5-氨基-1,3-二氢-1,3-二氧-异吲哚-2-丙酸类衍生物的合成及抗血管生成活性研究有机化学.pdfVIP

2007 年第 27 卷 有 机 化 学 Vol. 27, 2007 第 9 期, 1110～1115 Chinese Journal of Organic Chemistry No. 9, 1110～1115 ·研究论文· 5-氨基-1,3-二氢-1,3-二氧-异吲哚-2-丙酸类衍生物的合成及 抗血管生成活性研究 吴 贝 a 杨大成 b 沈 怡 a 邓 勇*,a 钟裕国 a (a 四川大学华西药学院靶向药物教育部重点实验室 成都 610041) (b 西南大学化学化工学院 重庆 400715) 摘要 根据 RGD 序列肽的构效关系, 设计并合成了一系列以 5-氨基-1,3-二氢-1,3-二氧-异吲哚-2-丙酸为分子骨架的新 化合物. 其中间体和目标物的化学结构经 1H NMR, MS 和元素分析确证. 体外初步生物活性筛选结果表明, 目标物在 10－5 mol/L 浓度下对 bFGF 诱导的鸡胚绒毛尿囊膜新生血管生成有显著抑制活性. 关键词 RGD 序列肽; 5-氨基-1,3-二氢-1,3-二氧-异吲哚衍生物; 合成; 抗新生血管生成 Synthesis of 5-Amino-1,3-dihydro-1,3-dioxo-isoindole-2-propanoic Acid Derivatives and Their Antiangiogenic Activities WU, Beia YANG, Da-Chengb SHEN, Yia DENG, Yong*,a ZHONG, Yu-Guoa a ( Key Laboratory of Drug Targeting, Ministry of Education , West China School of Pharmacy, Sichuan University, Chengdu 610041) (b School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715) Abstract Based on the structure-activity relationships of RGD-containing peptides, a series of novel 5-amino-1,3-dihydro-1,3-dioxo-isoindole derivatives were designed and synthesized. The intermediates and 1 target compounds were characterized by H NMR, MS spectra and elemental analysis. Their ability to inhibit angiogenesis was evaluated in the chick embryo chorioallantoic membrane assay at 10－5 mol/L. Some com- pounds displayed obviously