Nitrostyrene Derivatives of Adenosine 5′-Glutarates Modified with an Alkyl Spacer and their inhibitory activity on epidermal growth factor receptor protein tyrosine kinase
作者:Stefan Peterli、Dieter Hubmann、Urs Séquin、Helmut Mett、Peter Traxler
DOI:10.1002/hlca.19940770109
日期:1994.2.9
β-Nitrostyrene derivatives of adenosine 5′-glutarates are potent and selective bisubstrate-type inhibitors of the epidermal growth factor receptor protein tyrosine kinase (EGF-R PTK). In an attempt to improve the inhibitory activity, this type of compounds was modified with alkyl spacers of varying length between the nitrostyrene and the glutaryl units. The spacers consisted of 1, 3, 4, and 5 atoms to give
腺苷5'-戊二酸的β-硝基苯乙烯衍生物是表皮生长因子受体蛋白酪氨酸激酶(EGF-R PTK)的有效且选择性的双底物型抑制剂。为了改善抑制活性,用在硝基苯乙烯和戊二烯基单元之间变化长度的烷基间隔基修饰了这类化合物。间隔基由1、3、4和5个原子组成,分别得到苄基,氧乙基,氧丙基和氧丁基系列的化合物(方案1和2)。仅以苄基和氧丙基系列制备腺苷5'-酯。与不带间隔子的母体系列化合物(IC 50 = 0.7–12μM)相比,大多数修饰的化合物仅少量或无活性地抑制了EGF-R PTK(IC 50 ≥100μM)。唯一的例外是游离酸19和20,IC 50值为ca。5微米 值得注意的是,这两个戊二酸氢盐与MeOH或腺苷的酯化反应会生成无活性的化合物,这与没有间隔基的相应物质形成对比。