AIM:To develop the general route for the synthesis of gefitinib.METHOD: 2-Amino-4,5-dimethoxybenzoic acid was cyclized,monodemethylated,acetylated,ammoniated and chlorinated to obtain the target compound.RESULT:The st...AIM:To develop the general route for the synthesis of gefitinib.METHOD: 2-Amino-4,5-dimethoxybenzoic acid was cyclized,monodemethylated,acetylated,ammoniated and chlorinated to obtain the target compound.RESULT:The structure was confirmed by elemental analysis, IR and 1H NMR.CONCLUSION:Synthetic route and methods is feasible for the preparation of gefitinib.展开更多
文摘AIM:To develop the general route for the synthesis of gefitinib.METHOD: 2-Amino-4,5-dimethoxybenzoic acid was cyclized,monodemethylated,acetylated,ammoniated and chlorinated to obtain the target compound.RESULT:The structure was confirmed by elemental analysis, IR and 1H NMR.CONCLUSION:Synthetic route and methods is feasible for the preparation of gefitinib.
文摘目的 探究不同靶向药物对表皮生长因子受体(epithelial growth factor receptor, EGFR)表达异常的非小细胞肺癌放疗敏感性的影响及其作用机制。方法 选取EGFR过度表达的A549细胞系及EGFR突变的HCC827细胞系,随机均分为空白对照组、放疗组、吉非替尼组、尼妥珠单抗组、放疗+吉非替尼组、放疗+尼妥珠单抗组。尼妥珠单抗组、放疗+尼妥珠单抗组均加入100 μg/ml的尼妥珠单抗溶液,吉非替尼组、放疗+吉非替尼组均加入100 μl浓度为1 μmol/L的吉非替尼溶液,空白对照组及放疗组予以等量的PBS溶液,后放疗组、放疗+尼妥珠单抗组、放疗+吉非替尼组予直线加速器放射处理。利用MTT实验观察细胞增殖情况,采用克隆实验比较细胞放射敏感性,使用流式细胞术分析细胞周期及凋亡情况,采用Western blot检测EGFR、磷酸化EGFR(p-EGFR)及p-Akt表达水平。结果 与放疗组比较,放疗+吉非替尼组、放疗+尼妥珠单抗组能显著抑制A549细胞增殖,升高G0/G1期所占比例,提升细胞凋亡率,差异有统计学意义( P <0.05),而HCC827细胞则无明显改变( P >0.05);A549细胞、HCC827细胞的放疗+吉非替尼组、放疗+尼妥珠单抗组的放疗增敏系数显著高于放疗组( P <0.05);A549细胞放疗+吉非替尼组、放疗+尼妥珠单抗组EGFR、p-EGFR及p-Akt表达水平较放疗组显著降低( P <0.05),但HCC827细胞则无明显改变( P >0.05)。结论 吉非替尼及尼妥珠单抗联合放疗可阻滞A549细胞于G0/G1期,下调EGFR、p-EGFR及p-Akt表达水平,增加细胞放疗敏感性,而对HCC827细胞则无明显影响。
