公开(公告)号：US07351702B2

公开(公告)日：2008-04-01

申请号：US10153971

申请日：2002-05-23

申请人： Michael Mortimore ,  Andrew Miller ,  John Studley ,  Jean-Damien Charrier

发明人： Michael Mortimore ,  Andrew Miller ,  John Studley ,  Jean-Damien Charrier

IPC分类号： A01N31/55 ,  A61K31/55

CPC分类号： A61K31/55 ,  A61K31/4015 ,  A61K31/403 ,  A61K31/407 ,  A61K31/435 ,  A61K31/45 ,  A61K31/498 ,  A61K31/5025 ,  A61K31/538 ,  A61K31/54 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/389

摘要： This invention provides compounds of formula I: wherein Z is oxygen or sulfur; R1 is hydrogen, —CHN2, R, CH2OR, CH2SR, or —CH2Y; next to R3 represents a single or double bond; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; R3 is a group capable of fitting into the S2 subsite of a caspase enzyme; R4 is a hydrogen or C1-6 alkyl or R3 and R4 taken together form a ring; Ring A and Ring B are each heterocyclic rings, and R and R5 are as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1β secretion.

摘要翻译： 本发明提供式I化合物：其中Z是氧或硫; R 1是氢，-CHN 2，R 2，CH 2 OR，CH 2 SR或-CH 2 Y; “img id =”CUSTOM-CHARACTER-00001“he =”1.78mm“wi =”6.01mm“file =”US07351702-20080401-P00001.TIF“alt =”custom character“img-content =”character“img-format =“tif”/> R 3旁边代表单键或双键; Y是电负离子团; R 2是CO 2 H，CH 2 CO 2 H，或它们的酯，酰胺或等体醇; R 3是能够适应半胱天冬酶的S2亚位点的基团; R 4是氢或C 1-6烷基或R 3和R 4合在一起形成环 ; 环A和环B各自是杂环，R和R 5如说明书中所述。 这些化合物是凋亡和IL-1β分泌的有效抑制剂。