[go: up one dir, main page]

CN104910236A - 吡唑基甾体衍生物及其制备方法、用途 - Google Patents

吡唑基甾体衍生物及其制备方法、用途 Download PDF

Info

Publication number
CN104910236A
CN104910236A CN201510363783.4A CN201510363783A CN104910236A CN 104910236 A CN104910236 A CN 104910236A CN 201510363783 A CN201510363783 A CN 201510363783A CN 104910236 A CN104910236 A CN 104910236A
Authority
CN
China
Prior art keywords
compound
substituent
steroid derivative
nmr
pyrazolyl
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
CN201510363783.4A
Other languages
English (en)
Other versions
CN104910236B (zh
Inventor
师宝君
李健
张继文
赵西梅
吴文君
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.)
Inst Of Pesticides Xibei Univ Of Agricultural & Forestry Science & Technolo
Original Assignee
Inst Of Pesticides Xibei Univ Of Agricultural & Forestry Science & Technolo
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 Inst Of Pesticides Xibei Univ Of Agricultural & Forestry Science & Technolo filed Critical Inst Of Pesticides Xibei Univ Of Agricultural & Forestry Science & Technolo
Priority to CN201510363783.4A priority Critical patent/CN104910236B/zh
Publication of CN104910236A publication Critical patent/CN104910236A/zh
Application granted granted Critical
Publication of CN104910236B publication Critical patent/CN104910236B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明公开了具有式(Ⅰ)结构的多种吡唑基甾体衍生物，其取代基R1代表氢、硝基或卤素；取代基R2代表C1-C6烷基、羟基取代的C1-C6烷基、单取代或多取代芳香基。其合成路线以孕烯醇酮为原料，本发明首次采用该方法合成此类衍生物，具有产率高、易分离等优点。这类衍生物显示抑制人肺腺癌细胞、子宫颈癌细胞系和人肝癌细胞的活性，具有被开发成抗癌药物或药物组合物的前景。

Description

吡唑基甾体衍生物及其制备方法、用途
技术领域
本发明属于药物合成技术领域，具体涉及多种吡唑基甾体衍生物，以及其优选的制备方法和在制备抗癌药物中的用途。
背景技术
甾体类化合物(steroids)是一类广泛存在于生物体内具有若干生理功能的有机化合物。甾体类化合物很早而且越来越多的被开发为药物，由于其特殊的结构以及活性特征使得越来越多的科研工作者不断的追求其结构的改造以求其活性的改变或者新的有益活性的出现。甾体分子中某些官能团的增加或者改变可以大幅度的提高化合物的药效、减少对人体的毒副作用，并能改变化合物作用性质，使其专属作用性变得单一。
一直以来癌症是人类健康的最大威胁，虽然现在的预防及治疗手段有所发展但是每年死于癌症的病人仍在增加。现有药物的治疗方法已经不能满足病症治疗的需要，迫切需要筛选出新型的抗癌药来应对多变的病症。基于甾体类药物的毒性低，利用率高，不易产生耐药性等优点，越来越多的甾体类药物被开发出来。
鉴于甾体类化合物所具有的特殊且广泛的生物活性，以及众多研究者进行结构修饰或改造从而赋予甾体类衍生物更多更新奇的活性，使其在农药、医药的应用和发掘中享有越来越重要的地位。为了寻找和开发更多更新型的甾体类药物在农药以及在医药领域的利用同时寻求活性较高的分子，本发明设计合成了一系列的甾体类衍生物，并评价其生物活性。
发明内容
本发明的目的在于提供多种化学结构新颖的吡唑基甾体衍生物，这些衍生物表现出良好的肿瘤细胞抑制活性，可以成为潜在的用于制备抗肿瘤药物的活性成分。本发明还探索了所述吡唑基甾体衍生物的高收率合成路线。
本发明的吡唑基甾体衍生物具有式(Ⅰ)的化学结构：
其中，取代基R1代表氢、硝基或卤素；取代基R2代表C1-C6烷基、羟基取代的C1-C6烷基、单取代或多取代芳香基。
进一步地，取代基R2优选为C1-C6直链烷基、羟基取代的C1-C6直链烷基、单取代或多取代苯基。
作为取代基R2的进一步优选，取代基R2可以为C1-C3直链烷基、羟基取代的C1-C3直链烷基、单取代或具有两个取代基的苯基。
对于取代基R1，R1选自氢、硝基、或卤素，所述卤素代表氟、氯、溴、碘，但优选为氯。取代基R2进一步代表乙基、2-羟乙基、邻甲基苯基、间甲基苯基、邻甲氧基苯基、2-氟对甲基苯基、3-氯-2-甲基苯基或3,5-三氟甲基苯基。
为了详实的描述式(Ⅰ)吡唑基甾体衍生物的结构，本发明定义上下文中的术语。
术语“烷基”应指从烷烃的任一碳原子上除去氢原子而衍生的一价基团，“烷基”的碳原子形成直链或支链的骨架，因此，“烷基”可分为“直链烷基”和“支链烷基”。该术语包括伯、仲、叔烷基子类，如甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、正己基、异己基。特别地，术语“烷烃”是指仅仅含有碳、氢的饱和烃化合物。
术语“羟基取代的C1-C6烷基”应理解为烷基上的一个或多个氢原子被羟基替代的基团。而“羟基”应表示-OH的基团。例如，乙基的2号位碳上的氢被羟基取代，形成2-羟乙基。
术语“芳香基”又可以称为“芳基”，应包括碳环芳环基团，碳原子数为C6-C10芳环基团，比如苯基(C6)、萘基(C10)和C8芳环基团。
术语“单取代芳香基”应理解为芳香基其中一个碳原子的氢被其它的基团取代。例如，芳香基若为苯基，这个氢可以被卤素(氟、氯、溴或碘)取代，形成邻、间、对卤代苯基；或被甲基取代，形成邻甲基苯基、间甲基苯基、对甲基苯基；或被甲氧基取代，形成邻甲氧基苯基、间甲氧基苯基、对甲氧基苯基。芳香基若为萘基，与此类似，在此不作详述。
术语“多取代芳香基”应指芳香基其中两个或两个以上碳原子的氢被其它的基团取代。例如，芳香基若为苯基，两个氯原子，或两个氟原子，或一个氯原子一个氟原子可以取代不同碳原子上的氢；苯环上的氢被甲基和氟取代，可以形成2-氟对甲基苯基；或苯环上的氢被甲基和氯取代，可以形成3-氯-2-甲基苯基；或苯环上的氢被两个三氟甲基取代，可以形成3,5-三氟甲基苯基。芳香基若为萘基，与此类似，在此不作详述。
术语“卤素”应代表氟、氯、溴或碘。
术语“硝基”应表示-NO2的基团。
进一步地，本发明还给出了一些具体机构的吡唑基甾体衍生物，例如化合物5.1-5.27，均具有式(Ⅰ)的取代基R1和R2。取代基R1可以代表氢、硝基或氯；取代基R2可以代表乙基、2-羟乙基、邻甲基苯基、间甲基苯基、邻甲氧基苯基、2-氟对甲基苯基、3-氯-2-甲基苯基或3,5-三氟甲基苯基；取代基R1和R2组合，形成结构差异的不同化合物。具体而言：
吡唑基甾体衍生物(化合物5.1)，取代基R1是氢并且R2是乙基。
吡唑基甾体衍生物(化合物5.2)，取代基R1是氢并且R2是2-羟乙基。
吡唑基甾体衍生物(化合物5.3)，取代基R1是氢并且R2是苯基。
吡唑基甾体衍生物(化合物5.4)，取代基R1是氢并且R2是间甲基苯基。
吡唑基甾体衍生物(化合物5.5)，取代基R1是氢并且R2是邻甲基苯基。
吡唑基甾体衍生物(化合物5.6)，取代基R1是氢并且R2是邻甲氧基苯基。
吡唑基甾体衍生物(化合物5.7)，取代基R1是氢并且R2是2-氟对甲基苯基。
吡唑基甾体衍生物(化合物5.8)，取代基R1是氢并且R2是3-氯-2-甲基苯基。
吡唑基甾体衍生物(化合物5.9)，取代基R1是氢并且R2是3,5-三氟甲基苯基。
还有，吡唑基甾体衍生物(化合物5.10)，取代基R1是硝基并且R2是乙基。
吡唑基甾体衍生物(化合物5.11)，取代基R1是硝基并且R2是2-羟乙基。
吡唑基甾体衍生物(化合物5.12)，取代基R1是硝基并且R2是苯基。
吡唑基甾体衍生物(化合物5.13)，取代基R1是硝基并且R2是间甲基苯基。
吡唑基甾体衍生物(化合物5.14)，取代基R1是硝基并且R2是邻甲基苯基。
吡唑基甾体衍生物(化合物5.15)，取代基R1是硝基并且R2是邻甲氧基苯基。
吡唑基甾体衍生物(化合物5.16)，取代基R1是硝基并且R2是2-氟对甲基苯基。
吡唑基甾体衍生物(化合物5.17)，取代基R1是硝基并且R2是3-氯-2-甲基苯基。
吡唑基甾体衍生物(化合物5.18)，取代基R1是硝基并且R2是3,5-三氟甲基苯基。
还有，吡唑基甾体衍生物(化合物5.19)，取代基R1是氯并且R2是乙基。
吡唑基甾体衍生物(化合物5.20)，取代基R1是氯并且R2是2-羟乙基。
吡唑基甾体衍生物(化合物5.21)，取代基R1是氯并且R2是苯基。
吡唑基甾体衍生物(化合物5.22)，取代基R1是氯并且R2是间甲基苯基。
吡唑基甾体衍生物(化合物5.23)，取代基R1是氯并且R2是邻甲基苯基。
吡唑基甾体衍生物(化合物5.24)，取代基R1是氯并且R2是邻甲氧基苯基。
吡唑基甾体衍生物(化合物5.25)，取代基R1是氯并且R2是2-氟对甲基苯基。
吡唑基甾体衍生物(化合物5.26)，取代基R1是氯并且R2是3-氯-2-甲基苯基。
吡唑基甾体衍生物(化合物5.27)，取代基R1是氯并且R2是3,5-三氟甲基苯基。
进一步地，其中三种吡唑基甾体衍生物，例如化合物6.1-6.3，具有式(Ⅰ)的取代基R1，而无取代基R2。取代基R1选自氢、硝基或氯，分别形成化合物6.1-6.3。
为了合成具有式(Ⅰ)结构的吡唑基甾体衍生物，本发明给出了优选的设计合成路线。合成路线包括下述步骤：
(a)选用孕烯醇酮(化合物1)作为各个吡唑基甾体衍生物的合成中间体，分别与苯肼盐酸盐、对硝基苯肼盐酸盐、对氯苯肼盐酸盐在乙酸钠的催化下生成中间产物苯腙(化合物2.1-2.3)；
(b)化合物2.1-2.3在三氯氧磷的催化下发生关环反应，获得具有吡唑环的化合物3.1-3.3；
(c)将化合物3.1-3.3水解得到去甲酰基的化合物4.1-4.3；
(d)或以硼氢化钠为还原剂，将化合物4.1-4.3还原获得化合物6.1-6.3；或化合物4.1-4.3在三乙酰氧基硼氢化钠的催化下与乙胺发生胺化还原反应得到化合物5.1-5.27。
上述的吡唑基甾体衍生物(化合物5.1-5.27和化合物6.1-6.3)均为全新的化合物。本发明推荐的合成路线也是在合成此类化合物中首次成功应用，该合成路线新颖、产率高并且产物易于分离，可以说是制备此类化合物的最优路线。式(Ⅰ)结构的吡唑基甾体衍生物的具体合成方法，在实施例中有详细的记载。
这些衍生物对活体或离体组织、生物体的作用机理目前还不清楚，但发明人惊奇的发现，具有式(Ⅰ)结构的吡唑基甾体衍生物对人肺腺癌细胞(A549)、子宫颈癌细胞系(Hela)和人肝癌细胞(HepG2)的增殖均具有良好的抑制活性，其IC50介于0.91uM-3.89uM之间。发明人根据上述发现初步推测，吡唑基甾体衍生物可以与药学上可接受的赋形剂或载体相配伍，用于制备抗癌药物或药物组合物。作为优选，上述抗癌药物或药物组合物用于抑制人肺腺癌细胞、子宫颈癌细胞系或人肝癌细胞的活性。同时，上述发现还激发了发明人进一步研究合成的吡唑基甾体衍生物的作用机理或作用靶标部位，以及尝试制备抗癌药物或药物组合物。
为了便于药物吸收或将药物输送至靶位，包含至少一种式(Ⅰ)结构的吡唑基甾体化合物(或称为活性成分)的抗癌药物或药物组合物，还应有药学上可接受的赋形剂或载体，并制成适宜的供药剂型，比如颗粒剂、片剂、丸剂、糖衣丸、栓剂、胶囊剂、胶囊缓释剂、缓释片剂、混悬剂或注射液等制剂形式。药学上可接受的赋形剂或载体，或称为药物制剂上用的辅料，如水、硬脂酸镁、滑石、淀粉、有机酸、葡聚糖或类脂质等，适于口、肠、胃肠外或局部施用的药物辅料。
在以下实施例中进一步描述本发明，而不以任何形式旨在限制如权利要求所表明的本发明的保护范围。
具体实施方式
实施例一
化学合成制备式(I)的吡唑基甾体衍生物，可参照下述步骤进行。
(1)将6.32g(20mmol)孕烯醇酮1溶解于有150mL冰醋酸的250mL茄型烧瓶中，搅拌待完全溶解；然后分批加入苯肼盐酸盐衍生物(22mmol)，搅拌超声至溶解；量取3.46mL(25mmol)三乙胺，常温下慢慢滴入反应体系中，半小时后滴毕，常温搅拌6h待有固体析出，抽滤，并用冰醋酸洗涤，烘干得目标化合物2.1-2.3约7.8g，本步骤的产物无需分离可直接用于下一步反应。
(2)首先制备visemier试剂：取充分干燥的圆底烧瓶，向内加入20mL干燥过的DMF溶液，搅拌下向内慢慢滴加三氯氧磷溶液(4.65mL，50mmol)，半小时后滴毕，整个制备visemier试剂期间温度需保持在0℃，混合液继续搅拌反应20min待用。
将底物甾体苯腙(10mmol)溶解于30mL无水DMF中，0℃下，将此慢慢滴入所准备的visemier试剂中，此过程需30min，滴毕后继续搅拌24h，检测反应至完全。此时将反应体系倒入饱和的碳酸氢钠溶液中，搅拌至有固体析出，抽滤得到目标产物的粗品然后溶解于二氯甲烷中萃取三次，所得有机相合并干燥，过滤、柱分(石油醚：乙酸乙酯＝4:1)得到目标化合物3.1-3.3纯品约3g。
(3)取吡唑基孕烯醇5mmol，溶于20mL四氢呋喃和20mL甲醇的混合溶液中，然后加入碳酸钾(5.5mmol，759mg)，超声搅拌至完全溶解。加热回流2h，检测反应至完全，进而用旋转蒸发仪除去溶剂，利用乙酸乙酯萃取三次，合并有机相，柱分得到目标化合物4.1-4.2约4.8mmol。
(4)取去甲酰化的吡唑基孕烯醇0.5mmol溶于10mL四氢呋喃和10mL甲醇的混合溶液中，然后分批加入硼氢化钠(38mg，1mmol)，室温反应1h后，检测反应完毕用冰醋酸淬灭，然后用乙酸乙酯萃取三次，合并有机相，柱分(石油醚：乙酸乙酯＝1:1)得目标产物6.1-6.3约0.48mmol。
(5)取25mL的干燥圆底烧瓶，将1mmol去甲酰化的吡唑基孕烯醇溶于除水的1,2-二氯乙烷15mL中，搅拌下加入苯胺衍生物1.1mmol，而后分批加入三乙酰基硼氢化钠，常温搅拌8h，检测反应，待反应完全后加入饱和的碳酸氢钠溶液淬灭，然后用二氯甲烷萃取三次，合并有机相，柱分(二氯甲烷：甲醇＝10:1)得到胺化还原产物5.1-5.27约0.75mmol。
实施例二
对实施例一合成的目标化合物以及重要的中间体进行结构鉴定，各化合物的结构通过1H-NMR、13C-NMR、DEPT1350确认。
化合物3.1
化合物3.1为关键的中间体，其结构通过单晶衍射的方法予以确认，结果如下。
1H-NMR(CDCl3,500MHz):δ(ppm)9.96(s,1H),8.39(s,1H),8.04(s,1H),7.72(d,2H,J＝7.5Hz),7.48(t,2H,J＝7.5Hz),7.34(t,1H,J＝7.5Hz),5.43-5.42(m,1H),4.75(m,1H),3.28(t,1H,J＝10.0Hz),2.60-2.53(m,1H),2.38-2.37(m,2H),2.10-2.01(m,2H),1.92-1.79(m,3H),1.68-1.52(m,6H),1.45-1.14(m,5H),1.03(s,3H),0.64(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)184.90(CH),160.64(CH),155.53(C),139.42(C),139.33(C),130.65(CH),129.59(CH),129.59(CH),127.49(CH),123.93(C),122.82(CH),119.58(CH),119.58(CH),73.92(CH),56.52(CH),50.14(CH),48.38(CH),44.65(C),38.07(CH2),37.99(CH2),36.95(CH2),36.69(C),32.38(CH),31.90(CH2),27.76(CH2),25.96(CH2),24.62(CH2),20.89(CH2),19.34(CH3),13.46(CH3)。
化合物3.2
1H-NMR(CDCl3,500MHz):δ(ppm)10.01(s,1H),8.52(s,1H),8.38(d,2H,J＝9.0Hz),8.05(s,1H),7.94(d,2H,J＝9.0Hz),5.44(m,1H),4.79-4.73(m,1H),3.31(t,1H,J＝10.0Hz),2.60-2.52(m,1H),2.40-2.04(m,4H),1.93-1.83(m,3H),1.69-1.54(m,5H),1.47-1.08(m,6H),1.04(s,3H),0.66(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)184.61(CH),160.62(CH),156.74(C),146.20(C),143.51(C),139.43(C),131.06(CH),125.43(CH),125.43(CH),125.05(C),122.75(CH),119.25(CH),119.25(CH),73.85(CH),56.55(CH),50.09(CH),48.39(CH),44.80(C),38.06(CH2),38.01(CH2),36.96(CH2),36.68(C),32.37(CH),31.87(CH2),27.75(CH2),26.02(CH2),24.60(CH2),20.88(CH2),19.34(CH3),13.51(CH3)。
化合物3.3
1H-NMR(CDCl3,500MHz):δ(ppm)9.95(s,1H),8.36(s,1H),8.04(s,1H),7.67(d,2H,J＝9.0Hz),7.45(d,2H,J＝9.0Hz),5.42(m,1H),4.75(m,1H),3.27(t,1H,J＝10.0Hz),2.54(m,1H),2.38-2.00(m,4H),1.92-1.79(m,3H),1.67-1.51(m,6H),1.44-1.21(m,5H),1.02(s,3H),0.63(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)184.75(CH),160.62(CH),155.77(C),139.42(C),137.85(C),133.10(C),130.51(CH),129.70(CH),129.70(CH),124.17(C),122.79(CH),120.67(CH),120.67(CH),73.89(CH),56.52(CH),50.12(CH),48.35(CH),44.66(C),38.07(CH2),37.99(CH2),36.95(CH2),36.69(C),32.37(CH),31.89(CH2),27.76(CH2),25.98(CH2),24.60(CH2),20.88(CH2),19.34(CH3),13.46(CH3)。
化合物4.1
1H-NMR(CDCl3,500MHz):δ(ppm)9.96(s,1H),8.39(s,1H),7.73(d,2H,J＝7.5Hz),7.48(t,2H,J＝7.5Hz),7.35(t,1H,J＝7.5Hz),5.38-5.37(m,1H),3.57-3.51(m,1H),3.27(t,1H,J＝10.0Hz),2.60-2.52(m,1H),2.34-2.04(m,2H),2.10-2.01(m,2H),1.87-1.66(m,4H),1.64-1.39(m,8H),1.35-1.03(m,3H),1.01(s,3H),0.64(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)184.92(CH),155.57(C),140.89(C),139.34(C),130.65(CH),129.59(CH),129.59(CH),127.49(CH),123.92(C),121.52(CH),119.58(CH),119.58(CH),71.75(CH),56.61(CH),50.26(CH),48.40(CH),44.67(C),42.29(CH2),38.06(CH2),37.29(CH2),36.63(C),32.45(CH),31.93(CH2),31.66(CH2),25.97(CH2),24.64(CH2),20.94(CH2),19.44(CH3),13.46(CH3)。
化合物4.2
1H-NMR(CDCl3,500MHz):δ(ppm)10.01(s,1H),8.47(s,1H),8.37(d,2H,J＝9.0Hz),7.91(d,2H,J＝9.0Hz),5.36-5.35(m,1H),3.48-3.42(m,1H),3.32(t,1H,J＝10.0Hz),2.35-2.21(m,4H),2.14-2.07(m,1H),1.99-1.93(m,1H),1.86-1.60(m,6H),1.56-1.38(m,6H),1.05(s,3H),0.99(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)184.44(CH),159.84(C),146.07(C),143.46(C),140.71(C),131.48(CH),125.44(CH),125.44(CH),124.96(C),121.58(CH),119.11(CH),119.11(CH),71.74(CH),50.65(CH),49.69(CH),46.68(CH),45.33(C),42.22(CH2),37.17(CH2),36.48(CH2),34.65(C),32.28(CH),32.15(CH2),31.56(CH2),27.12(CH2),26.04(CH2),20.84(CH2),20.22(CH3),19.38(CH3)。
化合物4.3
1H-NMR(CDCl3,500MHz):δ(ppm)9.92(s,1H),8.50(s,1H),7.72(d,2H,J＝9.0Hz),7.46(d,2H,J＝9.0Hz),5.38-5.37(m,1H),3.52-3.46(m,1H),3.29(t,1H,J＝10.0Hz),2.54(m,1H),2.31-2.20(m,2H),2.09-2.01(m,2H),1.91-1.78(m,3H),1.75-1.51(m,4H),1.49-1.30(m,6H),1.07-1.05(m,2H)1.01(s,3H),0.64(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)185.84(CH),156.25(C),141.23(C),138.04(C),133.42(C),130.58(CH),129.89(CH),129.89(CH),124.21(C),121.58(CH),121.09(CH),121.09(CH),71.74(CH),56.85(CH),50.53(CH),48.59(CH),44.96(C),42.07(CH2),38.25(CH2),37.54(CH2),36.86(C),32.68(CH),32.12(CH2),31.37(CH2),26.18(CH2),24.82(CH2),21.15(CH2),19.54(CH3),13.60(CH3)。
化合物5.1
1H-NMR(CDCl3&CD3OD,500MHz):δ(ppm)8.02(s,1H),7.67(d,2H,J＝9.0Hz),7.42(t,2H,J＝9.0Hz),7.23(t,1H,J＝8.0Hz),5.37(m,1H),3.80-3.73(m,2H),3.60(s,1H),3.53-3,47(m,1H),2.80-2.72(m,3H)2.50-2.43(m,1H),2.31-1.95(m,4H),1.86-1.76(m,3H),1.63-1.35(m,8H),1.31-1.24(m,2H),1.20(t,3H,J＝7.0Hz),1.31-1.06(m,1H),1.01(s,3H),0.68(s,3H)。
13C-NMR(CDCl3&CD3OD,125MHz):δ(ppm)152.20(C),141.00(C),140.32(C),129.40(CH),129.40(CH),126.86(CH),126.04(CH),121.57(CH),118.98(CH),118.98(CH),118.71(C),71.46(CH),56.70(CH),50.43(CH),48.55(CH),44.63(C),43.21(CH2),42.59(CH2),42.07(CH2),38.53(CH2),37.41(CH2),36.72(C),32.47(CH),32.00(CH2),31.37(CH2),26.84(CH2),24.68(CH2),21.07(CH2),19.47(CH3),14.01(CH3),13.35(CH3)。
化合物5.2
1H-NMR(CDCl3&CD3OD,500MHz):δ(ppm)8.05(s,1H),7.67(d,2H,J＝7.5Hz),7.43(t,2H,J＝7.5Hz),7.26(t,1H,J＝8.0Hz),5.37(m,1H),3.86-3.79(m,2H),3.75-3.73(m,2H),3.51-3,45(m,1H),2.88-2.86(m,2H)2.77(t,1H,J＝10Hz),2.50-2.42(m,1H),2.30-1.96(m,4H),1.86-1.77(m,3H),1.63-1.26(m,11H),1.12-0.96(m,6H),1.01(s,3H),0.68(s,3H)。
13C-NMR(CDCl3&CD3OD,125MHz):δ(ppm)152.49(C),141.13(C),140.37(C),129.52(CH),129.52(CH),127.22(CH),126.32(CH),121.62(CH),119.24(CH),119.24(CH),118.50(C),71.42(CH),59.85(CH),56.76(CH2),50.54(CH),50.47(CH2),48.61(CH),44.79(C),42.88(CH2),42.03(CH2),38.60(CH2),37.52(CH2),36.81(C),32.58(CH),32.08(CH2),31.33(CH2),26.81(CH2),24.76(CH2),21.15(CH2),19.51(CH3),13.40(CH3)。
化合物5.3
1H-NMR(CDCl3,500MHz):δ(ppm)7.83(s,1H),7.64(d,2H,J＝7.5Hz),7.40(t,2H,J＝7.5Hz),7.23-7.18(m,3H),6.75(t,1H,J＝7.0Hz),6.74(t,1H,J＝7.5Hz),6.66(d,2H,J＝7.5Hz),5.37-5.36(m,1H),4.22-4.16(m,2H),3.75(s,1H),3.56-3.49(m,1H),2.81(t,1H,J＝10.0Hz),2.51-2.43(m,1H),2.32-2.21(m,2H),2.07-1.97(m,2H),1.86-1.70(m,4H),1.63-1.46(m,6H),1.40-1.05(m,4H),1.01(s,3H),0.73(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.15(C),148.16(C),140.81(C),140.35(C),129.32(CH),129.32(CH),129.30(CH),129.30(CH),125.97(CH),125.73(CH),121.63(CH),120.31(C),118.65(CH),118.65(CH),117.71(CH),112.92(CH),112.92(CH),71.76(CH),56.54(CH),50.28(CH),48.54(CH),44.55(C),42.32(CH2),38.78(CH2),38.45(CH2),37.31(CH2),36.63(C),32.40(CH),31.92(CH2),31.67(CH2),26.91(CH2),24.65(CH2),21.03(CH2),19.45(CH3),13.44(CH3)。
化合物5.4
1H-NMR(CDCl3,500MHz):δ(ppm)7.83(s,1H),7.65(d,2H,J＝7.5Hz),7.40(t,2H,J＝8.0Hz),7.16(t,1H,J＝8.0Hz),7.21(t,1H,J＝7.5Hz),7.09(t,1H,J＝8.0Hz),6.57(d,1H,J＝7.5Hz),6.51-6.47(m,2H),5.37-5.36(m,1H),4.21-4.14(m,2H),3.68(s,1H),3.56-3.49(m,1H),2.81(t,1H,J＝10.0Hz),2.50-2.42(m,1H),2.32-2.21(m,2H),2.30(s,3H),2.07-1.96(m,2H),1.86-1.70(m,4H),1.62-1.45(m,6H),1.43-1.05(m,4H),1.01(s,3H),0.73(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.15(C),148.20(C),140.80(C),140.34(C),139.10(C),129.29(CH),129.29(CH),129.19(CH),127.23(CH),125.97(CH),125.71(CH),121.63(CH),120.41(C),118.66(CH),118.66(CH),113.72(CH),110.04(CH),71.75(CH),56.52(CH),50.26(CH),48.51(CH),44.53(C),42.30(CH2),38.78(CH2),38.40(CH2),37.30(CH2),36.62(C),32.38(CH),31.92(CH2),31.65(CH2),26.92(CH2),24.64(CH2),21.66(CH2),21.01(CH3),19.45(CH3),13.44(CH3)。
化合物5.5
1H-NMR(CDCl3,500MHz):δ(ppm)7.85(s,1H),7.66(d,2H,J＝7.5Hz),7.41(t,2H,J＝8.0Hz),7.22(t,1H,J＝7.5Hz),7.16(t,1H,J＝8.0Hz),7.08(d,1H,J＝7.5Hz),6.72-6.69(m,2H),5.37-5.36(m,1H),4.25-4.18(m,2H),3.56(s,1H),3.54-3.50(m,1H),2.83(t,1H,J＝10.0Hz),2.51-2.43(m,1H),2.32-2.22(m,2H),2.13(s,3H),2.08-1.97(m,2H),1.86-1.70(m,4H),1.62-1.47(m,6H),1.46-1.05(m,4H),1.01(s,3H),0.75(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.31(C),146.11(C),140.79(C),140.32(C),130.10(C),129.31(CH),129.31(CH),127.22(CH),126.09(CH),125.76(CH),122.01(CH),121.62(CH),120.32(C),118.67(CH),118.67(CH),117.26(CH),109.86(CH),71.74(CH),56.50(CH),50.24(CH),48.50(CH),44.50(C),42.29(CH2),38.68(CH2),38.40(CH2),37.29(CH2),36.62(C),32.38(CH),31.90(CH2),31.64(CH2),27.01(CH2),24.65(CH2),20.97(CH2),19.45(CH3),17.56(CH3),13.44(CH3)。
化合物5.6
1H-NMR(CDCl3,500MHz):δ(ppm)7.85(s,1H),7.65(d,2H,J＝7.5Hz),7.40(t,2H,J＝8.0Hz),7.22(t,1H,J＝7.5Hz),6.90(t,1H,J＝8.0Hz),6.79(d,1H,J＝7.5Hz),6.72-6.68(m,2H),5.37-5.36(m,1H),4.32(s,1H),4.23-4.18(m,2H),3.83(s,3H),3.56-3.50(m,1H),2.82(t,1H,J＝10.0Hz),2.51-2.43(m,1H),2.32-2.21(m,2H),2.07-1.97(m,2H),1.86-1.71(m,4H),1.62-1.48(m,6H),1.46-1.05(m,4H),1.01(s,3H),0.74(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.15(C),146.87(C),140.80(C),140.39(C),138.19(C),129.27(CH),129.27(CH),126.04(CH),125.65(CH),121.64(CH),121.32(CH),120.44(CH),118.63(CH),118.63(CH),116.78(C)，110.11(CH),109.42(CH),71.75(CH),56.53(CH),55.40(CH3),50.28(CH),48.53(CH),44.52(C),42.31(CH2),38.57(CH2),38.38(CH2),37.30(CH2),36.62(C),32.39(CH),31.92(CH2),31.65(CH2),26.89(CH2),24.65(CH2),21.02(CH2),19.45(CH3),13.44(CH3)。
化合物5.7
1H-NMR(CDCl3,500MHz):δ(ppm)7.83(s,1H),7.65(d,2H,J＝7.5Hz),7.40(t,2H,J＝7.5Hz),7.21(t,1H,J＝7.5Hz),6.83-6.81(m,2H),6.66(t,1H,J＝8.5Hz),5.38-5.37(m,1H),4.23-4.16(m,2H),3.87(s,1H),3.56-3.50(m,1H),2.80(t,1H,J＝10.0Hz),2.51-2.43(m,1H),2.32-2.28(m,1H),2.25(s,3H),2.07-1.97(m,2H),1.86-1.70(m,4H),1.63-1.48(m,6H),1.43-1.05(m,5H),1.01(s,3H),0.73(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.07(C),151.49(C,J＝237.50Hz),140.80(C),140.32(C),134.10(C,J＝11.875Hz),129.28(CH),129.28(CH),126.53(C,J＝6.50Hz),125.94(CH),125.73(CH),124.75(CH,J＝2.875Hz),121.61(CH),120.08(C),118.66(CH),118.66(CH),115.26(CH,J＝18.0Hz),112.45(CH,d,J＝3.50Hz),71.75(CH),56.54CH),50.27(CH),48.58(CH),44.52(C),42.30(CH2),38.80(CH2),38.41(CH2),37.30(CH2),36.62(C),32.38(CH),31.91(CH2),31.64(CH2),26.88(CH2),24.63(CH2),21.00(CH2),20.37(CH3),19.44(CH3),13.42(CH3)。
化合物5.8
1H-NMR(CDCl3,500MHz):δ(ppm)7.83(s,1H),7.66(d,2H,J＝7.5Hz),7.42(t,2H,J＝7.5Hz),7.23(t,1H,J＝7.5Hz),7.05(t,1H,J＝7.5Hz),6.80(d,1H,J＝7.5Hz),6.58(d,1H,J＝7.5Hz),5.37-5.36(m,1H),4.24-4.17(m,2H),3.67(s,1H),3.55-3.50(m,1H),2.80(t,1H,J＝10.0Hz),2.50-2.44(m,1H),2.32-2.21(m,2H),2.19(s,3H),2.07-1.97(m,2H),1.86-1.69(m,4H),1.62-1.45(m,8H),1.43-1.05(m,2H),1.01(s,3H),0.75(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.28(C),147.22(C),140.79(C),140.27(C),134.62(C),129.34(CH),129.34(CH),127.31(CH),126.06(CH),125.86(CH),121.61(CH),119.83(C),119.63(C),118.68(CH),118.68(CH),118.23(CH),108.28(CH),71.75(CH),56.52(CH),50.24(CH),48.54(CH),44.52(C),42.30(CH2),38.90(CH2),38.45(CH2),37.30(CH2),36.62(C),32.38(CH),31.90(CH2),31.65(CH2),27.02(CH2),24.64(CH2),20.97(CH2),19.45(CH3),13.58(CH3),13.44(CH3)。
化合物5.9
1H-NMR(CDCl3,500MHz):δ(ppm)7.84(s,1H),7.65(d,2H,J＝7.5Hz),7.43(t,2H,J＝8.0Hz),7.19(s,1H),6.90(t,1H),6.79(s,2H),5.39-5.38(m,1H),4.28-4.21(m,3H),3.57-3.51(m,1H),2.79(t,1H,J＝10.0Hz),2.52-2.44(m,1H),2.34-2.22(m,2H),2.09-1.98(m,2H),1.89-1.70(m,4H),1.64-1.47(m,6H),1.47-1.07(m,5H),1.03(s,3H),0.75(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.21(C),148.42(C),140.82(C),140.17(C),132.50(q,C,2JCF＝32.5Hz),132.50(q,C,2JCF＝32.5Hz),129.39(CH),129.39(CH),126.08(d,CH,3JCF＝2.75Hz),123.55(d,C,1JCF＝270.0Hz),123.55(d,C,1JCF＝270.0Hz),121.57(CH),118.76(CH),118.76(CH),118.64(C)，111.89(d,CH,3JCF＝2.625Hz),111.89(d,CH,3JCF＝2.625Hz),110.48(CH),99.97(CH),71.76(CH),56.56(CH),50.23(CH),48.58(CH),44.57(C),42.29(CH2),38.54(CH2),38.35(CH2),37.28(CH2),36.62(C),32.38(CH),31.89(CH2),31.65(CH2),27.03(CH2),24.62(CH2),20.97(CH2),19.45(CH3),13.43(CH3)。
化合物5.10
1H-NMR(CDCl3,500MHz):δ(ppm)8.39(s,1H),8.22(d,2H,J＝9.0Hz),7.81(d,2H,J＝9.0Hz),5.38(m,1H),3.89-3.81(m,2H),3.56-3.50(m,1H),2.89-2.85(q,2H,J＝7.0Hz),2.75(t,1H,J＝10Hz),2.47-2.39(m,1H),2.32-2.22(m,2H),2.08-1.95(m,4H),1.84-1.49(m,8H),1.43-1.27(m,4H),1.24(t,3H,J＝7.0Hz),1.11-1.05(m,1H),1.00(s,3H),0.63(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)154.42(C),144.96(C),144.21(C),140.83(C),127.95(CH),125.29(CH),125.29(CH),121.48(CH),117.91(CH),117.91(CH),117.51(C),71.64(CH),56.65(CH),50.26(CH),48.32(CH),44.66(C),42.36(CH2),42.28(CH2),41.20(CH2),38.52(CH2),37.33(CH2),36.61(C),32.36(CH),31.87(CH2),31.69(CH2),26.74(CH2),24.55(CH2),20.98(CH2),19.45(CH3),13.33(CH3),12.51(CH3)。
化合物5.11
1H-NMR(CDCl3&CD3OD):δ(ppm)8.40(s,1H),8.21(d,2H,J＝9.0Hz),7.78(m,2H),5.38(m,1H),3.88-3.81(m,2H),3.75(t,2H,J＝5Hz),3.52-3,45(m,1H),2.89(t,2H,J＝5Hz)2.77(t,1H,J＝10Hz),2.44-2.40(m,1H),2.33-1.96(m,4H),1.89-1.79(m,3H),1.61-1.22(m,9H),1.22-0.97(m,5H),1.02(s,3H),0.64(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.79(C),145.89(C),144.92(C),140.51(C),126.68(CH),126.68(CH),125.38(CH),121.69(CH),120.73(CH),118.66(CH),118.66(CH),71.54(CH),59.83(CH),56.65(CH2),50.47(CH),50.49(CH2),48.54(CH),44.75(C),42.83(CH2),42.14(CH2),38.52(CH2),37.62(CH2),36.88(C),32.54(CH),32.05(CH2),31.37(CH2),26.81(CH2),24.78(CH2),21.12(CH2),19.51(CH3),13.12(CH3)。
化合物5.12
1H-NMR(CDCl3,500MHz):δ(ppm)8.28(d,2H,J＝9.0Hz),7.92(s,1H),7.80(d,2H,J＝9.0Hz),7.21(t,2H,J＝8.0Hz),6.77(t,1H,J＝7.0Hz),6.66(d,2H,J＝7.5Hz),5.38(m,1H),4.26-4.20(m,2H),3.82(s,1H),3.57-3.50(m,1H),2.82(t,1H,J＝10.0Hz),2.49-2.42(m,1H),2.33-2.22(m,2H),2.09-1.99(m,2H),1.86-1.71(m,4H),1.66-1.47(m,6H),1.44-1.09(m,5H),1.02(s,3H),0.74(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)154.36(C),147.89(C),144.79(C),144.51(C),140.81(C),129.40(CH),129.40(CH),126.03(CH),125.34(CH),125.34(CH),122.79(C),121.55(CH),118.05(CH),117.77(CH),117.77(CH),113.02(CH),113.02(CH),71.75(CH),56.61(CH),50.23(CH),48.63(CH),44.73(C),42.30(CH2),38.85(CH2),38.55(CH2),37.32(CH2),36.63(C),32.39(CH),31.89(CH2),31.65(CH2),26.91(CH2),24.63(CH2),21.03(CH2),19.46(CH3),13.49(CH3)。
化合物5.13
1H-NMR(CDCl3,500MHz):δ(ppm)8.31(d,2H,J＝9.0Hz),7.93(s,1H),7.82(d,2H,J＝9.0Hz),7.12(t,1H,J＝7.5Hz),6.60(d,1H,J＝7.0Hz),6.50-6.48(m,2H),5.40-5.39(m,1H),4.25-4.19(m,2H),3.71(s,1H),3.58-3.52(m,1H),2.83(t,1H,J＝10.0Hz),2.50-2.41(m,1H),2.36-2.24(m,5H),2.10-2.00(m,2H),1.89-1.70(m,4H),1.65-1.50(m,6H),1.46-1.08(m,5H),1.04(s,3H),0.75(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)154.37(C),147.93(C),144.76(C),144.52(C),140.80(C),139.21(C),129.27(CH),126.03(CH),125.34(CH),125.34(CH),122.90(C),121.56(CH),118.99(CH),117.76(CH),117.76(CH),113.83(CH),110.09(CH),71.74(CH),56.59(CH),50.22(CH),48.60(CH),44.71(C),42.29(CH2),38.84(CH2),38.52(CH2),37.31(CH2),36.62(C),32.38(CH),31.89(CH2),31.64(CH2),26.93(CH2),24.63(CH2),21.66(CH3),21.01(CH2),19.46(CH3),13.49(CH3)。
化合物5.14
1H-NMR(CDCl3,500MHz):δ(ppm)8.28(d,2H,J＝9.0Hz),7.92(s,1H),7.81(d,2H,J＝9.0Hz),7.15(t,1H,J＝7.5Hz),7.08(d,1H,J＝7.5Hz),6.72(t,1H,J＝7.5Hz),6.66(d,1H,J＝7.5Hz),5.38(m,1H),4.30-4.22(m,2H),3.64(s,1H),3.56-3.50(m,1H),2.83(t,1H,J＝10.0Hz),2.49-2.39(m,1H),2.33-2.22(m,2H),2.15(s,3H),2.08-1.99(m,2H),1.86-1.72(m,4H),1.63-1.51(m,6H),1.45-1.05(m,5H),1.02(s,3H),0.75(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)154.50(C),145.84(C),144.80(C),144.51(C),140.80(C),130.23(CH),127.27(CH),126.13(CH),125.34(CH),125.34(CH),122.77(C),122.15(C),121.56(CH),117.81(CH),117.81(CH),117.61(CH),109.97(CH),71.74(CH),56.58(CH),50.20(CH),48.59(CH),44.69(C),42.29(CH2),38.74(CH2),38.52(CH2),37.30(CH2),36.62(C),32.38(CH),31.88(CH2),31.64(CH2),27.01(CH2),24.64(CH2),20.98(CH2),19.46(CH3),17.56(CH3),13.50(CH3)。
化合物5.15
1H-NMR(CDCl3,500MHz):δ(ppm)8.28(d,2H,J＝9.0Hz),7.93(s,1H),7.81(d,2H,J＝9.0Hz),6.89(t,1H,J＝7.5Hz),6.80(d,1H,J＝8.0Hz),6.72(t,1H,J＝7.5Hz),6.65(d,1H,J＝8.0Hz),5.38(m,1H),4.40(s,1H),4.26-4.18(m,2H),3.85(s,3H),3.56-3.50(m,1H),2.82(t,1H,J＝10.0Hz),2.49-2.40(m,1H),2.32-1.99(m,4H),1.86-1.71(m,4H),1.56-1.43(m,6H),1.43-1.06(m,5H),1.02(s,3H),0.74(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)154.37(C),146.91(C),144.72(C),144.57(C),140.80(C),137.89(C),126.08(CH),125.33(CH),125.33(CH),122.93(C),121.56(CH),121.33(CH),117.75(CH),117.75(CH),117.14(CH),110.18(CH),109.51(CH),71.75(CH),56.60(CH),55.44(CH3),50.24(CH),48.62(CH),44.70(C),42.30(CH2),38.63(CH2),38.50(CH2),37.30(CH2),36.62(C),32.39(CH),31.89(CH2),31.65(CH2),28.94(CH2),24.89(CH2),21.03(CH2),19.46(CH3),13.49(CH3)。
化合物5.16
1H-NMR(CDCl3,500MHz):δ(ppm)8.28(d,2H,J＝9.0Hz),7.92(s,1H),7.81(d,2H,J＝9.0Hz),6.85-6.81(m,2H),6.65-6.62(m,1H),5.38(m,1H),4.26-4.20(m,2H),3.93(s,1H),3.57-3.50(m,1H),2.81(t,1H,J＝10.0Hz),2.49-2.42(m,1H),2.33-2.18(m,5H),2.14-1.96(m,2H),1.87-1.71(m,4H),1.64-1.51(m,6H),1.49-1.24(m,5H),1.02(s,3H),0.74(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)154.30(C),151.54(C,J＝237.25Hz),144.80(C),144.50(C),140.82(C),133.85(C,d,J＝11.875Hz),127.42(C,d,J＝6.5Hz),126.01(CH),125.34(CH),125.34(CH),124.85(CH,d,J＝3.0Hz),122.55(CH),121.54(C),117.80(CH),117.80(CH),115.40(CH,d,J＝18.125Hz),112.51(CH,d,J＝3.5Hz),71.74(CH),56.61(CH),50.32(CH),48.66(CH),44.70(C),42.30(CH2),38.84(CH2),38.52(CH2),37.32(CH2),36.62(C),32.38(CH),31.89(CH2),31.65(CH2),26.90(CH2),24.62(CH2),21.01(CH2),20.38(CH3),19.45(CH3),13.48(CH3)。
化合物5.17
1H-NMR(CDCl3,500MHz):δ(ppm)8.28(d,2H,J＝9.0Hz),7.91(s,1H),7.81(d,2H,J＝9.0Hz),7.05(t,1H,J＝8.0Hz),6.81(d,1H,J＝8.0Hz),6.55(d,1H,J＝8.0Hz),5.37(m,1H),4.27-4.19(m,2H),3.76(s,1H),3.56-3.47(m,1H),2.81(t,1H,J＝10.0Hz),2.49-2.38(m,1H),2.33-2.24(m,2H),2.21(s,3H),2.10-1.95(m,2H),1.89-1.70(m,6H),1.49-1.22(m,8H),1.02(s,3H),0.75(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)154.45(C),146.97(C),144.86(C),144.44(C),140.80(C),134.74(C),127.35(CH),126.13(CH),125.35(CH),125.35(CH),122.24(C),121.53(CH),119.81(C),118.59(CH),117.84(CH),117.84(CH),108.41(CH),71.73(CH),56.59(CH),50.20(CH),48.62(CH),44.70(C),42.29(CH2),38.93(CH2),38.56(CH2),37.31(CH2),36.62(C),32.38(CH),31.87(CH2),31.63(CH2),27.03(CH2),24.63(CH2),20.99(CH2),19.45(CH3),13.60(CH3),13.5(CH3)。
化合物5.18
1H-NMR(CDCl3,500MHz):δ(ppm)8.30(d,2H,J＝7.5Hz),7.93(s,1H),7.82(t,2H,J＝8.0Hz),7.21(s,1H),6.99(s,2H),5.38-5.37(m,1H),4.32-4.24(m,3H),3.58-3.50(m,1H),2.79(t,1H,J＝10.0Hz),2.50-2.42(m,1H),2.34-2.21(m,2H),2.09-2.00(m,2H),1.881.70(m,4H),1.58-1.43(m,6H),1.41-1.07(m,5H),1.03(s,3H),0.75(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)154.37(C),148.24(C),145.05(C),144.31(C),140.83(C),132.62(q,C,2JCF＝32.625Hz),132.62(q,C,2JCF＝32.625Hz),126.12(CH),125.40(CH),125.40(CH),123.50(d,C,1JCF＝270.875Hz),123.50(d,C,1JCF＝270.875Hz),121.50(CH),120.97(CH),117.96(CH),119.52(C)，112.03(d,CH,3JCF＝3.875Hz),112.03(d,CH,3JCF＝3.875Hz),110.92(m,CH),71.74(CH),56.63(CH),50.20(CH),48.66(CH),44.76(C),42.29(CH2),38.64(CH2),38.37(CH2),37.29(CH2),36.63(C),32.38(CH),31.87(CH2),31.65(CH2),27.06(CH2),24.61(CH2),20.98(CH2),19.45(CH3),13.48(CH3)。
化合物5.19
1H-NMR(CDCl3):δ(ppm)7.84(s,1H),7.60(d,2H,J＝9.0Hz),7.35(d,2H,J＝9.0Hz),5.38(m,1H),3.73-3.66(m,2H),3.53(m,1H),2.77-2.71(m,3H)2.44(m,1H),2.33-1.94(m,4H),1.87-1.62(m,8H),1.59-1.34(m,5H),1.31-1.17(m,2H),1.16(t,3H,J＝7.0Hz),1.12-1.07(m,1H),1.01(s,3H),0.68(s,3H)。
13C-NMR(CDCl3):δ(ppm)152.39(C),140.87(C),139.01(C),130.80(C),129.31(CH),129.31(CH),125.61(CH),121.59(CH),119.58(CH),119.58(CH),119.41(C),71.73(CH),56.65(CH),50.36(CH),48.52(CH),44.51(C),43.96(CH2),43.54(CH2),43.35(CH2),38.46(CH2),37.35(CH2),36.65(C),32.41(CH),31.94(CH2),31.69(CH2),26.86(CH2),24.63(CH2),21.01(CH2),19.46(CH3),15.16(CH3),13.38(CH3)。
化合物5.20
1H-NMR(CDCl3&CD3OD):δ(ppm)8.05(s,1H),7.64(d,2H,J＝9.0Hz),7.40(m,2H),5.38(m,1H),3.85-3.79(m,2H),3.75(t,2H,J＝5Hz),3.52-3,45(m,1H),2.87(t,2H,J＝5Hz)2.76(t,1H,J＝10Hz),2.48-2.40(m,1H),2.31-1.95(m,4H),1.86-1.77(m,3H),1.64-1.23(m,9H),1.24-0.96(m,5H),1.01(s,3H),0.67(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.83(C),141.12(C),138.95(C),131.54(C),129.55(CH),129.55(CH),127.03(CH),121.61(CH),120.20(CH),120.20(CH),118.86(CH),71.44(CH),59.81(CH),56.77(CH2),50.49(CH),50.47(CH2),48.58(CH),44.78(C),42.84(CH2),42.04(CH2),38.61(CH2),37.50(CH2),36.81(C),32.57(CH),32.07(CH2),31.33(CH2),26.85(CH2),24.75(CH2),21.14(CH2),19.52(CH3),13.42(CH3)。
化合物5.21
1H-NMR(CDCl3,500MHz):δ(ppm)7.79(s,1H),7.58(d,2H,J＝9.0Hz),7.36(d,2H,J＝9.0Hz),7.20(t,2H,J＝8.0Hz),6.75(t,1H,J＝7.0Hz),6.66(d,2H,J＝7.5Hz),5.37(m,1H),4.22-4.15(m,2H),3.74(s,1H),3.53(m,1H),2.80(t,1H,J＝10.0Hz),2.44(m,1H),2.32-2.21(m,2H),2.07-1.96(m,2H),1.86-1.69(m,4H),1.63-1.45(m,6H),1.43-1.06(m,5H),1.01(s,3H),0.72(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.53(C),148.08(C),140.81(C),138.88(C),131.04(C),129.35(CH),129.35(CH),129.35(CH),129.35(CH),125.83(CH),121.61(CH),120.85(C),119.68(CH),119.68(CH),117.81(CH),112.95(CH),112.95(CH),71.76(CH),56.55(CH),50.26(CH),48.54(CH),44.57(C),42.31(CH2),38.77(CH2),38.46(CH2),37.31(CH2),36.63(C),32.39(CH),31.91(CH2),31.66(CH2),26.91(CH2),24.63(CH2),21.02(CH2),19.45(CH3),13.44(CH3)。
化合物5.22
1H-NMR(CDCl3,500MHz):δ(ppm)7.79(s,1H),7.58(d,2H,J＝9.0Hz),7.36(d,2H,J＝9.0Hz),7.09(t,1H,J＝8.0Hz),6.57(d,1H,J＝7.5Hz),6.48-6.46(m,2H),5.36(m,1H),4.20-4.14(m,2H),3.68(s,1H),3.53(m,1H),2.80(t,1H,J＝10.0Hz),2.44(m,1H),2.29(s,3H),2.61-1.96(m,4H),1.86-1.69(m,4H),1.62-1.48(m,6H),1.45-1.05(m,5H),1.01(s,3H),0.72(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.56(C),148.16(C),140.83(C),139.16(C),138.90(C),131.04(C),129.37(CH),129.37(CH),129.24(CH),129.70(CH),125.85(CH),121.63(CH),120.98(C),119.70(CH),119.70(CH),118.78(CH),113.77(CH),110.07(CH),71.78(CH),56.55(CH),50.28(CH),48.53(CH),44.58(C),42.33(CH2),38.79(CH2),38.45(CH2),37.33(CH2),36.65(C),32.41(CH),31.93(CH2),31.68(CH2),26.95(CH2),24.66(CH2),21.69(CH3),21.03(CH2),19.48(CH3),13.46(CH3)。
化合物5.23
1H-NMR(CDCl3,500MHz):δ(ppm)7.80(s,1H),7.60(d,2H,J＝9.0Hz),7.37(d,2H,J＝9.0Hz),7.16(t,1H,J＝8.0Hz),7.08(d,1H,J＝7.5Hz),6.72-6.68(m,2H),5.37(m,1H),4.25-4.19(m,2H),3.57(s,1H),3.52(m,1H),2.82(t,1H,J＝10.0Hz),2.44(m,1H),2.32-2.21(m,2H),2.13(s,3H),2.07-1.96(m,2H),1.85-1.70(m,4H),1.63-1.46(m,6H),1.45-1.05(m,5H),1.01(s,3H),0.74(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.69(C),146.04(C),140.80(C),138.87(C),131.07(C),130.13(C),129.35(CH),129.35(CH),127.23(CH),125.93(CH),122.05(CH),121.60(CH),120.85(C),119.70(CH),119.70(CH),117.37(CH),109.90(CH),71.75(CH),56.52(CH),50.24(CH),48.51(CH),44.53(C),42.31(CH2),38.68(CH2),38.43(CH2),37.30(CH2),36.63(C),32.39(CH),31.90(CH2),31.65(CH2),27.03(CH2),24.64(CH2),20.97(CH2),19.45(CH3),17.55(CH3),13.45(CH3)。
化合物5.24
1H-NMR(CDCl3,500MHz):δ(ppm)7.81(s,1H),7.59(d,2H,J＝9.0Hz),7.36(d,2H,J＝9.0Hz),6.89(t,1H,J＝8.0Hz),6.80(d,1H,J＝7.5Hz),6.73-6.66(m,2H),5.38(m,1H),4.33(s,1H),4.23-4.17(m,2H),3.84(s,3H),3.53(m,1H),2.81(t,1H,J＝10.0Hz),2.45(m,1H),2.32-1.97(m,4H),1.86-1.70(m,4H),1.63-1.46(m,6H),1.43-1.05(m,5H),1.02(s,3H),0.73(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.53(C),146.88(C),140.80(C),138.93(C),138.11(C),130.94(C),129.32(CH),129.32(CH),125.88(CH),121.61(CH),121.33(CH),120.98(C),119.67(CH),119.67(CH),116.88(CH),110.13(CH),109.45(CH),71.75(CH),56.54(CH),55.41(CH3),50.28(CH),48.53(CH),44.54(C),42.31(CH2),38.56(CH2),38.40(CH2),37.30(CH2),36.62(C),32.39(CH),31.91(CH2),31.66(CH2),26.90(CH2),24.64(CH2),21.02(CH2),19.45(CH3),13.43(CH3)。
化合物5.25
1H-NMR(CDCl3,500MHz):δ(ppm)7.79(s,1H),7.58(d,2H,J＝9.0Hz),7.36(d,2H,J＝9.0Hz),6.83-6.81(m,2H),6.80-6.63(m,1H),5.37(m,1H),4.22-4.16(m,2H),3.87(s,1H),3.53(m,1H),2.79(t,1H,J＝10.0Hz),2.48-2.40(m,1H),2.32-2.21(m,5H),2.07-1.96(m,2H),1.86-1.69(m,4H),1.62-1.45(m,6H),1.43-1.05(m,5H),1.01(s,3H),0.72(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.47(C),150.57(C,J＝237.75Hz),140.82(C),138.88(C),134.09(C,d,J＝12.5Hz),131.06(C),129.34(CH),129.34(CH),127.14(C,d,J＝6.25Hz),125.80(CH),124.83(CH,d,J＝3.0Hz),121.60(CH),120.64(C),119.71(CH),119.71(CH),115.38(CH,d,J＝18.125Hz),112.49(CH,d,J＝3.60Hz),71.76(CH),56.56(CH),50.28(CH),48.59(CH),44.55(C),42.33(CH2),38.80(CH2),38.44(CH2),37.32(CH2),36.63(C),32.39(CH),31.91(CH2),31.67(CH2),26.90(CH2),24.63(CH2)(CH2),21.01(CH2),20.38(CH3),19.45(CH3),13.43(CH3)。
化合物5.26
1H-NMR(CDCl3,500MHz):δ(ppm)7.79(s,1H),7.61(d,2H,J＝9.0Hz),7.38(d,2H,J＝9.0Hz),7.06(t,1H,J＝8.0Hz),6.81(d,1H,J＝8.0Hz),6.58(d,1H,J＝8.0Hz),5.37(m,1H),4.23-4.17(m,2H),3.68(s,1H),3.52(m,1H),2.79(t,1H,J＝10.0Hz),2.44(m,1H),2.32-2.21(m,2H),2.19(s,3H),2.07-1.96(m,2H),1.85-1.68(m,4H),1.62-1.35(m,8H),1.32-1.05(m,3H),1.01(s,3H),0.73(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.66(C),147.15(C),140.80(C),138.81(C),134.67(C),131.19(C),129.38(CH),129.38(CH),127.32(CH),125.93(CH),121.58(CH),120.36(C),119.73(CH),119.73(CH),119.68(C),118.35(CH),108.32(CH),71.75(CH),56.53(CH),50.24(CH),48.54(CH),44.54(C),42.31(CH2),38.89(CH2),38.48(CH2),37.31(CH2),36.63(C),32.39(CH),31.89(CH2),31.66(CH2),27.03(CH2),24.63(CH2),20.98(CH2),19.45(CH3),13.59(CH3),13.45(CH3)。
化合物5.27
1H-NMR(CDCl3,500MHz):δ(ppm)7.80(s,1H),7.59(d,2H,J＝7.5Hz),7.38(t,2H,J＝8.0Hz),7.19(s,1H),6.79(s,2H),5.38-5.37(m,1H),4.22(s,1H),4.14-4.10(m,2H),3.56-3.50(m,1H),2.77(t,1H,J＝10.0Hz),2.48-2.40(m,1H),2.33-2.21(m,2H),2.08-1.97(m,2H),1.87-1.69(m,4H),1.63-1.48(m,6H),1.47-1.06(m,5H),1.02(s,3H),0.73(s,3H)。
13C-NMR(CDCl3,125MHz):δ(ppm)152.59(C),148.37(C),140.82(C),138.70(C),132.53(q,C,2JCF＝32.5Hz),132.53(q,C,2JCF＝32.5Hz),131.42(C),129.43(CH),129.43(CH),123.35(d,C,1JCF＝265.0Hz),123.35(d,C,1JCF＝265.0Hz),121.53(CH),119.79(CH),119.79(CH),119.62(CH),119.14(C)，111.92(d,CH,3JCF＝2.875Hz),111.92(d,CH,3JCF＝2.875Hz),110.58(m,CH),71.74(CH),56.56(CH),50.23(CH),48.57(CH),44.57(C),42.29(CH2),38.55(CH2),38.33(CH2),37.28(CH2),36.62(C),32.38(CH),31.88(CH2),31.65(CH2),27.03(CH2),24.60(CH2),20.96(CH2),19.43(CH3),13.41(CH3)。
化合物6.1
1H-NMR(CDCl3&CH3OD):δ(ppm)7.91(s,1H),7.63(d,2H,J＝8.0Hz),7.46-7.41(m,2H),7.26-7.23(m,1H),5.38(m,1H),4.63-4.56(m,2H),3.53-3.43(m,1H),3.36(s,1H),2.83(t,1H,J＝10.0Hz),2.47-2.40(m,1H),2.30-2.18(m,2H),2.08-1.96(m,2H),1.86-1.76(m,3H),1.69-1.48(m,6H),1.44-1.07(m,7H),1.01(s,3H),0.69(s,3H)。
13C-NMR(CDCl3&CH3OD):δ(ppm)152.26(C),141.15(C),140.51(C),129.50(CH),129.50(CH),126.93(CH),126.16(CH),122.74(C),121.67(CH),119.26(CH),119.26(CH),71.49(CH),56.75(CH),55.48(CH2),50.59(CH),48.90(CH),44.66(C),42.07(CH2),38.41(CH2),37.52(CH2),36.82(C),32.59(CH),32.11(CH2),31.37(CH2),26.72(CH2),24.79(CH2),21.15(CH2),19.52(CH3),13.41(CH3)。
化合物6.2
1H-NMR(CDCl3&CH3OD):δ(ppm)8.30(d,2H,J＝8.0Hz),8.06(s,1H),7.87(d,2H,J＝8.0Hz),5.38(m,1H),4.64-4.58(m,2H),3.52-3.46(m,1H),3.37(s,1H),2.81(t,1H,J＝10.0Hz),2.48-2.40(m,1H),2.31-2.21(m,2H),2.09-1.98(m,2H),1.87-1.78(m,3H),1.70-1.48(m,6H),1.43-1.07(m,7H),1.02(s,3H),0.70(s,3H)。
13C-NMR(CDCl3&CH3OD):δ(ppm)154.30(C),144.87(C),144.86(C),141.11(C),126.55(CH),125.55(CH),125.55(CH),125.00(C),121.58(CH),118.03(CH),118.03(CH),71.47(CH),56.79(CH),55.45(CH2),50.50(CH),48.79(CH),44.73(C),42.06(CH2),38.46(CH2),37.48(CH2),36.78(C),32.54(CH),32.05(CH2),31.36(CH2),26.78(CH2),24.74(CH2),21.12(CH2),19.51(CH3),13.48(CH3)。
化合物6.3
1H-NMR(CDCl3&CH3OD):δ(ppm)7.89(s,1H),7.61(d,2H,J＝9.0Hz),7.39(d,2H,J＝9.0Hz),5.37(m,1H),4.62-4.55(m,2H),3.52-3.44(m,1H),2.81(t,1H,J＝10.0Hz),2.46-2.38(m,1H),2.31-2.21(m,2H),2.08-1.96(m,2H),1.86-1.76(m,3H),1.69-1.48(m,5H),1.43-1.09(m,7H),1.01(s,3H),0.68(s,3H)。
13C-NMR(CDCl3&CH3OD):δ(ppm)152.58(C),141.14(C),139.09(C),131.37(C),129.52(CH),129.52(CH),126.70(CH),123.20(C),121.64(CH),120.20(CH),120.20(CH),71.48(CH),56.75(CH),55.43(CH2),50.56(CH),48.89(CH),44.65(C),42.06(CH2),38.41(CH2),37.51(CH2),36.81(C),32.58(CH),32.09(CH2),31.36(CH2),26.74(CH2),24.77(CH2),21.14(CH2),19.51(CH3),13.42(CH3)。
实施例三
式(I)吡唑基甾体衍生物的抗肿瘤细胞增殖活性，通过初步试验得出，其癌细胞毒性IC50值均未超过6uM。本实施例挑选了几个化合物，并进行生物活性评价。
本实施例采用RSB法测定本发明式(I)的吡唑基甾体衍生物对A549(人肺腺癌细胞)、Hela(子宫颈癌细胞系)、HepG2(人肝癌细胞)三种肿瘤细胞的增殖抑制活性。
具体方法：
准确称量待测化合物1-3mg，以DMSO为溶剂，配制成浓度为10mMol/L的溶液，室温下静置半小时待样品完全溶解后保存待用。
取处于对数生长期的A549、Hela、HepG2细胞，清洗并用胰酶消化后制成细胞悬液，细胞计数并稀释至适当浓度，将细胞悬液均匀的加入96孔板中，每孔100ul，每组设置三个重复，同时设置阴性对照和阳性对照孔。取一定量的事先配置好的待测化合物加入到96孔板中，化合物从50uM起，3倍梯度稀释，共9个梯度，然后将处理好的细胞置于5％二氧化碳浓度，37℃培养箱中培养72h。培养时间过后，终止培养，移去上清液，每个孔加入冷的10％TCA100ul，4℃条件下固定2h，用二次蒸馏水反复冲洗5次，50℃烘箱中烘干约半小时。待其干燥后，加入冰醋酸配制的SRB溶液100ul，室温染色半小时后用1％冰醋酸冲洗5次以除去非特异性结合的染料，此步需要操作迅速以防止已经与蛋白特异性结合的染料分解。50℃烘箱烘干半小时，加150ul Tris溶液溶解拍打混匀，酶标仪A540nm测定吸光度，计算其抑制率，用EXCEl计算其IC50，结果见表1。
表1 部分化合物抗细胞增殖活性IC50(μmol/L)
表1的结果说明，以抗癌药物顺铂作为对照药品，吡唑基甾体衍生物(化合物5.1、5.10、5.19和6.1)对A549(人肺腺癌细胞)、Hela(子宫颈癌细胞系)、HepG2(人肝癌细胞)三种肿瘤细胞有很好的细胞毒性，对三种癌细胞的毒性优于顺铂。
为了进一步客观评价吡唑基甾体衍生物的癌细胞毒性，本实施例还以紫杉醇作为对照药品，采用相同的试验方法，获得的试验数据见表2。
表2 部分化合物抗细胞增殖活性IC50(μmol/L)
表2的结果说明，以紫杉醇作为对照药品，吡唑基甾体衍生物(化合物5.1、6.1、和6.2)对A549(人肺腺癌细胞)、Hela(子宫颈癌细胞系)、HepG2(人肝癌细胞)三种肿瘤细胞的细胞毒性不及紫杉醇。
通过本实施例可以初步推测，本发明式(I)吡唑基甾体衍生物的抗肿瘤细胞增殖活性介于紫杉醇和顺铂之间，具有进一步研究开发的前景。
上面结合实施例对本发明做了进一步的叙述，但本发明并不限于上述实施方式，在本领域的普通技术人员所具备的知识范围内，还可以在不脱离本发明宗旨的前提下做出各种变化。

Claims (9)

1.吡唑基甾体衍生物，其特征在于，具有式(Ⅰ)的化学结构：
其中，取代基R1代表氢、硝基或卤素；取代基R2代表C1-C6烷基、羟基取代的C1-C6烷基、单取代或多取代芳香基。
2.根据权利要求1所述的吡唑基甾体衍生物，其特征在于，所述取代基R2为C1-C6直链烷基、羟基取代的C1-C6直链烷基、单取代或多取代苯基。
3.根据权利要求2所述的吡唑基甾体衍生物，其特征在于，所述取代基R2为C1-C3直链烷基、羟基取代的C1-C3直链烷基、单取代或具有两个取代基的苯基。
4.根据权利要求3所述的吡唑基甾体衍生物，其特征在于，所述取代基R1为氢、硝基、或氯；取代基R2为乙基、2-羟乙基、邻甲基苯基、间甲基苯基、邻甲氧基苯基、2-氟对甲基苯基、3-氯-2-甲基苯基或3,5-三氟甲基苯基。
5.根据权利要求1所述的吡唑基甾体衍生物，其特征在于，具有下述结构：
6.具有式(Ⅰ)结构的吡唑基甾体衍生物的制备方法，采用如下的反应路线：
7.药物组合物，包含权利要求1至5中任一项所述的吡唑基甾体衍生物，以及药学上可接受的赋形剂或载体。
8.权利要求1至5中任一项所述的吡唑基甾体衍生物在制备抗癌药物中的用途。
9.根据权利要求8所述的用途，所述抗癌药物用于抑制人肺腺癌细胞、子宫颈癌细胞系或人肝癌细胞的活性。
CN201510363783.4A 2015-06-26 2015-06-26 吡唑基甾体衍生物及其制备方法、用途 Expired - Fee Related CN104910236B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510363783.4A CN104910236B (zh) 2015-06-26 2015-06-26 吡唑基甾体衍生物及其制备方法、用途

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510363783.4A CN104910236B (zh) 2015-06-26 2015-06-26 吡唑基甾体衍生物及其制备方法、用途

Publications (2)

Publication Number Publication Date
CN104910236A true CN104910236A (zh) 2015-09-16
CN104910236B CN104910236B (zh) 2016-08-17

Family

ID=54079724

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510363783.4A Expired - Fee Related CN104910236B (zh) 2015-06-26 2015-06-26 吡唑基甾体衍生物及其制备方法、用途

Country Status (1)

Country Link
CN (1) CN104910236B (zh)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106866773A (zh) * 2017-02-14 2017-06-20 西北农林科技大学 一组具有抗癌活性吡唑基甾体衍生物的制备方法及应用
CN107722101A (zh) * 2017-11-03 2018-02-23 郑州大学 甾体吡啶类衍生物及其制备方法和应用
CN114751954A (zh) * 2022-05-06 2022-07-15 长治学院 一种甾体衍生物及其制备方法和应用、抗肿瘤药物组合物
CN115073547A (zh) * 2022-06-17 2022-09-20 长治学院 一种甾体咔啉衍生物及其制备方法和应用、抗肿瘤药物组合物

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA759942A (en) * 1967-05-30 Harnik Marcel Fluorinated steroid pyrazoles
WO2014169833A1 (en) * 2013-04-17 2014-10-23 Sage Therapeutics, Inc. 19-nor c3,3-disubstituted c21-n-pyrazolyl steroids and methods of use thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA759942A (en) * 1967-05-30 Harnik Marcel Fluorinated steroid pyrazoles
WO2014169833A1 (en) * 2013-04-17 2014-10-23 Sage Therapeutics, Inc. 19-nor c3,3-disubstituted c21-n-pyrazolyl steroids and methods of use thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ABID H. BANDAY，ET AL.: "Steroidal pyrazolines and pyrazoles as potential 5a-reductase inhibitors: Synthesis and biological evaluation", 《STEROIDS》, vol. 92, 30 September 2014 (2014-09-30), pages 13 - 19, XP 029098096, DOI: doi:10.1016/j.steroids.2014.09.004 *
ABID H. BANDAY，ET AL.: "Studies on novel D-ring substituted steroidal pyrazolines as potential anticancer agents", 《STEROIDS》, vol. 75, 4 March 2010 (2010-03-04), pages 805 - 809, XP 027221095 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106866773A (zh) * 2017-02-14 2017-06-20 西北农林科技大学 一组具有抗癌活性吡唑基甾体衍生物的制备方法及应用
CN107722101A (zh) * 2017-11-03 2018-02-23 郑州大学 甾体吡啶类衍生物及其制备方法和应用
CN114751954A (zh) * 2022-05-06 2022-07-15 长治学院 一种甾体衍生物及其制备方法和应用、抗肿瘤药物组合物
CN115073547A (zh) * 2022-06-17 2022-09-20 长治学院 一种甾体咔啉衍生物及其制备方法和应用、抗肿瘤药物组合物
CN115073547B (zh) * 2022-06-17 2023-08-25 长治学院 一种甾体咔啉衍生物及其制备方法和应用、抗肿瘤药物组合物

Also Published As

Publication number Publication date
CN104910236B (zh) 2016-08-17

Similar Documents

Publication Publication Date Title
CN104910236B (zh) 吡唑基甾体衍生物及其制备方法、用途
WO2013000286A1 (zh) 蟾毒配基衍生物及其制备方法、包含该衍生物的组合物、及其用途
WO2012175044A1 (zh) 用于肿瘤治疗的水溶性铂配合物及其制备方法
CN105254631B (zh) 一种具有抗肿瘤性能的苦参碱衍生物
CN105037474A (zh) 4′-氨基-4′-去羟基-欧夹竹桃苷和4′-氨基-4′-去羟基-夹竹苷a及其用途
CN110483608A (zh) 沙蟾毒精衍生物及其制备方法、包含该衍生物的组合物、及其用途
CN110041375A (zh) 具有不对称单取代萘酰亚胺四价铂结构的化合物、制备方法及其在制备抗肿瘤药物中的应用
CN104080335B (zh) 某些化学实体、组合物及方法
Guo et al. Ginsengenin derivatives synthesized from 20 (R)-panaxotriol: Synthesis, characterization, and antitumor activity targeting HIF-1 pathway
CN108026141A (zh) 孤儿核受体Nur77的配体及其用途
Huang et al. Straightforward synthesis of steroidal selenocyanates through oxidative umpolung selenocyanation of steroids and their antitumor activity
CN116217582A (zh) 一种鹤氏唐松草碱衍生物及应用
Li et al. Diorganotin (IV) derivatives of substituted N-hydroxybenzamides with selective cytotoxicity in vitro and potent antitumor activity in vivo
CN110092789B (zh) 一种吲哚并[2,3-b]咔唑衍生物及其应用
CN108794516A (zh) 硼酸和硼酸酯类化合物及其制备方法和用途
CN111777577A (zh) 一类紫杉醇衍生物及其在制备防治人恶性肿瘤药物中的用途
CN111018772A (zh) 一类具有抗肿瘤活性的5-磺酰胺基取代的靛红类衍生物
JP2022517885A (ja) シクロブタンジカルボン酸白金錯体、その中間体、その製造方法、医薬組成物及び使用
CN109400595A (zh) 一类含噻吩环的抗癌化合物
CN110590779B (zh) 3，10二对氯苯基6，12二氮杂四高立方烷类化合物及其合成方法、应用和药物组合物
CN110078768B (zh) 锝-99m标记的含HYNIC的帕博西尼衍生物及制备方法和应用
CN106883282B (zh) 救必应酸衍生物在制备抗肿瘤的药物中的应用
CN113004268B (zh) 一种抑制肿瘤细胞生长的噻唑化合物及其用途
CN115073547B (zh) 一种甾体咔啉衍生物及其制备方法和应用、抗肿瘤药物组合物
CN109762044B (zh) 含靛红单元的甾体衍生物及其制备方法和用途

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20160817

Termination date: 20200626

CF01 Termination of patent right due to non-payment of annual fee