CN110922349B - 一种抗肿瘤化合物的合成及其在多发性骨髓瘤中的应用 - Google Patents
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Abstract
本发明涉及一种抗肿瘤药如式Ⅰ所示及其在肿瘤治疗药物中的应用，属于抗肿瘤药学技术范围。本发明解决的技术问题是提供一种肿瘤抑制剂的化合物。该化合物包括如下所示的化合物及其在药学上可接受的盐，可以作为一种肿瘤抑制剂，具有一定的抗肿瘤活性。式Ⅰ
Description
技术领域
本发明公开一种新型抗肿瘤药的合成以及在肿瘤治疗中的应用，研究表明，该化合物对人骨髓瘤细胞U266具有较好的抑制作用，属于肿瘤治疗药物发现的技术领域，为***药开发提供依据。
背景技术
多发性骨髓瘤（MM）是一种恶性浆细胞病，属于B淋巴细胞淋巴瘤的范围，其肿瘤细胞起源于骨髓中的浆细胞，而浆细胞是B淋巴细胞发育到最终功能阶段的细胞。其特征为骨髓浆细胞异常增生伴有单克隆免疫球蛋白或轻链（M蛋白）过度生成，极少数患者可以是不产生M蛋白的未分泌型MM。临床表现多样，主要有贫血、骨痛、肾功能不全、感染、出血、神经症状、高钙血症、淀粉样变等。据统计多发性骨髓瘤发病率估计为2～3/10万，男女比例为1.6：1，40岁以上，特别是60岁以上的老年人为多发群体。
随着生物化学、分子生物学和细胞遗传学等学科的发展，越来越多的新的靶向多发性骨髓治疗的药物已经被识别并开始应用于临床取得了可喜的成果。目前，硼替佐米，伊沙佐米是临床上最广泛的靶向药。尽管如此，多发性骨髓瘤(MM)仍是一种不能治愈的血液***肿瘤。多发性骨髓瘤患者多数为不能耐受强烈化疗中老年人，而目前应用的药物大多为化学药剂。这些药物不仅对身体有毒副作用还引起药物耐药。因此，开发靶向性的新型小分子精准治疗药物是克服MM临床问题的关键，也是未来发展的趋势和热点。
本发明涉及的化合物是一个全新骨架化合物，该化合物拥有全新的骨架类型，目前没有关于活性的报道，对于本发明涉及的化合物在制备抑制U266细胞 (多发性骨髓瘤)，但不限于U266细胞，抗肿瘤作用属于首次公开，而且由于骨架类型属于全新的骨架类型，不存在由其他化合物给出任何启示的可能，具备突出的实质性特点，同时用于多发性骨髓瘤(U266细胞)的抑制显然具有显著效果。
发明内容
本发明解决的问题是提供一种抗肿瘤的新化合物。
本发明的一个目的在于：提供一种具有骨髓瘤抑制作用的吲哚类化合物，该化合物能够有效抑制多发性骨髓瘤细胞U266细胞。
本发明的另一个目的在于：提供所述的吲哚类化合物在药学上可接受的盐。
本发明的再一个目的在于：提供所述吲哚类化合物的制备方法。
本发明的再一个目的在于：提供所述吲哚类化合物的应用。
附图说明
图1化合物浓度为20uM对不同肿瘤细胞的抑制率。
具体实施方式
实施例1化合物的合成如式Ⅰ所示化合物采用如下反应式合成：
在氯仿(20 mL) 溶液中加入5-甲氧基色胺 (3.0 mmol)，逐滴加入三乙胺(6.0mmol)，搅拌5min后，加入3，5-双(三氟甲基)苯基异硫氰酯(3.0 mmol)。搅拌回流8小时，混合液冷却至常温，用布氏漏斗过滤，每次用30ml的乙醇洗涤滤饼三次，收集滤液，并将其悬干，浓缩至干燥得到的固体再次经过经95%乙醇(30 mL)洗涤，过滤后为收集白色固体，得到终产物。
本发明还提供上述化合物或其药学上可接受盐在肿瘤抑制方面的用途。
本发明制备的化合物或其药学上可接受的盐，具有较明显的治疗骨髓瘤但不限于骨髓瘤的效果。
本发明制备的化合物或其药学上可接受的盐，具有较明显的治疗多发性骨髓瘤效果。
本发明还提供本发明所述的化合物的药学上可接受的盐，所述盐可以是磷酸盐，硝酸盐、硫酸盐或盐酸盐等。
实验证明，采用MTT法测试了该化合物对人多发性骨髓瘤U266、人小细胞肺癌SCLC-21H、人***细胞HL-60、淋巴瘤U698的抑制作用，对人多发性骨髓瘤U266的抑制作用比更强，因此发明化合物可用于制备治疗多发性骨髓瘤U266的药物。
本发明还提供上述化合物或其药学上可接受的盐在制备治疗骨髓瘤但不限于骨髓瘤药物中的用途。进一步的，所述化合物可以用于骨髓瘤但不限于骨髓瘤的相关治疗。
下面结合实施例对本发明的具体实施方式做进一步的描述，并不因此将本发明限制在所述的实施列范围之中。
1H-NMR (400 MHz， DMSO-d 6)， δ(ppm): 10.68 (1H， brs)， 10.14 (1H， brs)，8.26 (2H， brs)， 7.72 (1H， brs)， 7.23 (1H， d， J = 8.8 Hz)， 7.16 (1H， d， J =2.1 Hz)， 6.73 (1H， dd， J = 8.8， 2.1 Hz)， 3.80 (2H， m)， 3.75 (3H， s)， 2.98(2H， t， J = 7.2 Hz)。
13C-NMR (100 MHz， DMSO-d 6)，δ(ppm): 180.9， 153.5， 142.4， 131.9， 131.9，130.6 (33.5 Hz)， 130.6 (33.5 Hz)， 128.1， 125.1， 124.0， 122.4， 122.4， 118.1(324.6 Hz)， 118.1 (324.6 Hz)， 112.5， 111.6， 100.9， 55.8， 44.9， 24.8。
Claims (1)
1.结构式如式Ⅰ所示的化合物或其药学上可接受的盐在制备治疗人多发性骨髓瘤药物中的应用
式Ⅰ
。
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| WO2016191911A1 (en) * | 2015-05-29 | 2016-12-08 | Wuhu Eastinno Biotechnologies Co., Ltd. | Pharmaceutical composition and use thereof and methods of treating diseases mediated by hedgehog signaling pathway |
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| CN107820495A (zh) * | 2015-04-29 | 2018-03-20 | 桑福德-伯纳姆医学研究院 | 靶向epha4的配体结合域的新型epha4抑制剂 |
| CN109516926A (zh) * | 2018-07-27 | 2019-03-26 | 四川大学 | 一种荜茇明碱衍生物的制备与抗肿瘤活性 |
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| EP1874952A2 (en) * | 2005-04-11 | 2008-01-09 | Achillion Pharmaceuticals, Inc. | Pharmaceutical compositions for and methods of inhibiting hcv replication |
| JP2011507910A (ja) * | 2007-12-21 | 2011-03-10 | ユニバーシティー オブ ロチェスター | 真核生物の寿命を変更するための方法 |
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| CN107820495A (zh) * | 2015-04-29 | 2018-03-20 | 桑福德-伯纳姆医学研究院 | 靶向epha4的配体结合域的新型epha4抑制剂 |
| WO2016191911A1 (en) * | 2015-05-29 | 2016-12-08 | Wuhu Eastinno Biotechnologies Co., Ltd. | Pharmaceutical composition and use thereof and methods of treating diseases mediated by hedgehog signaling pathway |
| TW201739768A (zh) * | 2016-05-06 | 2017-11-16 | 艾伯維史坦森特瑞斯有限責任公司 | 新穎抗tnfrsf21抗體及使用方法 |
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