呋喃并[3,2-g]色满类化合物的合成及抗肿瘤活性研究  

Synthesis and Antitumor Activities of Furo[3,2-g]chroman Derivatives

作　　者：徐晶 丁宁[1] 冯健 谢倩 焦思蒙 王世辉[1] 刘晓平[1] 胡春[1] XU Jing;DING Ning;FENG Jian;XIE Qian;JIAO Si-meng;WANG Shi-hui;LIU Xiao-ping;HU Chun(Key Laboratory of Structure-Based Drug Design&Discovery,Ministry of Education,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学“基于靶点的药物设计与研究”教育部重点实验室,辽宁沈阳110016

出　　处：《精细化工中间体》2020年第1期23-28,54,共7页Fine Chemical Intermediates

基　　金：国家自然科学基金项目(21342006)。

摘　　要：为了发现新型选择性雌激素受体调节剂,以雷洛昔芬为先导化合物,利用生物电子等排原理以及拼合原理,将雷洛昔芬结构中的苯并噻吩环替换成呋喃并[3,2-g]色满骨架,并进行结构优化,考虑到目标化合物合成的可行性等因素,设计出2-芳酰基-3-芳基呋喃并[3,2-g]色满类化合物作为目标化合物。以7-羟基色满为原料,经过酯化反应和Fries重排后得到6-(4-甲氧基苯甲酰基)-7-羟基色满,进而与取代的α-卤代苯乙酮缩合得关键中间体2-芳甲酰基-3-(4-甲氧基苯基)呋喃并[3,2-g]色满,脱甲基后再与不同氯乙基胺类化合物进行Williamson反应得到目标化合物。所有的10个目标化合物均未见文献报道,其结构经ESI-MS和1H NMR确证。采用MTT法对目标化合物体外抗肿瘤活性进行初步筛选,结果表明,目标化合物7d对人乳腺癌细胞MCF-7、人骨肉瘤细胞U2OS-EGFP-4A12G和人卵巢癌细胞SKOV3具有显著的抑制活性,具有进一步研究价值。In order to discover a novel selective estrogen receptor modulator,taking raloxifene as the lead compound,based on the principles of bioisosterism and hypridization,replacing the benzothiophene ring in raloxifene with furano[3,2-g]chroman scaffold,combining the feasibility of synthesis of the target compounds,a novel series of 2-aroyl-3-arylfuro[3,2-g]chroman were designed as the target compounds.The 6-(4-methoxybenzoyl)-7-hydroxychroman was obtained from 7-hydroxychroman by esterification and Fries rearrangement,and was converted to the key intermediates 2-aroyl-3-(4-methoxyphenyl)furo[3,2-g]chroman derivatives by condensation with substitutedα-haloacetophenones.Some target compounds were obtained the demethylations of the key intermediates,and the other target compounds were yielded by Williamson reaction with different chloroethylamines.All the 10 target compounds were not reported in literature,and their structures were confirmed by ESI-MS and1 H NMR.The antitumor activities of the target compounds in vitro were evaluated by MTT assay.The screening results showed that the target compound 7 d had potent inhibitory activities against human breast cancer cell MCF-7,human osteosarcoma cell U2 OS-EGFP-4 A12 G and human ovarian cancer cell SKOV3,and would be further research in the future.

关 键 词：选择性雌激素受体调节剂 呋喃并[3 2-g]色满 合成 表征 抗肿瘤活性 

分 类 号：R979.1[医药卫生—药品]