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：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。