公开(公告)号：EP1322617A1

公开(公告)日：2003-07-02

申请号：EP01975252.6

申请日：2001-09-18

申请人： SIGNAL PHARMACEUTICALS, INC. ,  AXYS PHARMACEUTICALS, INC.

发明人： BHAGWAT, Shripad, S. ,  GAYO-FUNG, Leah, M. ,  STEIN, Bernd, M. ,  CHAO, Qi ,  GANGLOFF, Anthony, R. ,  MCKIE, Jeffrey, A. ,  RICE, Kenneth, D.

IPC分类号： C07D217/20 ,  C07D217/18 ,  C07D209/44 ,  C07D223/16 ,  C07D401/04 ,  C07D401/12 ,  C07D405/04 ,  C07D417/12 ,  C07D405/12 ,  C07D413/10 ,  C07D401/10 ,  C07D401/06 ,  A61K31/472 ,  A61P35/00

CPC分类号： C07D223/16 ,  C07D209/44 ,  C07D217/04 ,  C07D217/16 ,  C07D217/18 ,  C07D217/20 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D405/04 ,  C07D405/12 ,  C07D413/10 ,  C07D417/12

摘要： Compounds have the structure: including srereoisomers and pharmaceutically acceptable salts thereof; wherein a is 0, 1 or 2; A, B and C are independently CH, CR or N, wherein R is C1-6 alkyl; D is-(CH2)nC(=O)(CH2)m-; R1, R2, R3 are substituents modulate the estrogen receptor (ER) and methods for treating estrogen-related conditions, including conditions such as breast cancer, testicular cancer, osteoporosis, endometriosis, cardiovascular disease, hypercholesterolemia, prostatic hypertrophy, prostatic carcinomas, obesity, hot flashes, skin effects, mood swings, memory loss, urinary incontinence, hairloss, cataracts, natureal hormonal imbalances, and adverse reproductive effects associated with exposure to environmental chemicals.

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.