CN104030964B - 双吲哚类化合物及合成方法 - Google Patents
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Abstract
本发明涉及一种双吲哚类化合物及合成方法，其中2,2ˊ-二(3,3ˊ-N-苄基-3-1H-吲哚基丙酰胺)苯基甲烷，2,2ˊ-二(3,3ˊ-N-苄基-3-1H-吲哚基丙酰胺)对硝基苯基甲烷，2,2ˊ-二(3,3ˊ-N-苄基-3-1H-吲哚基丙酰胺)对氟苯基甲烷，2,2ˊ-二(3,3ˊ-N-苄基-3-1H-吲哚基丙酰胺)对甲氧基苯基甲烷对人白血病细胞(K562)肿瘤细胞有着一定的生长抑制作用，其IC50值分别为56.19μM，90.71μM，58.55μM，67.22μM，分析结果表明苯环对位连有弱吸电基与间位连有供电基的分子结构活性较好。
Description
技术领域
本发明属于化合物研发领域，尤其是一种双吲哚类化合物及合成方法。
背景技术
双吲哚甲烷和双吲哚乙烷是重要的吲哚衍生物。在女性和男性体内，对于提升有益的雌性激素代谢，双吲哚甲烷(BIMs)是最活泼的十字花科的物质。BIMs增加体内荷尔蒙的自然代谢，并且提高有益的雌激素(2-羟基雌激素)代谢。吲哚抗氧化剂对于缓解纤维肌痛是获专利的。BIMs在预防癌症方面也是有效的，因为它能够调节由于雌激素代谢因其的某些癌症。科学家们已经证明，BIMs诱导在人体癌细胞中的细胞凋亡，并且能使与宫颈非典型增生有关的异常细胞生长正规化。因此，吲哚及其衍生物已经成为研究方向的主题。
双吲哚类衍生物作为杂环化合物一种重要的类别所为人知晓，并且是研发和制药工业具有生物活性的中间产品。因此，对于这些化合物的制备，温和且环境友好的合成方法的发展，在制药和有机合成方面也显得尤为重要。
发明内容
本发明的目的在于提供一种双吲哚类化合物及合成方法，本发明制备的四种化合物对人白血病细胞(K562)肿瘤细胞有着一定的生长抑制作用，其IC50值分别为56.19μM，90.71μM，58.55μM，67.22μM，对人肝癌细胞(HepG2)和人结肠癌细胞(HT-29)均无抑制作用，分析结果表明苯环对位连有弱吸电基与间位连有供电基的分子结构活性较好。
本发明实现目的的技术方案是：
一种双吲哚类化合物，所述化合物名称为2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)苯基甲烷。
一种双吲哚类化合物，所述化合物名称为2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对硝基苯基甲烷。
一种双吲哚类化合物，所述化合物名称为2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对氟苯基甲烷。
一种双吲哚类化合物，所述化合物名称为2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对甲氧基苯基甲烷。
双吲哚类化合物在制备抑制肿瘤生长药物中的应用。
而且，所述肿瘤药物为人白血病细胞K562肿瘤。
本发明的优点和积极效果是：
本申请通过实验发现Pictet-Spengler反应条件亦可以生成双吲哚的结构，且具有一定的生物活性。其中2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)苯基甲烷(化合物A1)，2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对硝基苯基甲烷(化合物A2)，2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对氟苯基甲烷(化合物A3)，2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对甲氧基苯基甲烷(化合物A4)对人白血病细胞(K562)肿瘤细胞有着一定的生长抑制作用，其IC50值分别为56.19μM，90.71μM，58.55μM，67.22μM，对人肝癌细胞(HepG2)和人结肠癌细胞(HT-29)均无抑制作用，分析结果表明苯环对位连有弱吸电基与间位连有供电基的分子结构活性较好。
附图说明
图1为化合物A1氢谱图；
图2为化合物A2氢谱图；
图3为化合物A3氢谱图；
图4为化合物A4氢谱图.
具体实施方式
下面详细叙述本发明的实施例，需要说明的是，本实施例是叙述性的，不是限定性的，不能以此限定本发明的保护范围。
一、双吲哚类化合物的合成路线
反应条件：(I)AlCl3，CH2Cl2，C4H5ClO3，35℃，4h(II)EG，H6N2O，KOH，A40℃，2h(III)Et3N，THF，C3H5ClO2，Benzylamine，r.t.，1.5h(IV)C3BiF9O9S3，C6H5CHO,C7H4Cl2O，CH3OC6H4CHO，C7H7CHO，C7H5NO3，C7H5FO，34℃，3h
利用以上路线合成化合物见表1
表1双吲哚类化合物及其衍生物的命名和结构式
实施例1
2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)苯基甲烷(化合物A1)的合成
将N-苄基-1H-3-吲哚基-丙酰胺(100mg，0.38mmol)溶于乙腈溶液(15mL)中,将三氟甲磺酸铋(94.3mg，0.14mmol)和苯甲醛(88.6mg，0.84mmol)于34℃下反应3h，TLC检测反应完全后，将水(50mL)加入上述反应溶液中，EA(50mL×3)萃取合并有机相，干燥，浓缩，柱层析得到白色固体(338mg)2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)苯基甲烷，收率67％。
实施例2
2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对硝基苯基甲烷(化合物A2)的合成
将N-苄基-1H-3-吲哚基-丙酰胺(100mg，0.38mmol)溶于乙腈溶液(15mL)中,将三氟甲磺酸铋(94.3mg，0.14mmol)和对硝基苯甲醛(1.47g，0.84mmol)于34℃下反应3h，TLC检测反应完全后，将水(50mL)加入上述反应溶液中，EA(50mL×3)萃取合并有机相，干燥，浓缩，柱层析得到白色固体(330mg)2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对硝基苯基甲烷，收率75％。
实施例3
2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对氟苯基甲烷(化合物A3)的合成
将N-苄基-1H-3-吲哚基-丙酰胺(100mg，0.38mmol)溶于乙腈溶液(15mL)中,将三氟甲磺酸铋(94.3mg，0.14mmol)和对氟苯甲醛(104.3mg，0.84mmol)于34℃下反应3h，TLC检测反应完全后，将水(50mL)加入上述反应溶液中，EA(50mL×3)萃取合并有机相，干燥，浓缩，柱层析得到白色固体(303mg)2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对氟苯基甲烷，收率72％。
实施例4
2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对甲氧基苯基甲烷(化合物A4)的合成
将N-苄基-1H-3-吲哚基-丙酰胺(100mg，0.36mmol)溶于乙腈溶液(15mL)中,将三氟甲磺酸铋(94.3mg，0.14mmol)和对甲氧基苯甲醛(114.37mg，0.84mmol)于34℃下反应3h，TLC检测反应完全后，将水(50mL)加入上述反应溶液中，EA(50mL×3)萃取合并有机相，干燥，浓缩，柱层析得到白色固体(280.2mg)2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对甲氧基苯基甲烷，收率58％。
二、化合物的活性测试方法
双吲哚化合物进行了体外肿瘤细胞抑制活性的测试，所选用生物三种肿瘤细胞分别是人肝癌细胞(HepG2)、人白血病细胞(K562)和人结肠癌细胞(HT-29)。通过化合物在不同浓度下肿瘤细胞的存活率，可以计算出化合物抑制肿瘤细胞生长的IC50值，从而反映化合物抑制肿瘤细胞生长活性的高低，IC50值越小，说明化合物抑制肿瘤细胞生长活性越高。
三、体外肿瘤细胞抑制活性测试结果及分析
对目标化合物进行了体外肿瘤细胞抑制活性测试，活性测试选用了三种癌细胞：人白血病细胞K562，人肝癌细胞HepG2，人结肠癌细胞HT-29。此实验结果为本课题组其他人员测定，测试结果见表2。
表2双吲哚衍生物对肿瘤细胞的抑制活性
由表3-1可以看出，双吲哚类化合物对于人肝癌细胞HepG2，人结肠癌细胞HT-29没有抑制活性，IC50值均大于100μM，对于人白血病细胞K562，化合物A1，化合物A2，化合物A3和化合物A4有中等抑制活性，IC50值分别为56.19μM，90.71μM，58.55μM，67.22μM。从以上数据可以看出，苯环对位连有弱吸电基与间位连有供电基的分子生物活性较好。由于氟原子的原子核与氢原子的原子核大小相似，即化合物A1与化合物A3的电子效应类似，因此苯环对位连有氟原子与苯环上无供电基的IC50值类似。化合物A2的IC50值为90.71μM，接近100μM，可忽略不计。
在实验中发现Pictet-Spengler反应条件亦可以生成双吲哚的结构，且具有一定的生物活性。其中2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)苯基甲烷(化合物A1)，2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对硝基苯基甲烷(化合物A2)，2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对氟苯基甲烷(化合物A3)，2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对甲氧基苯基甲烷(化合物A4)对人白血病细胞(K562)肿瘤细胞有着一定的生长抑制作用，其IC50值分别为56.19μM，90.71μM，58.55μM，67.22μM，对人肝癌细胞(HepG2)和人结肠癌细胞(HT-29)均无抑制作用。分析结果表明苯环对位连有弱吸电基与间位连有供电基的分子结构活性较好。
Claims (5)
1.一种双吲哚类化合物，其特征在于：所述化合物名称为2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)苯基甲烷。
2.一种双吲哚类化合物，其特征在于：所述化合物名称为2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对硝基苯基甲烷。
3.一种双吲哚类化合物，其特征在于：所述化合物名称为2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对氟苯基甲烷。
4.一种双吲哚类化合物，其特征在于：所述化合物名称为2,2'-二(3,3'-N-苄基-3-1H-吲哚基丙酰胺)对甲氧基苯基甲烷。
5.权利要求1-4之一的双吲哚类化合物在制备抑制肿瘤生长药物中的应用，所述肿瘤为人白血病细胞K562肿瘤。
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1268134A (zh) * | 1997-06-25 | 2000-09-27 | 罗赫诊断器材股份有限公司 | 具有抗转移活性的双吲哚衍生物、其制备方法和含有它们的药物组合物 |
| WO2004018475A2 (en) * | 2002-08-20 | 2004-03-04 | Sri International | Analogs of indole-3-carbinol metabolites as chemotherapeutic and chemopreventive agents |
| CN102146081A (zh) * | 2010-02-09 | 2011-08-10 | 首都医科大学 | 吲哚乙酸衍生物及其制备方法和应用 |
| US20110301151A1 (en) * | 2005-02-25 | 2011-12-08 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| CN103450067A (zh) * | 2012-05-29 | 2013-12-18 | 首都医科大学 | 乙基连接的双吲哚-3-基-乙酰氨基酸、其制备、抗血栓作用和应用 |
| CN103539722A (zh) * | 2012-07-10 | 2014-01-29 | 永光制药有限公司 | 芳基取代甲基连接的双吲哚乙酸衍生物及其制备方法和应用 |
-
2014
- 2014-06-05 CN CN201410246013.7A patent/CN104030964B/zh active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1268134A (zh) * | 1997-06-25 | 2000-09-27 | 罗赫诊断器材股份有限公司 | 具有抗转移活性的双吲哚衍生物、其制备方法和含有它们的药物组合物 |
| WO2004018475A2 (en) * | 2002-08-20 | 2004-03-04 | Sri International | Analogs of indole-3-carbinol metabolites as chemotherapeutic and chemopreventive agents |
| US20110301151A1 (en) * | 2005-02-25 | 2011-12-08 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| CN102146081A (zh) * | 2010-02-09 | 2011-08-10 | 首都医科大学 | 吲哚乙酸衍生物及其制备方法和应用 |
| CN103450067A (zh) * | 2012-05-29 | 2013-12-18 | 首都医科大学 | 乙基连接的双吲哚-3-基-乙酰氨基酸、其制备、抗血栓作用和应用 |
| CN103539722A (zh) * | 2012-07-10 | 2014-01-29 | 永光制药有限公司 | 芳基取代甲基连接的双吲哚乙酸衍生物及其制备方法和应用 |
Non-Patent Citations (4)
| Title |
|---|
| cient synthesis of bis(indolyl)methanes in water,and synthesis of di-,tri-,and tetra(bis-indolyl)methanes under thermal conditions catalyzed by oxalic acid dihydrate.《Mol Divers》.2009,第14卷87-96. * |
| Indole-3-carbinol activates the cyclin-dependent kinase inhibitor p15INK4b gene;Youichirou Matsuzaki等;《Federation of European Biochemical Societies》;20040915;第576卷;137-140 * |
| Ramin Ghorbani-Vaghei.A practical and effi * |
| Zeolite catalyzed electrophilic substitution reaction of indoles with aldehydes: synthesis of bis(indolyl)methanes;M.Karthik等;《Catalysis Communications》;20040601;第5卷;371-375 * |
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