CN110156672A - 一种氨基脲化合物制备方法以及制得化合物的应用 - Google Patents

一种氨基脲化合物制备方法以及制得化合物的应用 Download PDF

Info

Publication number
CN110156672A
CN110156672A CN201910426622.3A CN201910426622A CN110156672A CN 110156672 A CN110156672 A CN 110156672A CN 201910426622 A CN201910426622 A CN 201910426622A CN 110156672 A CN110156672 A CN 110156672A
Authority
CN
China
Prior art keywords
base
methyl
pyridyl group
hydrazine
ethyl acetate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201910426622.3A
Other languages
English (en)
Other versions
CN110156672B (zh
Inventor
胡鸿雨
林郁梦
梅倩
郑希雅
张宇睿
郑绍成
严晓阳
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zhejiang Normal University CJNU
Original Assignee
Zhejiang Normal University CJNU
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zhejiang Normal University CJNU filed Critical Zhejiang Normal University CJNU
Priority to CN201910426622.3A priority Critical patent/CN110156672B/zh
Publication of CN110156672A publication Critical patent/CN110156672A/zh
Application granted granted Critical
Publication of CN110156672B publication Critical patent/CN110156672B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/803—Processes of preparation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/86—Hydrazides; Thio or imino analogues thereof
    • C07D213/87—Hydrazides; Thio or imino analogues thereof in position 3

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pyridine Compounds (AREA)

Abstract

本发明公开一种氨基脲化合物制备方法，包括以下步骤：步骤一、制备中间体2‑甲基‑6‑(吡啶基‑3‑基)乙酸乙酯；步骤二、制备中间体2‑甲基‑6‑(吡啶基‑3‑基)烟酸肼；步骤三、制备目标产物；将5.0mml 2‑甲基‑6‑(吡啶基‑3‑基)烟酸肼溶于10.0mL乙醇中，再加入5.5mmol取代异氰酸，回流3h；回流结束后趁热过滤并用乙醇洗涤3次，干燥得到目标产物；将制得的目标产物在制备治疗癌症疾病药物中进行应用；该发明反应成本低，产率高，反应过程简单易控制，适用于工业化生产。

Description

一种氨基脲化合物制备方法以及制得化合物的应用
技术领域
本发明涉及医药技术领域，特别是涉及一种氨基脲化合物制备方法以及制得化合物的应用。
背景技术
尽管继续进行研究，癌症仍然是人类健康面临的最大威胁之一，据估计，2010年全球死亡人数中，有15％是由癌症造成的。其中肝癌以本身的恶性度高、病情进展快，治疗难度大、疗效比较差，诊断后生存时间短而被称“癌中死亡率最高”。目前对肿瘤的治疗通常包括手术切除，其次是放疗和化疗，根据英国癌症研究中心的说法，最常见的化疗是丙卡嗪、卡莫司汀、洛莫司汀和长春新碱。然而，由于许多癌症的快速化学反应，这些药物本身就不足以长期治疗。其中多重耐药性是治疗癌症的主要障碍。传统的抗肿瘤药物绝大多数为细胞毒类药物，比如抗代谢药物和烷化剂等。而且这类药物的选择性很低，且毒性大。但随着分子生物学和细胞生物学的不断进步，科学家们把抗肿瘤药物的研发焦点转移到靶向药物上，这推动了各种高特异性、低毒性的新型抗癌药物发展。
开发高特异性、低毒性的新型抗癌药物，进而达到抗肿瘤的目的，具有很好的应用前景。因此设计合成具有生物利用度高、抗癌活性明显和毒性低等优点的新型抗癌药物是目前研究的热点。
发明内容
本发明的目的在于提供一种氨基脲化合物制备方法，该发明反应成本低，产率高，反应过程简单易控制，适用于工业化生产。
为解决此技术问题，本发明的技术方案是：一种氨基脲化合物制备方法，包括以下步骤：
步骤一、制备中间体2-甲基-6-(吡啶基-3-基)乙酸乙酯；
将5mmol的1-(3-吡啶基)-3-(二甲氨基)-2-丙烯-1-酮、5.5mmol乙酰乙酸乙酯和40mmol醋酸铵溶于15mL冰醋酸中，加料完成后回流5h；
然后冷至室温，接着把体系倾倒入100.0mL冰水中，得到黄色澄清溶液；
向体系加入30.0mL乙酸乙酯，进行萃取分液，重复3次，合并有机相后用无水Na2SO4干燥，过滤，滤液减压浓缩得到的粗产物用硅胶柱层析分离得到黄色固体产物2-甲基-6-(吡啶基-3-基)乙酸乙酯；
步骤二、制备中间体2-甲基-6-(吡啶基-3-基)烟酸肼；
将5.0mmol2-甲基-6-(吡啶基-3-基)乙酸乙酯溶于5.0mL乙醇中，再向其中加入2.0mL水合肼，加料结束后加热回流5h；
回流结束后冷至室温，过滤，乙醇洗涤，得到白色固体2-甲基-6-(吡啶基-3-基)烟酸肼；
步骤三、制备目标产物；
将5.0mml2-甲基-6-(吡啶基-3-基)烟酸肼溶于10.0mL乙醇中，再加入5.5mmol取代异氰酸，回流3h；
回流结束后趁热过滤并用乙醇洗涤3次，干燥得到目标产物。
优选步骤一中硅胶柱层析分离使用的洗脱剂为石油醚和乙酸乙酯的混合物，二者的体积比为3:1。本发明在制备步骤一中的中间体时使用硅胶柱层析利于获得纯度较高的2-甲基-6-(吡啶基-3-基)乙酸乙酯，利于后续中间体和目标产物的制备。
优选步骤一中2-甲基-6-(吡啶基-3-基)乙酸乙酯的收率为70％-85％；步骤一中1-(3-吡啶基)-3-(二甲氨基)-2-丙烯-1-酮，乙酰乙酸乙酯的摩尔配比为1：1.1。本发明中通过增大步骤一中乙酰乙酸乙酯的用量，促进反应正向进行，实现2-甲基-6-(吡啶基-3-基)乙酸乙酯的收率为70％-85％，利于提高本发明目标产物的产率和产量，降低生产成本。
优选步骤二中2-甲基-6-(吡啶基-3-基)烟酸肼的收率为80％-85％；步骤二中2-甲基-6-(吡啶基-3-基)乙酸乙酯和水合肼的摩尔配比为1：8.1。本发明中通过使用稍微过量的水合肼，促进反应正向进行，使得步骤二中2-甲基-6-(吡啶基-3-基)烟酸肼的收率为80％-85％，利于目标产物获得高收率。
优选步骤三中使用的取代异氰酸为2,4-二氟苯基异氰酸酯。本发明制得氨基脲对H460、Hela和MCF-7的体外抗肿瘤活性较高。
优选步骤三制得的目标产物的结构式如下：
其中R为2,4-二氟苯基。
优选步骤三制备目标产物的收率为80-90％；步骤三中2-甲基-6-(吡啶基-3-基)烟酸肼和取代异氰酸摩尔配比为1:1.1。本发明中通过使用稍微过量的取代异氰酸，促进反应正向进行，使得骤三制备目标产物的收率为80-90％，利于目标产物的制备。
本发明的另一个目的是提供一种具有新结构的氨基脲化合物在制备治疗癌症疾病药物方面的应用，该发明针对H460、Hela和MCF-7的体外抗肿瘤活性较高。
通过采用上述技术方案，本发明的有益效果是：
本发明通过两中间体的制备后制得一种氨基脲化合物，反应成本低，产率高，反应过程简单易控制，适用于工业化生产；
本发明制得氨基脲化合物具有一定的抗癌活性，对H460体外抗肿瘤活性达到11.5，对Hela体外抗肿瘤活性达到8.86，对MCF-7的体外抗肿瘤活性可达9.2，可用于制备抗肿瘤药物和研究该类化合物的构效关系。
从而实现本发明的上述目的。
具体实施方式
为了进一步解释本发明的技术方案，下面通过具体实施例来对本发明进行详细阐述。
实施例1
本发明公开一种氨基脲化合物制备方法，包括以下步骤：
步骤一、制备2-甲基-6-(吡啶基-3-基)乙基酸乙酯
将5mmol的1-(3-吡啶基)-3-(二甲氨基)-2-丙烯-1-酮(0.880g)、5.5mmol乙酰乙酸乙酯和40mmol醋酸铵溶于15mL冰醋酸中，加料完成后回流5h。然后冷至室温，接着把体系倾倒入100.0mL冰水中，得到黄色澄清溶液。向体系加入30.0mL乙酸乙酯，进行萃取分液，重复3次，合并有机相后用无水Na2SO4进行干燥，过滤除去干燥剂，旋蒸除去溶剂乙酸乙酯，得到黄色固体，柱层析提纯(洗脱剂：PE/EA＝4/1)，得到0.89g黄色晶体2-甲基-6-(吡啶基-3-基)乙基酸乙酯,产率73.5％，m.p.160-161℃,1H NMR(600MHz,DMSO-d6)9.32(d,J＝2.02Hz,1H),8.68(dd,J＝1.65,4.77Hz,1H),8.44-8.53(m,1H),8.28(d,J＝8.25Hz,1H),8.03(d,J＝8.25Hz,1H),7.55(dd,J＝4.77,8.07Hz,1H),4.34(q,J＝7.09Hz,2H),2.80(s,3H),1.35(t,J＝7.06Hz,3H)
步骤二、制备2-甲基-6-(吡啶基-3-基)烟酸肼
将5.0mmol2-甲基-6-(吡啶基-3-基)乙基酸乙酯(1.2g)溶于5.0mL乙醇中，再向其中加入2.0mL水合肼，加料结束后加热回流5h。回流结束后冷至室温，过滤出沉淀并用少量乙醇洗涤，得到0.93g白色固体2-甲基-6-(吡啶基-3-基)烟酸肼，产率81.5％,m.p.174.2-174.3℃,1H NMR(600MHz,DMSO-d6)9.65(s,8H),9.28(d,J＝1.83Hz,8H)，8.65(dd,J＝1.47,4.77Hz,8H),8.45(td,J＝1.79,7.98Hz,8H),7.94(d,J＝8.07Hz,8H),7.82(d,J＝7.89Hz,8H),7.53(dd,J＝4.77,7.89Hz,8H),4.56(br.s.,15H),2.62(s,24H)；13C NMR(150MHz,DMSO-d6)167.5,156.5,154.1,150.6,148.4,137.0,134.5,133.9,130.3,124.3,118.0,23.4。
步骤三、制备4-(2,4-二氟苯基)-1-(2-甲基-6-(吡啶-3-基)烟酰)氨基脲将5.0mml2-甲基-6-(吡啶基-3-基)烟酸肼(1.14g)溶于10.0mL乙醇中，再加入5.5mmol2,4-二氟苯基异氰酸酯，回流3h。TLC检测反应已结束，停止反应。反应液冷却至室温，抽滤，收集滤饼得到4-(2,4-二氟苯基)-1-(2-甲基-6-(吡啶-3-基)烟酰)氨基脲1.68g产率87.9％,m.p.291.9-293.6℃,1H NMR(600MHz,DMSO-d6):10.35(s,1H),9.32(d,J＝1.83Hz,1H),8.72(brs,1H),8.68(dd,J＝1.47,4.77Hz,1H),8.60(s,1H),8.49(td,J＝1.90,8.12Hz,1H),7.96-8.05(m,3H),7.55(ddd,J＝0.64,4.77,7.98Hz,1H),7.33(ddd,J＝2.93,8.80,11.37Hz,1H),7.02-7.11(m,1H),2.71(s,3H)；13C NMR(150MHz,DMSO-d6)168.2,158.5(d,J＝256.5Hz),156.8,155.7,154.6,150.7,148.4,137.3,134.6,133.8,129.4,124.3,118.0,111.6,111.4,104.5,104.3(d,J＝2.2Hz),104.2,23.4；HRMScalcd forC19H15F2N5O2[M+H]+384.1267,found 384.1275.
本实施例通过两中间体的制备后制得一种氨基脲化合物，反应成本低，产率高，反应过程简单易控制，适用于工业化生产。
采用溴化噻唑蓝四氮唑比色法(MTT)测试4-(2,4-二氟苯基)-1-(2-甲基-6-(吡啶-3-基)烟酰)氨基脲对人肺癌细胞(H460)、颈癌细胞(Hela)和人乳腺癌细胞(MCF-7)的体外抗肿瘤活性。取处于对数生长期的状态良好的细胞一瓶，加入0.25(wt)％胰蛋白酶消化液消化，使贴壁细胞脱落，计数，制成2～4×104个细胞/mL的悬液。接种于96孔板上，180μL/孔，置恒温CO2培养箱中培养24h。换液，加入受试化合物的DMSO溶液，20μL/孔，再加入含体积分数为10％的血清培养液80μL，培养48h。将MTT加入96孔板中，20μL/孔，培养箱中反应4h。吸去上清液，加入DMSO，150μL/孔，平板摇床上振摇5min。用酶联免疫检测仪在波长为570nm处测定每孔的光密度值(OD值)，并计算对细胞增殖的抑制率。以(Imatinib)为阳性对照。由以下公式:抑制率＝[(阴性对照组OD值-受试物组OD值)/阴性对照组OD值]×100％，计算不同浓度下的抑制率，再以此求出各样品的IC50值见如表1所示。
表1MTT测试4-(2,4-二氟苯基)-1-(2-甲基-6-(吡啶-3-基)烟酰)氨基脲对人肺癌细胞(H460)、颈癌细胞(Hela)和人乳腺癌细胞(MCF-7)的体外抗肿瘤活性情况列表
从表1中可知，本实施例制得的目标产物4-(2,4-二氟苯基)-1-(2-甲基-6-(吡啶-3-基)烟酰)氨基脲对人肺癌细胞(H460)、颈癌细胞(Hela)和人乳腺癌细胞(MCF-7)的体外抗肿瘤活性较高，具有一定的抗癌活性，可用于制备抗肿瘤药物和研究该类化合物的构效关系。

Claims (9)

1.一种氨基脲化合物制备方法，其特征在于：包括以下步骤：
步骤一、制备中间体2-甲基-6-(吡啶基-3-基)乙酸乙酯；
将5mmol的1-(3-吡啶基)-3-(二甲氨基)-2-丙烯-1-酮、5.5mmol乙酰乙酸乙酯和40mmol醋酸铵溶于15mL冰醋酸中，加料完成后回流5h；
然后冷至室温，接着把体系倾倒入100.0mL冰水中，得到黄色澄清溶液；
向体系加入30.0mL乙酸乙酯，进行萃取分液，重复3次，合并有机相后用无水Na2SO4干燥，过滤，滤液减压浓缩得到的粗产物用硅胶柱层析分离得到黄色固体产物2-甲基-6-(吡啶基-3-基)乙酸乙酯；
步骤二、制备中间体2-甲基-6-(吡啶基-3-基)烟酸肼；
将5.0mmol2-甲基-6-(吡啶基-3-基)乙酸乙酯溶于5.0mL乙醇中，再向其中加入2.0mL水合肼，加料结束后加热回流5h；
回流结束后冷至室温，过滤，乙醇洗涤，得到白色固体2-甲基-6-(吡啶基-3-基)烟酸肼；
步骤三、制备目标产物；
将5.0mml2-甲基-6-(吡啶基-3-基)烟酸肼溶于10.0mL乙醇中，再加入5.5mmol取代异氰酸，回流3h；
回流结束后趁热过滤并用乙醇洗涤3次，干燥得到目标产物。
2.如权利要求1所述的一种氨基脲化合物制备方法，其特征在于：步骤一中硅胶柱层析分离使用的洗脱剂为石油醚和乙酸乙酯的混合物，二者的体积比为3:1。
3.如权利要求1所述的一种氨基脲化合物制备方法，其特征在于：步骤一中2-甲基-6-(吡啶基-3-基)乙酸乙酯的收率为70％-85％。
4.如权利要求1所述的一种氨基脲化合物制备方法，其特征在于：步骤一中1-(3-吡啶基)-3-(二甲氨基)-2-丙烯-1-酮，乙酰乙酸乙酯的摩尔配比为1：1.1。
5.如权利要求1所述的一种氨基脲化合物制备方法，其特征在于：步骤二中2-甲基-6-(吡啶基-3-基)烟酸肼的收率为80％-85％；
步骤二中2-甲基-6-(吡啶基-3-基)乙酸乙酯和水合肼的摩尔配比为1：8.1。
6.如权利要求1所述的一种氨基脲化合物制备方法，其特征在于：步骤三中使用的取代异氰酸为2,4-二氟苯基异氰酸酯。
7.如权利要求6所述的一种氨基脲化合物制备方法，其特征在于：步骤三制得的目标产物的结构式如下：
其中R为2,4-二氟苯基。
8.如权利要求1所述的一种氨基脲化合物制备方法，其特征在于：步骤三制备目标产物的收率为80-90％；
步骤三中2-甲基-6-(吡啶基-3-基)烟酸肼和取代异氰酸摩尔配比为1:1.1。
9.一种将权利要求1至8任一项制得的氨基脲化合物在制备治疗癌症疾病药物方面的应用。
CN201910426622.3A 2019-05-22 2019-05-22 一种氨基脲化合物制备方法以及制得化合物的应用 Active CN110156672B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910426622.3A CN110156672B (zh) 2019-05-22 2019-05-22 一种氨基脲化合物制备方法以及制得化合物的应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910426622.3A CN110156672B (zh) 2019-05-22 2019-05-22 一种氨基脲化合物制备方法以及制得化合物的应用

Publications (2)

Publication Number Publication Date
CN110156672A true CN110156672A (zh) 2019-08-23
CN110156672B CN110156672B (zh) 2022-06-10

Family

ID=67631729

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910426622.3A Active CN110156672B (zh) 2019-05-22 2019-05-22 一种氨基脲化合物制备方法以及制得化合物的应用

Country Status (1)

Country Link
CN (1) CN110156672B (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115947716A (zh) * 2022-12-15 2023-04-11 厦门大学 一种靶向Nur77的吲哚衍生物及其应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107056713A (zh) * 2017-05-18 2017-08-18 厦门大学 4‑((4‑取代芳基‑2‑嘧啶基)氨基)苯甲酰肼衍生物及其制备方法和应用

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107056713A (zh) * 2017-05-18 2017-08-18 厦门大学 4‑((4‑取代芳基‑2‑嘧啶基)氨基)苯甲酰肼衍生物及其制备方法和应用

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
IAN R. BAXENDALE等: "The rapid preparation of 2-aminosulfonamide-1,3,4-oxadiazoles using polymer-supported reagents and microwave heating", 《TETRAHEDRON》 *
MOHAMED A. ABDELRAHMAN等: "Design, synthesis and 2D QSAR study of novel pyridine and quinolone hydrazone derivatives as potential antimicrobial and antitubercular agents", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 *
MOHAMED M. EL-KERDAWY等: "New benzimidazothiazole derivatives as anti-inflammatory, antitumor active agents: Synthesis, in-vitro and in-vivo screening and molecular modeling studies", 《BIOORGANIC CHEMISTRY》 *
WAGDY M. ELDEHNA等: "Design, Synthesis and Antitubercular Activity of Certain Nicotinic Acid Hydrazides", 《MOLECULES》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115947716A (zh) * 2022-12-15 2023-04-11 厦门大学 一种靶向Nur77的吲哚衍生物及其应用
CN115947716B (zh) * 2022-12-15 2024-02-27 厦门大学 一种靶向Nur77的吲哚衍生物及其应用

Also Published As

Publication number Publication date
CN110156672B (zh) 2022-06-10

Similar Documents

Publication Publication Date Title
CA2748289C (en) Preparation method of dihydroindene amide compounds,their pharmaceutical compositions containing compounds thereof and use as protein kinase inhibitor
EP1809622B1 (en) Inhibitors of the interaction between mdm2 and p53
CN105503827A (zh) Egfr抑制剂及其制备方法和用途
CN110546145B (zh) 一种氮杂芳基衍生物、其制备方法和在药学上的应用
CN105712932B (zh) 一种含1-甲基-3-芳基-4-氯吡唑结构的吡唑肟醚化合物的制备和应用
CN108610348A (zh) 一种含咪唑取代基的5H-色烯并[2,3-b]吡啶-3-腈衍生物及其制备与应用
CN108299398B (zh) 一种具有抗肿瘤活性含咔唑的喹唑啉衍生物及其制药用途
CN110156672A (zh) 一种氨基脲化合物制备方法以及制得化合物的应用
EP2832726B1 (en) (2-heteroarylamino)succinic acid derivative
CN102911118B (zh) 一类苯并氮杂卓类衍生物及其制备方法和用途
CN113563340B (zh) 一种苦参碱并嘧啶衍生物及其制备方法和应用
CN110078706B (zh) 一种伊马替尼衍生物及其制备方法和用途
CN109516959A (zh) 2-芳氨基-4-取代嘧啶类衍生物及其在制备抗肿瘤药物中的应用
CN115477639A (zh) 一种以fgfr1为靶点的多取代嘧啶类化合物及其制备方法和用途
CN108997319A (zh) 硫代咪唑烷酮衍生物及其合成方法与应用
CN108358841B (zh) 一类4-((2-取代喹啉-4-基)氨基)苯甲酰肼类衍生物及其制备方法与应用
CN109020883B (zh) 一种3-氰基-2-氨基吡啶类衍生物及其制备方法与应用
CN111518078B (zh) 一种含氨基吡啶的嘧啶类化合物及其应用
CN102146076B (zh) 苯胺喹唑啉衍生物及其制备方法
CN106632322B (zh) 一类吡唑中氮茚化合物及其制备方法与用途
CN111423413B (zh) 含(3-甲氧基-4-取代吡啶甲氧基)苯基单元的吡唑衍生物的制备与用途
CN111875605B (zh) 含取代吡唑和β-咔啉单元的双酰胺类化合物的制备与应用
CN113527215B (zh) 一种喹唑啉类化合物、制备方法及其应用
CN108101892A (zh) 一种白杨素非天然氨基酸衍生物及其制备方法和应用
JP7278649B2 (ja) Ｊａｋ阻害剤及びその製造方法

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant