239/91 ,  C07D215/00 ,  C07D239/72 ,  A61P29/00 ,  A61K31/505 ,  A61K31/47

CPC分类号： C07D401/12 ,  A61K31/519 ,  C07D239/94 ,  C07D471/04

摘要： The invention is directed to methods to inhibit TGF-β and/or p38-α kinase using compounds of formula (1) or the pharmaceutically acceptable salts thereof wherein R3 is a noninterfering substituent; each Z is CR2 or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N; each R2 is independently a noninterfering substituent; L is a linker; n is 0 or 1; and Ar' is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents.

公开(公告)号：EP1107959B1

公开(公告)日：2006-10-11

申请号：EP99949568.2

申请日：1999-08-27

申请人： SCIOS INC.

发明人： CHAKRAVARTY, Sarvajit ,  DUGAR, Sundeep ,  PERUMATTAM, John, J. ,  SCHREINER, George, F. ,  LIU, David, Y. ,  LEWICKI, John, A.

IPC分类号： C07D239/91 ,  C07D215/00 ,  C07D239/72 ,  A61P29/00 ,  A61K31/505 ,  A61K31/47

CPC分类号： C07D401/12 ,  A61K31/519 ,  C07D239/94 ,  C07D471/04

摘要： The invention is directed to methods to inhibit TGF-β and/or p38-α kinase using compounds of formula (1) or the pharmaceutically acceptable salts thereof wherein R3 is a noninterfering substituent; each Z is CR2 or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N; each R2 is independently a noninterfering substituent; L is a linker; n is 0 or 1; and Ar' is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents.

公开(公告)号：EP1699767A2

公开(公告)日：2006-09-13

申请号：EP04816043.6

申请日：2004-12-31

申请人： Scios, Inc.

发明人： CHAKRAVARTY, Sarvajit ,  DUGAR, Sundeep ,  TESTER, Richland ,  CONTE, Aurelia

IPC分类号： C07D239/90 ,  C07D239/91 ,  C07D471/04

CPC分类号： C07D239/91 ,  C07D471/04

摘要： The present invention is directed to a rpocess for making 2-substituted pyridopyrimidones. In particular, 2-substituted pyridopyrimidones are made through the single step reaction of suitable acid derivatives with desired derivatives of amidines.

摘要翻译： 本发明涉及制备2-取代的吡啶并嘧啶酮的方法。 具体地说，2-取代的吡啶并嘧啶酮是通过合适的酸衍生物与期望的脒衍生物的单步反应制备的。

公开(公告)号：EP1608631A2

公开(公告)日：2005-12-28

申请号：EP04758392.7

申请日：2004-03-26

申请人： SCIOS INC.

发明人： DUGAR, Sundeep ,  CHAKRAVARTY, Sarvajit ,  CONTE, Aurelia ,  AXON, Jonathan ,  MCENROE, Glenn

IPC分类号： C07D239/70 ,  C07D487/04 ,  C07D491/048 ,  C07D495/04

CPC分类号： C07D487/04 ,  A61K31/517 ,  C07D239/94 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D413/14 ,  C07D471/04 ,  C07D491/04 ,  C07D493/04 ,  C07D495/04 ,  C07D498/04

摘要： Compounds in which a pyrimidine nucleus is bridged at the (5) and (6) position and are further substituted at positions (2) and (4) with substituents comprising aromatic moieties are useful in treating subjects with conditions ameliorated by inhibition of TGFβ activity.

摘要翻译： 其中嘧啶核在（5）和（6）位桥接并且在位置（2）和（4）处用包含芳族部分的取代基进一步取代的化合物可用于治疗患有通过抑制TGFβ活性而改善的病症的受试者。

公开(公告)号：EP1675830A2

公开(公告)日：2006-07-05

申请号：EP04789449.8

申请日：2004-09-30

申请人： SCIOS INC.

发明人： DUGAR, Sundeep ,  MCENROE, Glen ,  CHAKRAVARTY, Sarvajit ,  MURPHY, Alison ,  PERUMATTAM, John, Joseph ,  CONTE, Aurelia

IPC分类号： C07D213/75

CPC分类号： C07D405/12 ,  C07D213/75 ,  C07D239/48 ,  C07D401/12 ,  C07D405/14 ,  C07D409/12 ,  C07D417/12

摘要： The invention is directed to compounds and methods to inhibit p38 kinase wherein the compounds are a pyrimidine or pyridine coupled to two mandatory substituents.

公开(公告)号：EP1549316A1

公开(公告)日：2005-07-06

申请号：EP03754501.9

申请日：2003-09-10

申请人： SCIOS INC.

发明人： AXON, Jonathan ,  CHAKRAVARTY, Sarvajit ,  DUGAR, Sundeep ,  McENROE, Glen ,  MURPHY, Alison

IPC分类号： A61K31/505 ,  A61K31/506 ,  A61K31/53 ,  C07D239/32 ,  C07D251/14 ,  C07D403/12

CPC分类号： C07D409/14 ,  C07D239/42 ,  C07D401/12 ,  C07D405/14 ,  C07D413/14

摘要： Certain appropriately substituted forms of pyrimidine and triazine are useful in the treatment to conditions associated with enhanced TGFβ activity.

公开(公告)号：EP1545528A2

公开(公告)日：2005-06-29

申请号：EP03749429.1

申请日：2003-09-03

申请人： SCIOS INC.

发明人： CHAKRAVARTY, Sarvajit ,  DUGAR, Sundeep ,  LU, Qing ,  LUEDTKE, Gregory, R. ,  MAVUNKEL, Babu, J. ,  PERUMATTAM, John, Joseph ,  TESTER, Richland

IPC分类号： A61K31/496 ,  A61K31/454 ,  C07D401/10 ,  C07D403/10 ,  C07D409/14

CPC分类号： C07D401/06 ,  C07D209/18 ,  C07D209/42 ,  C07D401/14 ,  C07D403/06 ,  C07D409/12 ,  C07D409/14

摘要： The invention is directed to methods to inhibit p38-α kinase using compounds comprising a phenyl or thienyl coupled through a piperidine or piperazine nucleus to an indole residue wherein the indole residue mandatorily has a substituent on the ring nitrogen which is an amino or substituted amino group.

公开(公告)号：EP1511738A1

公开(公告)日：2005-03-09

申请号：EP03726892.7

申请日：2003-05-16

申请人： Scios Inc.

发明人： CHAKRAVARTY, Sarvajit ,  DUGAR, Sundeep ,  HIGGINS, Linda, S. ,  KAPOUN, Ann, M. ,  LIU, David, Y. ,  SCHREINER, George, F. ,  PROTTER, Andrew, A. ,  TRAN, Thomas-Toan

IPC分类号： C07D239/42 ,  C07D239/94 ,  C07D471/04

CPC分类号： A61K31/435 ,  A61K31/495 ,  A61K31/53

摘要： The invention concerns methods of treating fibroproliferative disorders associated with TGF-β signaling, by administering non-peptide small molecule inhibitors of TGF-β specifically binding to the type I TGF-β receptor (TGFβ-R1). Preferably, the inhibitors are quinazoline derivatives. The invention also concerns methods for reversing the effect of TGF-β mediated cell activation on the expression of a gene associated with fibrosis, comprising contacting a cell or tissue in which the expression of such gene is altered as a result of TGF-β mediated cell activation, with a non-peptide small molecule inhibitor of TGF-β, specifically binding a TGFβ-R1 receptor kinase present in the cell or tissue.

公开(公告)号：EP1178983B1

公开(公告)日：2007-10-24

申请号：EP00939322.4

申请日：2000-05-19

申请人： SCIOS INC.

发明人： MAVUNKEL, Babu, J. ,  CHAKRAVARTY, Sarvajit ,  PERUMATTAM, John, J. ,  DUGAR, Sundeep ,  LU, Qing ,  LIANG, Xi

IPC分类号： C07D401/06 ,  A61K31/404 ,  A61P43/00 ,  C07D209/24 ,  C07D401/14

CPC分类号： C07D401/06 ,  C07D209/24 ,  C07D401/14

摘要： The invention is directed to methods to inhibit p38-α kinase using compounds of formula (1), and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein (a) represents a single or double bond; one Z2 is CA or CR8A and the other is CR1, CR12, NR6 or N wherein each R?1, R6 and R8¿ is independently hydrogen or noninterfering substituent; A is -W¿i?-COXjY wherein Y is COR?2¿ or an isostere thereof and R2 is hydrogen or a noninterfering substituent, each of W and X is a spacer of 2-6Å, and each of i and j is independently 0 or 1; Z?3 is NR7¿ or O; each R3 is independently a noninterfering substituent; n is 0-3; each of L?1 and L2¿ is a linker; each R4 is independently a noninterfering substituent; m is 0-4; Z?1 is CR5¿ or N wherein R5 is hydrogen or a noninterfering substituent; each of l and k is an integer from 0-2 wherein the sum of l and k is 0-3; Ar is an aryl group substituted with 0-5 noninterfering substituents, wherein two noninterfering substituents can form a fused ring; and the distance between the atom of Ar linked to L2 and the center of the α ring is 4.5-24Å.

公开(公告)号：EP1178983A1

公开(公告)日：2002-02-13

申请号：EP00939322.4

申请日：2000-05-19

申请人： Scios Inc.

发明人： MAVUNKEL, Babu, J. ,  CHAKRAVARTY, Sarvajit ,  PERUMATTAM, John, J. ,  DUGAR, Sundeep ,  LU, Qing ,  LIANG, Xi

IPC分类号： C07D401/06 ,  A61K31/404 ,  A61P43/00 ,  C07D209/24 ,  C07D401/14

CPC分类号： C07D401/06 ,  C07D209/24 ,  C07D401/14

摘要： The invention is directed to methods to inhibit p38-α kinase using compounds of formula (1), and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein (a) represents a single or double bond; one Z2 is CA or CR8A and the other is CR1, CR12, NR6 or N wherein each R?1, R6 and R8¿ is independently hydrogen or noninterfering substituent; A is -W¿i?-COXjY wherein Y is COR?2¿ or an isostere thereof and R2 is hydrogen or a noninterfering substituent, each of W and X is a spacer of 2-6Å, and each of i and j is independently 0 or 1; Z?3 is NR7¿ or O; each R3 is independently a noninterfering substituent; n is 0-3; each of L?1 and L2¿ is a linker; each R4 is independently a noninterfering substituent; m is 0-4; Z?1 is CR5¿ or N wherein R5 is hydrogen or a noninterfering substituent; each of l and k is an integer from 0-2 wherein the sum of l and k is 0-3; Ar is an aryl group substituted with 0-5 noninterfering substituents, wherein two noninterfering substituents can form a fused ring; and the distance between the atom of Ar linked to L2 and the center of the α ring is 4.5-24Å.