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：EP1080078A1

公开(公告)日：2001-03-07

申请号：EP99924412.2

申请日：1999-05-21

申请人： SCIOS INC.

发明人： MAVUNKEL, Babu, J. ,  LIU, David, Y. ,  SCHREINER, George, F. ,  LEWICKI, John, A. ,  PERUMATTAM, John, J.

IPC分类号： C07D235/06 ,  C07D401/06 ,  C07D401/14 ,  C07D209/08 ,  C07D403/06 ,  A61K31/445 ,  A61K31/40 ,  A61K31/41

CPC分类号： C07D209/08 ,  C07D235/06 ,  C07D401/06 ,  C07D401/14 ,  C07D403/06

摘要： Compounds of formulae α or β, and the pharmaceutically acceptable salts thereof, wherein each of Z?1 and Z2¿ is independently CR4 or N; where each R4 is independently H or is alkyl (1-6C) or aryl, each of said alkyl or aryl optionally including one or more heteroatoms selected from O, S and N and optionally substituted by one or more of halo, OR, SR, NR¿2?, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl (1-6C), or by one or more CN or =O, or by one or more aliphatic or aromatic 5- or 6-membered rings optionally containing 1-2 heteroatoms; R?1¿ is formula (I); wherein X1 is CO or an isostere thereof; m is 0 or 1; Y is optionally substituted alkyl, optionally substituted aryl, or optionally substituted arylalkyl or two Y taken together may form an alkylene (2-3C) bridge; n is 0 or 2; Z3 is CH or N; X2 is CH, CH¿2? or an isostere thereof; and Ar consists of one or two phenyl moieties directly coupled to X?2¿ optionally substituted by halo, nitro, alkyl(1-6C), alkenyl(1-6C), alkynyl(1-6C), CN or CF¿3?, or by RCO, COOR, CONR2, NR2, OR, SR, OOCR or NROCR wherein R is H or alkyl(1-6C) or by phenyl, itself optionally substituted by the foregoing substituents; R?2¿ is H, or is alkyl(1-6C) or aryl, each or said alkyl or aryl optionally including one heteroatome which is O, S or N, and optionally substituted by one or more of halo, OR, SR, NR¿2?, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl(1-6C), alkynyl(1-6C), or by one or more CN or =O, or by one or more aliphatic or aromatic 5- or 6-membered rings optionally containing 1-2 heteroatoms; R?3¿ is H, halo, NO¿2?, alkyl(1-6C), alkenyl(1-6C), alkynyl(1-6C), CN, OR, SR, NR2, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl(1-6C) are disclosed. These compounds are selective inhibitors of p38α kinase.

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：EP1080078B1

公开(公告)日：2006-02-01

申请号：EP99924412.2

申请日：1999-05-21

申请人： SCIOS INC.

发明人： MAVUNKEL, Babu, J. ,  LIU, David, Y. ,  SCHREINER, George, F. ,  LEWICKI, John, A. ,  PERUMATTAM, John, J.

IPC分类号： C07D235/06 ,  C07D401/06 ,  C07D401/14 ,  C07D209/08 ,  C07D403/06 ,  A61K31/445 ,  A61K31/40 ,  A61K31/41

CPC分类号： C07D209/08 ,  C07D235/06 ,  C07D401/06 ,  C07D401/14 ,  C07D403/06

摘要： Compounds of formulae α or β, and the pharmaceutically acceptable salts thereof, wherein each of Z?1 and Z2¿ is independently CR4 or N; where each R4 is independently H or is alkyl (1-6C) or aryl, each of said alkyl or aryl optionally including one or more heteroatoms selected from O, S and N and optionally substituted by one or more of halo, OR, SR, NR¿2?, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl (1-6C), or by one or more CN or =O, or by one or more aliphatic or aromatic 5- or 6-membered rings optionally containing 1-2 heteroatoms; R?1¿ is formula (I); wherein X1 is CO or an isostere thereof; m is 0 or 1; Y is optionally substituted alkyl, optionally substituted aryl, or optionally substituted arylalkyl or two Y taken together may form an alkylene (2-3C) bridge; n is 0 or 2; Z3 is CH or N; X2 is CH, CH¿2? or an isostere thereof; and Ar consists of one or two phenyl moieties directly coupled to X?2¿ optionally substituted by halo, nitro, alkyl(1-6C), alkenyl(1-6C), alkynyl(1-6C), CN or CF¿3?, or by RCO, COOR, CONR2, NR2, OR, SR, OOCR or NROCR wherein R is H or alkyl(1-6C) or by phenyl, itself optionally substituted by the foregoing substituents; R?2¿ is H, or is alkyl(1-6C) or aryl, each or said alkyl or aryl optionally including one heteroatome which is O, S or N, and optionally substituted by one or more of halo, OR, SR, NR¿2?, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl(1-6C), alkynyl(1-6C), or by one or more CN or =O, or by one or more aliphatic or aromatic 5- or 6-membered rings optionally containing 1-2 heteroatoms; R?3¿ is H, halo, NO¿2?, alkyl(1-6C), alkenyl(1-6C), alkynyl(1-6C), CN, OR, SR, NR2, RCO, COOR, CONR2, OOCR, or NROCR where R is H or alkyl(1-6C) are disclosed. These compounds are selective inhibitors of p38α kinase.

公开(公告)号：EP1107758A2

公开(公告)日：2001-06-20

申请号：EP99945316.0

申请日：1999-08-27

申请人： SCIOS INC.

发明人： GOEHRING, R., Richard ,  LUEDTKE, Gregory, R. ,  MAVUNKEL, Babu, J. ,  CHAKRAVARTY, Sarvajit ,  DUGAR, Sundeep ,  SCHREINER, George, F. ,  LIU, David, Y. ,  LEWICKI, John, A.

IPC分类号： A61K31/445 ,  A61K31/495

CPC分类号： A61K45/06 ,  A61K31/00 ,  A61K31/426 ,  A61K31/4365 ,  A61K31/437 ,  A61K31/445 ,  A61K31/4535 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/495 ,  A61K31/496 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/506 ,  A61K31/519 ,  A61K31/522 ,  Y02A50/411

摘要： The invention is directed to methods to treat conditions mediated by p38-alphakinase using compounds of the formulaand the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof,whereinZ is N or CR1, R1 is a noninterfering substituent,each of X1 and X2 is a linker,Ar1 and Ar2 are identical or different, and represent optionally substituted C1-C20 hydrocarbyl residues wherein at least one of Ar1 and Ar2 is an optionally substituted aryl group, with the proviso that when X2 is CH2 or an isostere thereof, X1 is CO or an isostere thereof, and Ar2 is optionally substituted phenyl, Ar1 is other than an optionally substituted indolyl, benzimidazolyl or benzotriazolyl substituent, and wherein said optionally substituted phenyl is not an optionally substituted indolyl, benzimidazolyl, or benzotriazolyl,Y is a noninterfering substituent, wherein n is an integer from 0-4, andwherein m is an integer from 0-4 and 1 is an integer from 0-3.

摘要翻译： 本发明涉及使用下式的化合物及其药学上可接受的盐或其药物组合物治疗由p38-阿拉蛋白酶介导的病症的方法，其中Z是N或CR1，R1是不干扰取代基，X1和X2各自为 接头，Ar1和Ar2相同或不同，并且表示任选取代的C 1 -C 20烃基残基，其中Ar 1和Ar 2中的至少一个是任选取代的芳基，条件是当X 2是CH 2或其等同体时，X 1是CO 或其等同物，Ar 2是任选取代的苯基，Ar 1不同于任选取代的吲哚基，苯并咪唑基或苯并三唑基取代基，并且其中所述任选取代的苯基不是任选取代的吲哚基，苯并咪唑基或苯并三唑基，Y是不干扰取代基， 其中n是0-4的整数，其中m是0-4的整数，1是0-3的整数。

公开(公告)号：EP1140137A2

公开(公告)日：2001-10-10

申请号：EP99964277.0

申请日：1999-12-15

申请人： SCIOS INC.

发明人： STANTON, Lawrence, W. ,  WHITE, R., Tyler ,  DAMM, Deborah, L. ,  LEWICKI, John, A. ,  JOLY, Alison ,  SCHREINER, George, F.

IPC分类号： A61K38/17 ,  C07K14/47 ,  C12Q1/68 ,  A61K38/18 ,  C07K14/475 ,  C12N15/12

CPC分类号： C12Q1/6883 ,  C12Q2600/158

摘要： The present invention relates to methods and compositions for the detection, diagnosis, prevention and treatment of a disease, specifically cardiac, kidney or inflammatory disease, and related disorders. The present invention also relates to compositions and methods useful in the diagnosis, prevention and therapeutic treatment of a disease, specifically cardiac, kidney or inflammatory disease. Specifically, methods and compositions are provided for the diagnostic evaluation and prognosis of conditions involving a disease, specifically cardiac, kidney or inflammatory disease, for the identification of subjects exhibiting a predisposition to such conditions, for modulating the effect of these differentially expressed genes, for monitoring patients undergoing clinical evaluation for the prevention and treatment of a disease, specifically cardiac, kidney or inflammatory disease, and its disorders, and for monitoring the efficacy of compounds used in clinical trials.