CN106749422B - 四苯基卟啉芳基钌化合物及其制备方法和用途 - Google Patents
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- YNHJECZULSZAQK-UHFFFAOYSA-N tetraphenylporphyrin Chemical compound C1=CC(C(=C2C=CC(N2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3N2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 YNHJECZULSZAQK-UHFFFAOYSA-N 0.000 claims description 13
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Abstract
本发明公开了一种四苯基卟啉芳基钌化合物及其制备方法和用途。本发明的四苯基卟啉芳基钌化合物可用于制备治疗癌症的药物，可制成注射剂、片剂、丸剂、胶囊剂、悬浮剂或乳剂的形式使用。本发明四苯基卟啉芳基钌化合物的制备方法简单，原料易得，具有成本低的优势。
Description
技术领域
本发明涉及一种本发明涉及一种四苯基卟啉-2-(6-(2-连二吡啶)乙醚芳基钌及制备方法和用途，尤其涉及一氯一四苯基卟啉-2-(6-(2-连二吡啶)乙醚一甲基异丙基苯合钌(II)及制备方法和用途。
背景技术
目前，顺铂已成为世界上用于治疗癌症最为广泛的3种药物之一，在美国的年销售额达到近5亿美元。但顺铂的使用也存在有一定的不足，它对某些肿瘤没有抑制作用，且易与其他铂制剂产生交叉耐药性。此外，顺铂有多种副作用，如肾毒性、外周神经毒性、骨髓毒性、血液学毒性以及催吐性等。因此，寻找高效、低毒且无交叉耐药性的新型抗肿瘤药物一直是科研工作者的研究热点。
芳基钌配合物由于其毒性低，抗肿瘤活性高的特点而受到人们的关注。卟啉类化合物由于其稳定无毒的性质，以及其良好的发光性能而令人瞩目。以卟啉类化合物芳基钌配合物结合得到卟啉连芳基钌钌化合物，由于芳基钌与卟啉化合物的协同作用，能够使其在具备良好抗肿瘤活性的基础上具备光毒性，达到增强其细胞抑制活性的效果。
发明内容
针对上述技术问题，本发明提供了一种四苯基卟啉芳基钌化合物，其可用于制备治疗癌症的药物。
本发明的另一个目的是提供一种四苯基卟啉芳基钌化合物的制备方法，方法简单，原料易得，成本低。
本发明的又一个目的是提供一种四苯基卟啉芳基钌化合物的用途。
本发明提供的技术方案为：
一种四苯基卟啉芳基钌化合物，其为一氯一四苯基卟啉-2-(6-(2-连二吡啶)乙醚一甲基异丙基苯合钌(II)；其结构式：
优选的是，所述的四苯基卟啉芳基钌化合物的制备方法，包括：
1)将0.366g钌重量含量为37％的RuCl3·xH2O和3ml纯度为95％的γ-松油烯溶于10ml无水乙醇，加热回流搅拌6小时，静置析出得到二氯化二氯-二-甲基异丙基苯合二钌(II)；
2)称取0.095g一硝基-四苯基卟啉,0.12g 2-(6-(2-连二吡啶)乙醇,溶于10mlDMF溶液，氮气保护下80℃反应8小时后，静置析出得到四苯基卟啉-2-(6-(2-连二吡啶)乙醚；
3)将20mg的四苯基卟啉-2-(6-(2-连二吡啶)乙醚和12mg二氯化二氯-二-甲基异丙基苯合二钌(II)溶于8ml无水乙醇，加热搅拌回流6小时，反应完成后把溶液蒸发剩2ml液体，加入30ml正己烷，析出红色晶体，即为产物一氯一四苯基卟啉-2-(6-(2-连二吡啶)乙醚一甲基异丙基苯合钌(II)。
优选的是，所述的四苯基卟啉芳基钌化合物的用途中，利用所述四苯基卟啉芳基钌化合物制备用于治疗卵巢癌的药物。
本发明的有益效果：
1、本发明的四苯基卟啉芳基钌化合物可用于制备治疗癌症的药物，可制成注射剂、片剂、丸剂、胶囊剂、悬浮剂或乳剂的形式使用。
2、本发明四苯基卟啉芳基钌化合物的制备方法简单，原料易得，具有成本低的优势。
具体实施方式
下面对本发明做进一步的详细说明，以令本领域技术人员参照说明书文字能够据以实施。
实施例一
一种四苯基卟啉芳基钌化合物，其为一氯一四苯基卟啉-2-(6-(2-连二吡啶)乙醚一甲基异丙基苯合钌(II)；其结构式：
一氯一四苯基卟啉-2-(6-(2-连二吡啶)乙醚一甲基异丙基苯合钌(II)的理化性质为：红色晶体，易溶于水和有机溶剂，其核磁共振氢谱数据为1H NMR:(ppm,CDCl3)δ＝1.31(6H,d,J＝6.2Hz),2.36(3H,s),3.15(1H,m,J＝6.3Hz),5.10(2H,s),5.20-6.50(8H,m,J＝5.9Hz),6.70-7.20(23H,m,J＝6.0Hz),7.40-8.70(7H,m,J＝5.9Hz)。
实施例二
实施例一所述的四苯基卟啉芳基钌化合物的制备方法，包括：
1)将0.366g钌重量含量为37％的RuCl3·xH2O和3ml纯度为95％的γ-松油烯溶于10ml无水乙醇，加热回流搅拌6小时，静置析出得到二氯化二氯-二-甲基异丙基苯合二钌(II)；
2)称取0.095g一硝基-四苯基卟啉,0.12g 2-(6-(2-连二吡啶)乙醇,溶于10mlDMF溶液，氮气保护下80℃反应8小时后，静置析出得到四苯基卟啉-2-(6-(2-连二吡啶)乙醚；
3)将20mg的四苯基卟啉-2-(6-(2-连二吡啶)乙醚和12mg二氯化二氯-二-甲基异丙基苯合二钌(II)溶于8ml无水乙醇，加热搅拌回流6小时，反应完成后把溶液蒸发剩2ml液体，加入30ml正己烷，析出红色晶体，即为产物一氯一四苯基卟啉-2-(6-(2-连二吡啶)乙醚一甲基异丙基苯合钌(II)。
实施例三
实施例一中所述的四苯基卟啉芳基钌化合物的用途中，利用所述四苯基卟啉芳基钌化合物制备用于治疗卵巢癌的药物。
采用MTT方法，进行体外细胞毒性测定。将实施例1得到的四苯基卟啉芳基钌化合物与胃癌SGC 7901细胞株分别作用时间72小时，结果如表1所示。
表1四苯基卟啉芳基钌化合物对肿瘤细胞株的半数有效浓度(IC50)
| 细胞株 | A2780(避光) | A2780(光照) |
| IC<sub>50</sub>(umol/mL) | 8.0±1.5 | 1.2±0.2 |
从表1的结果可以看出，本发明的四苯基卟啉芳基钌化合物经体外抗肿瘤实验表明，该化合物具有强的抗肿瘤活性以及较好的细胞光毒性。
尽管本发明的实施方案已公开如上，但其并不仅仅限于说明书和实施方式中所列运用，它完全可以被适用于各种适合本发明的领域，对于熟悉本领域的人员而言，可容易地实现另外的修改，因此在不背离权利要求及等同范围所限定的一般概念下，本发明并不限于特定的细节。
Claims (3)
1.一种四苯基卟啉芳基钌化合物，其特征在于，其结构式为：
2.如权利要求1所述的四苯基卟啉芳基钌化合物的制备方法，其特征在于，包括：
1)将0.366g钌重量含量为37％的RuCl3·xH2O和3ml纯度为95％的γ-松油烯溶于10ml无水乙醇，加热回流搅拌6小时，静置析出得到式II所示化合物；
2)称取0.095g 5,10,15-三苯基-20-对硝基苯基卟啉,0.12g 2-(6-(2-连二吡啶)乙醇,溶于10ml DMF溶液，氮气保护下80℃反应8小时后，静置析出得到式III所示化合物；
3)将20mg的四苯基卟啉-2-(6-(2-连二吡啶)乙醚和12mg二氯化二氯-二-甲基异丙基苯合二钌(II)溶于8ml无水乙醇，加热搅拌回流6小时，反应完成后把溶液蒸发剩2ml液体，加入30ml正己烷，析出红色晶体，即为产物。
3.如权利要求1所述的四苯基卟啉芳基钌化合物的用途，其特征在于，利用所述四苯基卟啉芳基钌化合物制备用于治疗卵巢癌的药物。
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| CN101851256A (zh) * | 2010-04-30 | 2010-10-06 | 广东药学院 | 一种以柔性碳链联接的钌(ⅱ)卟啉配合物及其制备方法和应用 |
| CN103724362A (zh) * | 2013-12-30 | 2014-04-16 | 重庆大学 | 对苯二甲酸桥联分子钳系列卟啉化合物及其制备方法 |
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| CN103724362A (zh) * | 2013-12-30 | 2014-04-16 | 重庆大学 | 对苯二甲酸桥联分子钳系列卟啉化合物及其制备方法 |
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