[EN] PYRAZOLE DERIVATIVES AS PROTEIN KINASE MODULATORS<br/>[FR] DERIVES DE PYRAZOLE SERVANT DE MODULATEURS DE PROTEINE KINASE
申请人:ASTEX TECHNOLOGY LTD
公开号:WO2005061463A1
公开(公告)日:2005-07-07
The invention provides compounds of the formula: (I) having protein kinase B inhibiting activity: wherein A is a saturated hydrocarbon linker group containing from 1 to 7 carbon atoms, the linker group having a maximum chain length of 5 atoms extending between Rl and NR2R3 and a maximum chain length of 4 atoms extending between E and NR2R3, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the inker group A may optionally bear one or more substituents selected from oxo, fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the NR2R3 group and provided that the oxo group when present is located at a carbon atom a with respect to the NR2R3 group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; Rl is an aryl or heteroaryl group; and R2, R3, R4 and R5 are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anticancer agents.
该发明提供了具有蛋白激酶B抑制活性的化合物,其化学式为:(I),其中A是一个饱和的含有1至7个碳原子的烷基链连接基团,该连接基团在R1和NR2R3之间延伸的最大链长为5个原子,在E和NR2R3之间延伸的最大链长为4个原子,其中连接基团中的一个碳原子可以选择性地被氧原子或氮原子取代;连接基团A的碳原子可以选择性地携带来自酮基、氟和羟基的一个或多个取代基,前提是当存在羟基时,该羟基不位于相对于NR2R3基团的碳原子a处,且当存在酮基时,该酮基位于相对于NR2R3基团的碳原子a处;E是一个单环或双环的碳环或杂环基团;R1是芳基或杂芳基团;R2、R3、R4和R5如权利要求中所定义。还提供了含有这些化合物的药物组合物,制备这些化合物的方法以及它们作为抗癌剂的用途。