SU11274衍生物的合成及受体酪氨酸激酶抑制活性评价  

Synthesis and Biochemical Evaluation of Receptor Tyrosine Kinase Inhibitory Activity of SU11274 Analogs

作　　者：徐培培[1] 颜海燕[1] 张首国[1] 刘靖[1] 温晓雪[1] 彭涛[1] 徐琪寿[1] 王林[1] 

机构地区：[1]军事医学科学院放射与辐射医学研究所,北京100850

出　　处：《解放军药学学报》2011年第3期193-196,共4页Pharmaceutical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金;No.81072531

摘　　要：目的合成SU11274衍生物并对其进行受体PTK抑制活性评价。方法合成了用乙二胺、1,3-丙二胺、1,2-丙二胺、1,6-己二胺替代SU11274哌嗪基团的4个SU11274新衍生物,结构经1H-NMR和ESI-MS验证。采用ELISA方法对这4个化合物进行了受体PTK抑制活性评价。结果合成的4个SU11274衍生物(5a,5b,5c,5d)均为新化合物。生物学评价结果显示化合物5b的受体PTK抑制活性要显著优于SU11274,化合物5c有非常显著的受体PTK抑制活性,而5a和5d则较弱。结论 SU11274的哌嗪基团被不同二胺取代会影响化合物的受体PTK抑制活性。Objective To synthesize and evaluate the inhibition of SU11274 analogs on the receptor tyrosine kinase.Methods Four new SU11274 analogs with 1,2-diaminoethane,1,3-diaminopropane,1,2-diaminopropane and 1,6-diaminohexane substituting the SU11274 piperazine group were synthesized.Their structures were verified by 1H-NMR and ESI-MS.The receptor tyrosine kinase inhibitiory activity was studied by ELISA assay.Results Four SU11274 analogs were new compounds.Biochemical evaluations demonstrate that receptor tyrosine kinase inhibitory activity of 5b was significantly better than that of SU11274,but that of compound 5c was the most significant.The inhibitory activities of 5a and 5b was very low.Conclusion Substitution of the piperazine of SU11274 with different side chains affects the inhibitory activity of receptor tyrosine kinase of SU11274 analogs.

关 键 词：SU11274衍生物 合成 受体酪氨酸激酶 抑制活性 

分 类 号：R962[医药卫生—药理学]