公开(公告)号：EP1019382A1

公开(公告)日：2000-07-19

申请号：EP97954520.9

申请日：1997-12-01

申请人： AXYS PHARMACEUTICALS, INC.

发明人： CHURCH, Timothy, J. ,  CUTSHALL, Neil, Scott ,  GANGLOFF, Anthony, R. ,  JENKINS, Thomas, E. ,  LINSELL, Martin, S. ,  LITVAK, Joane ,  RICE, Kenneth, D. ,  SPENCER, Jeffrey, R. ,  WANG, Vivian, R.

IPC分类号： C07D235/20 ,  A61K31/415 ,  C07D401/14 ,  C07D403/14 ,  C07D413/14 ,  C07D413/06 ,  C07D471/04 ,  C07D498/04

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D235/20 ,  C07D249/08 ,  C07D401/14 ,  C07D403/14 ,  C07D413/06 ,  C07D413/14 ,  C07D471/04 ,  C07F7/0812

摘要： Novel compounds, compositions and methods effective for the prevention and treatment of mast-cell mediated inflammatory disorders are described. A preferred aspect of the invention are compounds of Formula (II) in which: the dashed lines independently represent optional bonds; each R2 independently is (C¿1-6?)alkyl, (C1-6)alkyloxy, halo or hydroxy; each R?3¿ independently is (C¿1-6?)alkyl, (C1-6)alkyloxy, halo or hydroxy; X?3¿ is -C(O)- or -CR?7R8-, X8¿ is -CH(R1)n1- or -C(R1)n1=, wherein R1 is amino(N¿1-4?)azolidinyl, amino(N1-4)azolyl, (N1-4)azolidinyl, (N1-4)azolyl, -NHC(NH)NR?9R9, -C(NR9)R9¿, -C(NH)NHR10, -C(NH)NR10R10 or -(CR11R11)yNH2, or X8 is -N= or -NH(R1)n1-, wherein R1 is -C(NR9)R9, -C(NH)NHR10 or -C(NH)NR10R10, wherein each R9 independently is hydrogen or (C¿1-6?)alkyl and each R?10¿ independently is (C¿1-6?)alkyl; and X?9¿ is -CH(R4)- or -C(R4)=, wherein R?4 is -R12, -OR12, -N(R13)R12, -SR12¿, -S(O)R12, -S(O)¿2R?12, -S(O)¿2OR?12, -S(O)¿2?N(R?13)R12, -N(R13)S(O)¿2R12, -C(O)R12, -C(O)OR12, -C(O)N(R?13)R12, -N(R13)C(O)R12¿, -OC(O)N(R?13)R12, -N(R13)C(O)OR12¿, -(CH¿2?)n4N(R?13¿)C(O)N(R13)R12, -OP(O)(OR13)OR12 or -C(O)N(R14)CH(COOH)R?12, or X9¿ is -N= or -N(R4)-, wherein R4 is -C(O)R12, -C(O)OR12, -C(O)N(R13)R12, -OC(O)N(R13)R12 or -C(O)N(R14)CH(COOH)R12, wherein R?12, R13 and R14¿ are as defined in the Summary of the Invention; R5 is hydrogen or (C¿1-4?)alkyl, R?6¿ is hydrogen or (C¿1-4¿) alkyl, which alkyl optionally is substituted with one to two substituents independently selected from (C¿1-4?)alkyloxy, hydroxy and sulfo, R?7¿ is hydrogen or methyl and R8 is hydrogen, methyl or hydroxy. The compounds, compositions and methods are effective for the prevention and treatment of inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis, as well as other types of immunomediated inflammatory disorders, such as rheumatoid arthritis, conjunctivitis and inflammatory bowel disease, various dermatological conditions, as well as certain viral conditions. The compounds comprise potent and selective inhibitors of the mast cell protease tryptase. The compositions for treating these conditions include oral, inhalant, topical and parenteral preparations as well as devices comprising such preparations.

公开(公告)号：EP1324993A2

公开(公告)日：2003-07-09

申请号：EP01969044.5

申请日：2001-04-18

申请人： Cytovia, Inc. ,  AXYS PHARMACEUTICALS, INC.

发明人： CAI, Sui, Xiong ,  DREWE, John, A. ,  SHELTON, Emma, Jane ,  LITVAK, Joane ,  SPERANDIO, David ,  SPENCER, Jeffrey, R.

IPC分类号： C07D281/06 ,  C07D281/10 ,  C07D417/04 ,  C07D417/14 ,  C07D513/04 ,  C07D513/14 ,  C07D405/04 ,  A61K31/55 ,  A61P35/00

CPC分类号： C07D417/14 ,  C07D281/06 ,  C07D281/10 ,  C07D405/04 ,  C07D417/04 ,  C07D513/04 ,  C07D513/14

摘要： The present invention is directed to substituted 1,4-thiazepine and analogs thereof, represented by the general Formula (I): wherein the dashed lines, A?1, A2, A3, X1 and R1¿ are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of capases and inducers of apoptosis. Therefore, the activators of caspases and inducers of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.