目的 對合成的一系列凡德他尼衍生物進(jìn)行體內(nèi)外抗腫瘤活性的篩選，為尋找低毒高效的新型酪氨酸激酶抑制劑研究提供依據(jù)。方法 體外篩選采用均相時(shí)間分辨熒光（HTRF）法和磺酰羅丹明B（SRB）法分別進(jìn)行激酶和細(xì)胞的篩選；采用經(jīng)典的急性毒性實(shí)驗(yàn)方法，并建立移植人非小細(xì)胞肺癌H1975裸鼠模型評價(jià)其抗腫瘤活性。結(jié)果 HTRF結(jié)果顯示有6個活性較好的化合物（TY8115、TY8119、TY8122、TY8128、TY8129、TY8131），其中TY8115對VEGFR-2和EGFR抑制作用均好于凡德他尼；SRB結(jié)果顯示這些活性化合物對選用的3種靶細(xì)胞（A431、H1975、A549）均有不同程度的抑制作用，其中TY8115的腫瘤細(xì)胞增殖抑制作用最明顯，且對非靶細(xì)胞（MDA-MB-231）生長影響很?。患毙远拘詫?shí)驗(yàn)結(jié)果顯示TY8115沒有表現(xiàn)出毒性反應(yīng)；體內(nèi)抗腫瘤活性研究結(jié)果顯示TY8115對肺癌H1975具有療效，75、150 mg/kg TY8115對H1975的相對腫瘤增殖率分別為54.44%、39.54%。結(jié)論 化合物TY8115具有良好的抗腫瘤活性，并且毒副作用小，具有發(fā)展成為一種新型酪氨酸激酶抑制劑的潛力。

Objective To screen the antitumor activity in vivo and in vitro of the series of vandetanib derivatives, and to provide the basis for seeking new tyrosine kinase inhibitors with high efficiency and low toxicity. Methods Homogeneous time-resolved fluorescence (HTRF) and SRB method were used to screen kinases and cells in vitro; The acute toxicity experiment of classical methods was used, and nude mice model transplanted by non-small cell lung cancer H1975 cells was established to evaluate the antitumor activity. Results Six compounds (TY8115, TY8119, TY8122, TY8128, TY8129, and TY8131) with better activities were selected by HTRF method, where TY8115 had better inhibitory effect onVEGFR-2 and EGFR than vandetanib. The above active compounds showed different degrees of inhibition on three kinds of target cells (A431, H1975, and A549) by SRB method, and the inhibition of TY8115 was the most obvious. TY8115 had little impact on the non target cell (MDA-MB-231) growth. Results of acute toxicity test showed that TY8115 exhibited no toxicity. Antitumor activity in vivo showed that TY8115 with doses of 75 and 150 mg/kg had curative effect on lung cancer H1975 cells with relative tumor growth rates of 54.44% and 39.54%, respectively. Conclusion The compound TY8115 has good antitumor activity in vitro and in vivo, and has no previous toxicity, which will be an new tyrosine kinase inhibitor.