VEGF受体酪氨酸激酶抑制剂苯胺酞嗪类化合物的设计及合成研究

【作者】 黄亮；

【导师】 宫平；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2005， 硕士

【摘要】 本文是关于一类新型的血管内皮细胞生长因子(VEGF)受体酪氨酸激酶抑制剂——苯胺酞嗪类化合物的设计及合成研究。本文简述了血管生长抑制剂的发展概况及作用机理，详细介绍了VEGF受体酪氨酸激酶抑制剂的研究进展，重点研究了该类化合物的路线设计及合成。以PTK787为先导化合物，在保留其活性酞嗪母环结构的基础上，对母环1位和4位进行结构修饰，设计了一系列4位接各种取代苯(苄)硫甲基的苯胺酞嗪类化合物。设计并打通了全新的合成路线，以邻苯二甲酸酐和丙二酸为起始原料，经缩合、甲基化、溴代、取代、环合、氯代、胺解及单氧化和双氧化共七到九步反应，共制得34个未见文献报道的目标化合物。目标化合物结构经核磁共振氢谱、质谱及红外光谱得以确证。目标化合物的药理活性测试正在进行中。更多还原

【Abstract】 In this thesis the design and synthesis of a new type of VEGF receptor kinase inhibitors, anilinophthalazine, were studied.The development and action mechanism of angiogenesis inhibitors were introduced briefly and the inhibitors of VEGF receptor tyrosine kinases (RTKs) were described in detail in the paper. The design and synthesis of anilinophthalazine derivatives were researched particularly. Based on the analysis of structure-activity relationship (SAR) of anilinophthalazine derivatives, taking PTK787 as lead compound, some modifications were made at the 1 and 4 positions preserving such structures as phthalazine nucleus. With phthalic anhydride and malonate as starting materials, a new synthetic scheme was developed and thirty-four new compounds which had not been reported in literatures were synthesized. The structures of the target compounds were confirmed by ~1H-NMR、MS and IR.The pharmacological evaluation of these target compounds is in process.更多还原