CN108117516B - 一种多取代吡啶衍生物的制备方法及其应用 - Google Patents

一种多取代吡啶衍生物的制备方法及其应用 Download PDF

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CN108117516B
CN108117516B CN201711494476.5A CN201711494476A CN108117516B CN 108117516 B CN108117516 B CN 108117516B CN 201711494476 A CN201711494476 A CN 201711494476A CN 108117516 B CN108117516 B CN 108117516B
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凌飞
肖莲
钟为慧
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Zhejiang University of Technology ZJUT
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Abstract

本发明公开了一种多取代吡啶衍生物的制备方法及其应用。本方法将烯胺酯类化合物、酮类化合物、催化剂和氧化剂溶于有机溶剂,在催化剂和氧化剂的作用下,烯胺酯类化合物和酮类化合物经氧化环合生成多取代吡啶衍生物。本发明的制备方法反应原料简单易得,实验操作简单,反应条件相对温和;反应活性高,通过高度的化学选择性和区域选择性构建不同取代基的多取代吡啶衍生物,有利于进行下一步的衍生化研究。且所获得的多取代吡啶衍生物对人肺癌细胞A‑549和人肝癌细胞HepG‑2具有潜在的抑制活性。本发明提供的吡啶衍生物(Ⅰ)和(Ⅱ)具有潜在的体外抗肿瘤细胞活性,具有开发成抗肿瘤药的前景。

Description

一种多取代吡啶衍生物的制备方法及其应用
技术领域
本发明属于医药化工中间体合成技术领域,具体涉及一种多取代吡啶衍生物的制备方法及其应用。
背景技术
多取代吡啶衍生物是一类重要的杂环化合物,在医药、农业、化工、纺染等领域均有应用。特别是其中一类吡啶衍生物-烟酸酯,其水解产物烟酸属于维生素B族化合物,具有扩张周围血管的作用。该类多取代吡啶衍生物经结构修饰可制备多种药物,例如目前默沙东研发的MK-1064,主治失眠症,正处于临床一期实验阶段。MK-1064可由2,5位含吡啶基取代的烟酸酯经胺解得到。其结构式如下:
Figure GDA0001635428920000011
由于多取代吡啶衍生物具有特殊的生物和药理活性,因此众多学者专注于该类化合物的合成方法研究。其中最经典的方法为Hantzsch反应(Justus Liebigs Ann.Chem.,1882,215(1),1-82.),两分子β-羰基酸酯与一分子醛及一分子氨发生缩合反应,再用氧化剂氧化得到对称的3,5-二羧酸酯吡啶衍生物。Hantzsch反应存在着反应时间长、操作复杂、收率低且产物结构单一等缺点。
另一类方法是以烯胺酯类化合物为基本底物,与1,3-二酮化合物(Chem.Pharm.Bull.1975,23,2239-2250.)、α,β-不饱和酮(Chem.Commun.2017,53,2390-2393)、炔酮(Synlett 2001,1149-1151)、烯丙醇(Chem.Commun.2013,49,7926-7928)等反应合成吡啶衍生物。该类方法存在反应条件苛刻(高温、微波、使用有爆炸风险的强氧化剂2-碘酰基苯甲酸(IBX)等)、起始原料不易得、实验操作复杂等缺点。因此,设计一种操作简单、原料易得、选择性高的多取代吡啶衍生物的合成方法值得探究。
发明内容
针对现有技术中存在的上述问题,本发明的目的在于提供一种多取代吡啶衍生物的制备方法及其应用,使用简单易得的原料制备一系列多取代吡啶衍生物。
所述的一种多取代吡啶衍生物的制备方法,其特征在于所述的制备方法为:将式(Ⅲ)或式(Ⅴ)所示的烯胺酯类化合物、式(Ⅳ)所示的酮类化合物、催化剂和氧化剂溶于有机溶剂中,在110~150℃温度下反应15~30小时,反应结束后,反应液萃取、浓缩后经柱层析分离,得到式(Ⅰ)或(Ⅱ)所示的多取代吡啶衍生物;
多取代吡啶衍生物的结构式下所示:
Figure GDA0001635428920000021
烯胺酯类化合物结构式如下所示:
Figure GDA0001635428920000031
酮类化合物结构式如Ⅳ所示:
Figure GDA0001635428920000032
其中,R1为烷基、芳基或杂芳基,R2为烷基,R3为烷基、芳基或氢,R4为烷基、芳基或杂芳基;R5为氢、烷基或卤素。
所述的多取代吡啶衍生物的制备方法,其特征在于R1、R2、R3、R4选自甲基、乙基、叔丁基、苯、取代苯、萘、噻吩、吡啶、呋喃,取代苯的取代基选自H、CH3O-、CH3-、F、Cl、Br、CF3-、NO2-,R1优选为苯基或噻吩,R2优选为甲基、乙基或叔丁基,R3优选为氢或萘,R4优选为苯基、对溴苯基、对氟苯基、对甲基苯基、对氧甲基苯基或对三氟甲基苯基,R5优选为氢。
所述的多取代吡啶衍生物的制备方法,其特征在于催化剂为醋酸铜、醋酸亚铜、三氟甲烷磺酸铜、氯化铜、溴化铜、碘化铜、氯化亚铜、溴化亚铜、碘化亚铜、醋酸钯、氯化铁中的一种;催化剂的用量为5~20mol%,优选为8~15mol%。
所述的多取代吡啶衍生物的制备方法,其特征在于氧化剂为四甲基哌啶(TEMPO)或氮氧自由基哌啶醇(4-OH-TEMPO)。
所述的多取代吡啶衍生物的制备方法,其特征在于烯胺酯类化合物和酮类化合物的物质的量比为1:1~4,优选为1:1~2。
所述的多取代吡啶衍生物的制备方法,其特征在于有机溶剂为氯苯、甲苯、乙腈、二甲基亚砜、1,2-二氯苯、N,N-二甲基甲酰胺、异丙基苯、二氧六环、1,2-二氯乙烷中的一种。
所述的多取代吡啶衍生物的制备方法,其特征在于催化剂的配体为2,2'-联吡啶(bpy)、四甲基乙二胺(TMEDA)、邻二氮菲(1,10-Phen)中的一种。
本发明的反应方程式如下所示:
Figure GDA0001635428920000041
本发明的另一目的是提供所述的多取代吡啶衍生物的制备方法在制备抗肿瘤药物中的应用。
进一步,所述的多取代吡啶衍生物应用于制备抗肺癌或肝癌药物。
初步的药理实验发现,本发明提供的化合物对A549、HepG-2等肿瘤细胞株均有很好的体外抑制增殖作用,可应用于制备抗肺癌或肝癌药物,所述的吡啶衍生物为下列式Ⅰa、Ⅰb、Ⅰc、Ⅰd、Ⅰe、Ⅰf、Ⅱa、Ⅱb、Ⅱc、Ⅱd之一。
Figure GDA0001635428920000042
Figure GDA0001635428920000051
其中化合物Ⅱc、Ⅱd对人肝癌细胞的抑制率较突出,其IC50值达到4.11μM和3.47μM。
与现有技术相比,本发明的有益效果主要体现在:
本发明的制备方法所用的反应原料简单易得,实验操作简单,反应条件相对温和;反应活性高,通过高度的化学选择性和区域选择性构建不同取代基的多取代吡啶衍生物,有利于进行下一步的衍生化研究。所合成的吡啶衍生物(Ⅰ)和(Ⅱ)结构新颖,初步的药理活性实验表明该类化合物对人肺癌细胞A-549和人肝癌细胞HepG-2具有潜在的抑制活性。
具体实施方式
下面结合具体实施例对本发明进行进一步描述,但不仅限于本发明所列出的具体实施例描述的实施方案。
实施例1:6-(4-溴苯基)-2-苯基烟酸乙酯(Ⅰa)的制备
将3-氨基-3-苯基丙烯酸乙酯(0.96g,5mmol)、对溴苯丙酮(1.28g,6mmol)、醋酸铜(0.18g,1mmol)、bpy(0.31g,2mmol)和4-OH-TEMPO(0.86g,5mmol)的甲苯(10mL)溶液在120℃下搅拌反应24小时,反应结束后,用水和乙酸乙酯萃取,有机相用无水硫酸钠干燥,浓缩,用石油醚/乙酸乙酯=50/1(V/V)混合溶剂作洗脱剂,经硅胶柱层析分离得到白色固体6-(4-溴苯基)-2-苯基烟酸乙酯(Ⅰa)1.59g,收率:83%,熔点:59~60℃。
Ⅰa结构式为:
Figure GDA0001635428920000061
1H NMR(600MHz,CDCl3,ppm)δ8.18(d,J=7.8Hz,1H),8.01(d,J=8.4Hz,2H),7.75(d,J=7.8Hz,1H),7.63-7.60(m,4H),7.46(m,3H),4.17(q,J=7.2Hz,2H),1.07(t,J=7.2Hz,3H).13C NMR(150MHz,CDCl3,ppm)δ168.2,158.9,157.2,140.3,1391,137.14,132.0,129.0,128.8,128.7,128.1,125.7,124.4,117.6,61.5,13.7.HRMS(ESI-TOF)calcd forC20H16BrNNaO2[M+Na]+:404.0237;Found:404.0257.
实施例2:6-(4-溴苯基)-2-(2-噻吩基)烟酸乙酯(Ⅰb)的制备
将3-氨基-3-(2-噻吩基)烯酸乙酯(0.91g,5mmol)、对溴苯丙酮(1.07g,5mmol)、醋酸铜(0.18g,1mmol)、bpy(0.16g,1mmol)和4-OH-TEMPO(1.29g,7.5mmol)的甲苯(10mL)溶液在110℃下搅拌反应30小时,反应结束后,用水和乙酸乙酯萃取,有机相用无水硫酸钠干燥,浓缩,用石油醚/乙酸乙酯=50/1(V/V)混合溶剂作洗脱剂,经硅胶柱层析分离得到白色固体6-(4-溴苯基)-2-(2-噻吩基)烟酸乙酯(Ⅰb)1.30g,收率:70%。熔点:65.5~66.2℃。
Ⅰb结构式为:
Figure GDA0001635428920000071
1H NMR(600MHz,CDCl3,ppm)δ8.03-8.01(m,3H),7.66-7.63(m,3H),7.50-7.48(m,2H),7.13-7.11(m,1H),4.40(q,J=7.2Hz,2H),1.34(t,J=7.2Hz,3H).13C NMR(150MHz,CDCl3,ppm)δ168.3,156.7,150.5,143.2,138.7,136.7,132.0,128.7,128.7,128.0,127.7,124.5,124.3,117.0,61.9,14.0.HRMS(ESI-TOF)calcd for C18H14BrNNaO2S[M+Na]+:409.9814;Found:409.9821.
实施例3:6-(4-溴苯基)-2-苯甲基烟酸叔丁酯(Ⅰc)的制备
将3-氨基-3-苯基丙烯酸叔丁酯(1.10g,5mmol)、对溴苯丙酮(3.20g,15mmol)、醋酸铜(0.18g,1mmol)、1,10-Phen(0.20g,1mmol)和TEMPO(5mmol,0.78g)的甲苯(10mL)溶液在130℃下搅拌反应20小时,反应结束后,用水和乙酸乙酯萃取,有机相用无水硫酸钠干燥,浓缩,用石油醚/乙酸乙酯=50/1(V/V)混合溶剂作洗脱剂,经硅胶柱层析分离得到白色固体6-(4-溴苯基)-2-苯甲基烟酸叔丁酯(Ⅰc)1.01g,收率:49%。
Ⅰc结构式为:
Figure GDA0001635428920000081
1H NMR(600MHz,CDCl3,ppm)δ8.19(d,J=7.8Hz,1H),8.02(d,J=9.0Hz,2H),7.75(d,J=8.4Hz,1H),7.53(dd,J=7.8,1.8Hz,2H)7.63(d,J=9.0Hz,2H),7.51-7.46(m,3H),1.35(s,9H).13C NMR(150MHz,CDCl3,ppm)δ167.3,158.7,156.8,140.8,139.0,137.3,131.9,129.0,128.8,128.6,128.0,127.3,124.2,117.6,82.2,27.6.HRMS(ESI-TOF)calcdfor C22H20BrNNaO2[M+Na]+:432.0549;Found:432.0570.
实施例4:2,6-二苯基4-萘基烟酸乙酯(Ⅰd)的制备
将3-氨基-3-苯基丙烯酸乙酯(0.56g,5mmol)、对1-苯基-3-萘基丙酮(1.56g,6mmol)、醋酸铜(0.18g,1mmol)、1,10-Phen(0.20g,1mmol)和4-OH-TEMPO(0.86g,5mmol)的氯苯(10mL)溶液在150℃下搅拌反应18小时,反应结束后,用水和乙酸乙酯萃取,有机相用无水硫酸钠干燥,浓缩,用石油醚/乙酸乙酯=50/1(V/V)混合溶剂作洗脱剂,经硅胶柱层析分离得到白色固体2,6-二苯基4-萘基烟酸乙酯(Ⅰd)1.42g,收率:33%,熔点:53~55℃。
Ⅰd结构式为:
Figure GDA0001635428920000082
1H NMR(600MHz,CDCl3,ppm)δ8.21-8.19(m,2H),7.98(m,2H),7.89(m,2H),7.82(s,1H),7.76(d,J=8.5Hz,1H),7.59-7.47(m,10H),3.77(q,J=7.0Hz,2H),0.58(t,J=7.0Hz,3H).13C NMR(150MHz,CDCl3,ppm)δ168.2,156.8,156.8,148.8,140.1,138.4,136.0,133.5,131.4,129.6,128.9,128.8,128.8,128.3,128.3,128.1,127.3,126.5,126.5,126.2,125.9,125.0,120.4,61.1,13.1.HRMS(ESI-TOF)calcd for C30H23NNaO2[M+Na]+:452.1599;Found:452.1621.
实施例5:6-(4-溴苯基)-2-甲基烟酸甲酯(Ⅰe)的制备
将3-氨基-2-丁烯酸甲酯(0.58g,5mmol)、对溴苯丙酮(1.28g,6mmol)、醋酸铜(0.18g,1mmol)、bpy(0.16g,1mmol)和4-OH-TEMPO(0.86g,5mmol)的二甲基亚砜(10mL)溶液在120℃下搅拌反应24小时,反应结束后,用水和乙酸乙酯萃取,有机相用无水硫酸钠干燥,浓缩,用石油醚/乙酸乙酯=50/1(V/V)混合溶剂作洗脱剂,经硅胶柱层析分离得到白色固体6-(4-溴苯基)-2-甲基烟酸甲酯(Ⅰe)0.76g,收率:52%,熔点:106~107℃。
Ⅰe结构式为:
Figure GDA0001635428920000091
1HNMR(600MHz,CDCl3,ppm)δ8.30(d,J=7.8Hz,1H),7.98(d,J=8.4Hz,2H),7.64(d,J=7.8Hz,3H),3.96(s,3H),2.93(s,3H).13C NMR(150MHz,CDCl3,ppm)δ166.9,160.2,157.9,139.6,137.2,132.0,128.9,124.4,123.7,117.2,52.3,25.3.HRMS(ESI-TOF)calcdfor C14H13BrNO2[M+H]+:306.0117;Found:306.0124.
实施例6:6-(4-氟苯基)-2-苯基烟酸乙酯(Ⅰf)的制备
将3-氨基-3-苯基丙烯酸乙酯(9.56g,5mmol)、对氟苯丙酮(9.13g,6mmol)、醋酸铜(0.05g,0.25mmol)、TMEDA(0.06g,0.5mmol)和4-OH-TEMPO(0.86g,5mmol)的甲苯(10mL)溶液在120℃下搅拌反应24小时,反应结束后,用水和乙酸乙酯萃取,有机相用无水硫酸钠干燥,浓缩,用石油醚/乙酸乙酯=50/1(V/V)混合溶剂作洗脱剂,经硅胶柱层析分离得到油状液体6-(4-氟苯基)-2-苯基烟酸乙酯(Ⅰf)1.19g,收率:74%。
Ⅰf结构式为:
Figure GDA0001635428920000101
1H NMR(600MHz,CDCl3,ppm)δ8.21(d,J=7.8Hz,1H),8.16-8.14(m,2H),7.75(d,J=7.8Hz,1H),7.66-7.65(m,2H),7.50-7.46(m,3H),7.19(m,2H),4.20(q,J=7.2Hz,2H),1.10(t,J=7.2Hz,3H).13C NMR(150MHz,CDCl3,ppm))δ168.2,164.4(JC-F=248.3Hz),158.8,157.3,140.5,139.0,134.4(JC-F=3.1Hz),129,2(JC-F=8.6Hz),128.8,128.7,128.0,125.3,117.5,115.8(JC-F=21.5Hz),61.4,13.7.HRMS(ESI-TOF)calcd forC20H16FNNaO2[M+Na]+:344.1040;Found:305.1057.
实施例7:2-(对甲苯基)-5H-香豆素并[4,3-b]吡啶-5-酮(Ⅱa)的制备
将4-氨基香豆素(0.81g,5mmol)、对甲基苯丙酮(0.89g,6mmol)、醋酸铜(0.18g,1mmol)、TMEDA(0.23g,2mmol)和4-OH-TEMPO(0.86g,5mmol)的甲苯(10mL)溶液在120℃下搅拌反应24小时,反应结束后,用水和乙酸乙酯萃取,有机相用无水硫酸钠干燥,浓缩,用石油醚/乙酸乙酯=5/1(V/V)混合溶剂作洗脱剂,经硅胶柱层析分离得到白色固体2-(对甲苯基)-5H-香豆素并[4,3-b]吡啶-5-酮(Ⅱa)1.15g,收率:80%,熔点:201~202℃。
Ⅱa结构式为:
Figure GDA0001635428920000111
1H NMR(600MHz,CDCl3,ppm)δ8.77(d,J=7.8Hz,1H),8.63(d,J=8.4Hz,1H),8.17(d,J=7.8Hz,2H),7.94(d,J=8.4Hz,1H),7.62-7.59(m,1H),7.46-7.43(m,1H),7,42-7,03(s,1H)7,38(d,J=7.8Hz,2H),2.48(s,3H).13C NMR(150MHz,CDCl3,ppm)δ162.4,161.4,152.9,151.6,141.27,138.8,135.0,132.1,129.8,127.7,124.9,124.7,120.0,119.7,117.2,115.3,21.5.HRMS(ESI-TOF)calcd for C19H14NO2[M+H]+:288.1029;Found:288.1019.
实施例8:2-(4-甲氧基苯基)-9-叔丁基-5H-香豆素并[4,3-b]吡啶-5-酮(Ⅱb)的制备
于反应瓶中加入3-氨基-6-叔丁基-3-苯基丙烯酸乙酯(1.09g,5mmol)、对甲氧基苯丙酮(0.98g,6mmol)、醋酸铜(0.18g,1mmol)、bpy(0.16g,1mmol)和4-OH-TEMPO(0.86g,5mmol)的二氯苯(10mL)溶液在120℃下搅拌反应24小时,反应结束后,用水和乙酸乙酯萃取,有机相用无水硫酸钠干燥,浓缩,用石油醚/乙酸乙酯=5/1(V/V)混合溶剂作洗脱剂,经硅胶柱层析分离得到白色固体2-(4-甲氧基苯基)-9-叔丁基-5H-香豆素并[4,3-b]吡啶-5-酮(Ⅱb)1.37g,收率:76%,熔点:195~196℃。
Ⅱb结构式为:
Figure GDA0001635428920000121
1H NMR(600MHz,CDCl3,ppm)δ8.78-8.76(m,1H),8.62(d,J=8.4Hz,1H),8.28-8.25(m,2H),7.93(d,J=8.4Hz,1H),7.62-7.60(m,1H),7.46-7.43(m,1H),7.43(d,J=8.4Hz,1H)7.12-7.07(m,2H),3.94(s,3H).13C NMR(150MHz,CDCl3,ppm)δ162.1,162.0,161.4,152.9,151.7,138.7,132.0,130.3,129.3,124.9,124.7,119.7,119.5,117.2,114.9,114.4,55.5.HRMS(ESI-TOF)calcd for C19H14NO3[M+H]+:304.0962;Found:304.0968.
实施例9:2-(4-三氟甲基苯基)-9-叔丁基-5H-香豆素并[4,3-b]吡啶-5-酮(Ⅱc)的制备
于反应瓶中加入3-氨基-6-叔丁基-3-苯基丙烯酸乙酯(1.09g,5mmol)、对三氟甲基苯丙酮(1.21g,6mmol)、醋酸铜(0.18g,1mmol)、bpy(0.16g,1mmol)和4-OH-TEMPO(0.86g,5mmol)的二氯苯(10mL)溶液在120℃下搅拌反应24小时,反应结束后,用水和乙酸乙酯萃取,有机相用无水硫酸钠干燥,浓缩,用石油醚/乙酸乙酯=5/1(V/V)混合溶剂作洗脱剂,经硅胶柱层析分离得到白色固体2-(4-三氟甲基苯基)-9-叔丁基-5H-香豆素并[4,3-b]吡啶-5-酮(Ⅱc)1.77g,收率:89%,熔点:220~222℃。
Ⅱc结构式为:
Figure GDA0001635428920000131
1H NMR(600MHz,CDCl3,ppm)δ8.69(dd,J=7.8,1.8Hz,1H),8.66(d,J=8.4Hz,1H),8.34(d,J=7.2Hz,2H),7.95(d,J=7.8Hz,1H),7.82(d,J=7.8Hz,2H),7.62-7.59(m,1H),7.44-7.42(m,1H),7.38(d,J=7.8Hz,1H).13C NMR(150MHz,CDCl3,ppm)δ160.9,160.8,152.8,151.8,140.9,139.3,132.4,132.5(JC-F=32.0Hz)128.0,125.9(JC-F=3.8Hz),124.9(JC-F=8.0Hz),123.9(JC-F=170.6Hz)120.5,119.3,117.3,116.3.19F NMR(376MHz,CDCl3,ppm)δ=-62.7.HRMS(ESI-TOF)calcd for C19H11F3NO2[M+H]+:342.0723;Found:342.0736.
实施例10:2-(4-溴苯)-9-叔丁基-5H-香豆素并[4,3-b]吡啶-5-酮(Ⅱd)的制备
于反应瓶中加入3-氨基-6-叔丁基-3-苯基丙烯酸乙酯(1.09g,5mmol)、对溴苯丙酮(1.28g,6mmol)、氯化铁(0.08g,0.5mmol)、bpy(0.16g,1mmol)和4-OH-TEMPO(0.86g,5mmol)的二氯苯(10mL)溶液在120℃下搅拌反应24小时,反应结束后,用水和乙酸乙酯萃取,有机相用无水硫酸钠干燥,浓缩,用石油醚/乙酸乙酯=5/1(V/V)混合溶剂作洗脱剂,经硅胶柱层析分离得到白色固体2-(4-溴苯)-9-叔丁基-5H-香豆素并[4,3-b]吡啶-5-酮(Ⅱd)1.67g,收率:81%,熔点:206~207℃。
Ⅱd结构式:
Figure GDA0001635428920000141
1H NMR(600MHz,CDCl3,ppm)δ8.74(d,J=1.8Hz,1H),8.69(d,J=8.4Hz,1H),8.15(d,J=8.4Hz,2H),7.95(d,J=8.4Hz,1H),7.75(d,J=8.4Hz,2H),7.68-7.67(m,1H),7.38(d,J=9.0Hz,1H),1.47(s,9H).13C NMR(150MHz,CDCl3,ppm)δ161.4,161.3,152.1,150.9,148.0,139.3,136.8,132.3,129.9,129.26,125.6,120.9,119.9,118.6,116.9,115.9,34.8,31.5.HRMS(ESI-TOF)calcd for C22H18BrNO2[M+H]+:408.0544;Found:408.0594.
实施例11:抗肿瘤生物活性测试方法(MTT法)
将化合物Ⅰa、Ⅰb、Ⅰc、Ⅰd、Ⅰe、Ⅰf、Ⅱa、Ⅱb、Ⅱc、Ⅱd进行抗肿瘤活性测试,具体测试方法为将细胞用EDTA-胰酶消化液消化,并用DMEM培养基(每1000mL培养基中含80万单位青霉素,1.0g链霉素,10%灭火胎牛血清)稀释成1×106/mL培养基中,每孔100μL,置37℃,5%CO2培养箱中培养。接种24小时后,倾去培养基,加入培养基稀释的样品,每孔200μL,每个浓度加3孔,置37℃,5%CO2培养箱中培养,72小时后在细胞培养孔中加入5mg/mL的MTT,每孔10μL,置37℃孵育4小时,倾去培养基,加入DMSO,以相同条件用不含样品,含相同浓度DMSO的培养基培养的细胞作为对照,计算样品对肿瘤细胞生长的半数致死浓度(IC50),所得结果如下表1。
表1.吡啶衍生物对不同肿瘤细胞株的IC50(μM)值
Figure GDA0001635428920000151
Figure GDA0001635428920000161
Figure GDA0001635428920000171
从表1可以看出,本发明制备得到的此类化合物对人肺癌细胞A-549和人肝癌细胞HepG-2具有潜在的抗癌活性,从表1可以得出:
1)所有化合物对人肺癌细胞A-549具有一般的抑制活性;2)所有化合物中,化合物Ⅰb、Ⅱa、Ⅱb、Ⅱc对人肝癌细胞HepG-2具有较好的抑制活性,IC50值分别为36.92、16.92、4.112、3.47,其中化合物Ⅱc的抑制活性最好。
可见,本发明提供的吡啶衍生物(Ⅰ)和(Ⅱ)具有潜在的体外抗肿瘤细胞活性,具有开发成抗肿瘤药的前景。

Claims (1)

1.一种多取代吡啶衍生物在制备抑制人肝癌细胞HepG-2的抗肿瘤药物中的应用,所述的多取代吡啶衍生物的结构式如(Ⅰ)所示:
Figure DEST_PATH_IMAGE001
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