公开(公告)号：EP1923386A3

公开(公告)日：2008-05-28

申请号：EP08001070.5

申请日：2001-03-29

申请人： Vertex Pharmceuticals Incorporated

发明人： Charrier, Jean-Damien ,  Bebbington, David ,  Kay, David ,  Knegtel, Ronald ,  Golec, Julian ,  Mortimore, Michael ,  Studley, John

IPC分类号： C07D209/86 ,  A61K31/395 ,  A61P43/00 ,  C07D209/88 ,  C07D209/08 ,  C07D279/30 ,  C07D221/12 ,  C07D223/22 ,  C07D403/12

CPC分类号： C07D209/08 ,  C07D209/86 ,  C07D221/12 ,  C07D223/26 ,  C07D223/28 ,  C07D279/30 ,  C07D403/12

摘要： This invention provides caspase inhibitors of formula (I): wherein Z is oxygen or sulfur; R is hydrogen, -CHN2,R, CH2OR, CH2SR, or -CH2Y; Y is an electronegative leaving group; R is CO2H, CH2CO2H, or esters, amides or isosteres thereof; R is a group capable of fitting into the S2 subsite of a caspase enzyme; R and R are taken together with the intervening nitrogen to form heterocyclic ring and R is as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1 beta secretion.

公开(公告)号：EP2083014A3

公开(公告)日：2010-01-06

申请号：EP09004786.1

申请日：1996-12-26

申请人： Vertex Pharmceuticals Incorporated

发明人： Batchelor, Mark J. ,  Bebbington, David ,  Bemis, Guy, W. ,  Fridman, Wolf, Herman ,  Gillespie, Roger, J. ,  Golec, Julian M. C. ,  Gu, Yong ,  Laufer, David J. ,  Livingston, David J. ,  Matharu, Saroop S. ,  Mullican, Michael D. ,  Murcko, Mark A. ,  Murdoch, Robert ,  Nyce, Philip L. ,  Robidoux, Andrea L. ,  Su, Michael ,  Wannamaker, M. Woods ,  Wilson, Keith P. ,  Zelle, Robert E.

IPC分类号： C07K5/023 ,  C07D487/04 ,  A61K38/04 ,  A61K31/55 ,  C07D243/00 ,  C07D237/00

CPC分类号： C07D243/12 ,  A61K38/00 ,  C07D401/06 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07K5/0202 ,  C07K5/06139 ,  C07K5/0821

摘要： The present invention relates to novel classes of compounds which are inhibitors of interleukin-1β converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physiochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against IL-1-, apoptosis-, IGIF-, and IFN-γ-mediated diseases, inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, degenerative diseases, and necrotic diseases. This invention also relates to methods for inhibiting ICE activity, for treating interleukin-1-, apoptosis-, IGIF-, and IFN-γ-mediated diseases and decreasing IGIF, and IFN-γ production using the compounds and compositions of this invention. This invention also relates to methods for preparing N-acylamino compounds.

公开(公告)号：EP2083014A2

公开(公告)日：2009-07-29

申请号：EP09004786.1

申请日：1996-12-26

申请人： Vertex Pharmceuticals Incorporated

发明人： Batchelor, Mark J. ,  Bebbington, David ,  Bemis, Guy, W. ,  Fridman, Wolf, Herman ,  Gillespie, Roger, J. ,  Golec, Julian M. C. ,  Gu, Yong ,  Laufer, David J. ,  Livingston, David J. ,  Matharu, Saroop S. ,  Mullican, Michael D. ,  Murcko, Mark A. ,  Murdoch, Robert ,  Nyce, Philip L. ,  Robidoux, Andrea L. ,  Su, Michael ,  Wannamaker, M. Woods ,  Wilson, Keith P. ,  Zelle, Robert E.

IPC分类号： C07K5/023 ,  C07D487/04 ,  C07D498/04 ,  A61K38/04 ,  A61K31/55 ,  C07D243/00 ,  C07D237/00

CPC分类号： C07D243/12 ,  A61K38/00 ,  C07D401/06 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07K5/0202 ,  C07K5/06139 ,  C07K5/0821

摘要： The present invention relates to novel classes of compounds which are inhibitors of interleukin-1β converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physiochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against IL-1-, apoptosis-, IGIF-, and IFN-γ-mediated diseases, inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, degenerative diseases, and necrotic diseases. This invention also relates to methods for inhibiting ICE activity, for treating interleukin-1-, apoptosis-, IGIF-, and IFN-γ-mediated diseases and decreasing IGIF, and IFN-γ production using the compounds and compositions of this invention. This invention also relates to methods for preparing N-acylamino compounds.

摘要翻译： 本发明涉及作为白细胞介素-1转化酶抑制剂的新型化合物。 本发明的ICE抑制剂的特征在于具体的结构和生理化学特征。 本发明还涉及包含这些化合物的药物组合物。 本发明的化合物和药物组合物特别适合于抑制ICE活性，因此可有利地用作抗IL-1，细胞凋亡，IGIF和IFN-3介导的疾病，炎性疾病，自身免疫疾病 ，破坏性骨病，增殖性疾病，感染性疾病，退行性疾病和坏死性疾病。 本发明还涉及使用本发明的化合物和组合物来抑制ICE活性，用于治疗白介素-1-，细胞凋亡，IGIF和IFN-3介导的疾病并减少IGIF和IFN-3产生的方法。 本发明还涉及制备N-酰基氨基化合物的方法。

公开(公告)号：EP1923386A2

公开(公告)日：2008-05-21

申请号：EP08001070.5

申请日：2001-03-29

申请人： Vertex Pharmceuticals Incorporated

发明人： Charrier, Jean-Damien ,  Bebbington, David ,  Kay, David ,  Knegtel, Ronald ,  Golec, Julian ,  Mortimore, Michael ,  Studley, John

IPC分类号： C07D209/86 ,  A61K31/395 ,  A61P43/00 ,  C07D209/88 ,  C07D209/08 ,  C07D279/30 ,  C07D221/12 ,  C07D223/22 ,  C07D403/12

CPC分类号： C07D209/08 ,  C07D209/86 ,  C07D221/12 ,  C07D223/26 ,  C07D223/28 ,  C07D279/30 ,  C07D403/12

摘要： This invention provides caspase inhibitors of formula (I): wherein Z is oxygen or sulfur; R is hydrogen, -CHN2,R, CH2OR, CH2SR, or -CH2Y; Y is an electronegative leaving group; R is CO2H, CH2CO2H, or esters, amides or isosteres thereof; R is a group capable of fitting into the S2 subsite of a caspase enzyme; R and R are taken together with the intervening nitrogen to form heterocyclic ring and R is as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1 beta secretion.

摘要翻译： 本发明提供式（I）的半胱天冬酶抑制剂：其中Z是氧或硫; R 1是氢，-CHN 2，R，CH 2 OR，CH 2 SR或-CH 2 Y; Y是一个负电离群体; R 2是CO 2 H，CH 2 CO 2 H或其酯，酰胺或等排物; R 3是能够进入半胱天冬酶的S2亚位点的基团; R 4和R 5与插入的氮一起形成杂环并且R如说明书中所述。 这些化合物是细胞凋亡和IL-1β分泌的有效抑制剂。