CN115487189B - 一种穿心莲內酯衍生物的应用 - Google Patents
一种穿心莲內酯衍生物的应用 Download PDFInfo
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- CN115487189B CN115487189B CN202211316396.1A CN202211316396A CN115487189B CN 115487189 B CN115487189 B CN 115487189B CN 202211316396 A CN202211316396 A CN 202211316396A CN 115487189 B CN115487189 B CN 115487189B
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- BOJKULTULYSRAS-OTESTREVSA-N Andrographolide Chemical class C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CCC1=C)(CO)C)\C=C1/[C@H](O)COC1=O BOJKULTULYSRAS-OTESTREVSA-N 0.000 title claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 12
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- 125000000217 alkyl group Chemical group 0.000 description 6
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- OLJNUUXYMNOVFR-NSOVKSMOSA-N (2s)-2-amino-n-[2-[[4-[[2-[[(2s)-2-amino-3-(1h-indol-3-yl)propanoyl]amino]acetyl]amino]-9,10-dioxoanthracen-1-yl]amino]-2-oxoethyl]-3-(1h-indol-3-yl)propanamide Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1C(NC(=O)CNC(=O)[C@@H](N)CC=1C3=CC=CC=C3NC=1)=CC=C2NC(=O)CNC(=O)[C@@H](N)CC1=CNC2=CC=CC=C12 OLJNUUXYMNOVFR-NSOVKSMOSA-N 0.000 description 1
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- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
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- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 description 1
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- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
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- 125000000168 pyrrolyl group Chemical group 0.000 description 1
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- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 1
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- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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Abstract
本发明公开了一种穿心莲內酯衍生物的应用，本发明穿心莲內酯衍生物、其异构体或其盐能够制备用于老年痴呆症的药物，用于抗肿瘤的药物，用于治疗或预防疾病药物中的应用，所述肿瘤包括结肠癌、卵巢癌、乳腺癌，具有良好的临床应用前景。
Description
技术领域
本发明属于药物化学技术领域，具体涉及一种穿心莲內酯衍生物的应用。
背景技术
阿尔茨海默病(Alzheimer’s症，简称AD)是一种起病隐匿的进行性发展的神经系统退行性疾病，临床上以记忆障碍、失语、失用、失认、视空间技能损害、执行功能障碍以及人格和行为改变等全面性痴呆表现为特征。研究表明AD患者的大脑内部发生了一系列变化，其中脑部主要的宏观变化是大脑皮质的普遍萎缩，神经细胞常出现神经原纤维缠结呈双股螺旋状丝，淀粉样蛋白在细胞外沉积而形成的老年斑常出现在海马回和额叶皮质以及基底节、丘脑、小脑也有发现，但准确的病因迄今未明。
穿心莲内酯衍生物的抗肿瘤活性一直受到关注，但没有取得突破性进展。
发明内容
本部分的目的在于概述本发明的实施例的一些方面以及简要介绍一些较佳实施例。在本部分以及本申请的说明书摘要和发明名称中可能会做些简化或省略以避免使本部分、说明书摘要和发明名称的目的模糊，而这种简化或省略不能用于限制本发明的范围。
本发明提供一种穿心莲內酯衍生物的应用，所述穿心莲內酯衍生物用于制备治疗老年痴呆症和抗肿瘤的药物，所述穿心莲內酯衍生物，包括下式所示的化合物、其异构体或其药学上可接受的盐中的一种或几种，
其中，
Ar是任意取代的苯环、吡啶环、哒嗪环、嘧啶环、吡嗪环、呋喃环、噻唑环、吡咯环、噁唑环、噻唑环、咪唑环、异恶唑环、异噻唑环或吡唑环；
Z为O，或者Z-R6与R7形成羰基、肟、腙；
R7为H，或者与Z-R6形成羰基、肟、腙；
R1～R5分别独立地选自氢、卤素、氰基、硝基、C1～6烷基、C1～6卤代烷基、C1～6酰基、C1～6羧酸基、C1～6酰胺基、取代或非取代的C3～6环烷基、取代或非取代的C1～6烷氧基、取代或非取代的C1～6烷硫基、取代或非取代的C2～6羧酸酯、取代或非取代的氨基、取代或非取代的磺酰基、取代或非取代的C2～6烯烃基、取代或非取代的C3～6环烯烃基、取代或非取代的C3～6杂环基、取代或非取代的芳香基、取代或非取代的芳香烷基；所述取代基选自卤素、氰基、硝基、C1～6烷基、C1～6卤代烷基、C1～6烷氧基、C1～6烷硫基或C2～6烯烃基；
或者R1～R5中相邻的两个基团与Ar环共同构成萘、蒽、菲、喹啉、异喹啉、苯并吡喃、苯并吡喃酮、苯并呋喃、苯并噻吩、吲哚、嘌呤或喋啶基团；
R6或R8分别独立地选自氢、C1～6酰基、取代或非取代的C1～6烷基、取代或非取代的C3～6环烷基、取代或非取代的杂环基、取代或非取代的C2～6烯烃基、取代或非取代的C3～6环烯烃基、取代或非取代的芳香基、取代或非取代的芳香烷基或取代或非取代杂环烯基；；所述取代基选自卤素、氰基、硝基、C1～6烷基、C1～6卤代烷基、C1～6烷氧基、C1～6烷硫基或C2～6烯烃基；
或者R6和R8相连构成C1～6亚烷基或C3～6环烷基；
未取代或任意取代芳香烃基、未取代或任意取代杂环芳香烃基、未取代或任意取代芳香烷基、未取代或任意取代杂环芳香烷基、未取代或任意取代芳香烯烃基、未取代或任意取代杂环芳香烯基
*表示为R构型或S构型。
作为本发明所述穿心莲內酯衍生物的应用的一种优选方案，所述穿心莲內酯衍生物为下式所示化合物、其异构体或其药学上可接受的盐中的一种用于制备治疗老年痴呆症的药物，
本发明还提供一种穿心莲內酯衍生物的应用，所述穿心莲內酯衍生物用于制备治疗老年痴呆症和抗肿瘤的药物，所述穿心莲內酯衍生物，包括下式所示的化合物、其异构体或其药学上可接受的盐中的一种或几种，
本发明的有益效果：本发明发现了穿心莲內酯衍生物、其异构体或其盐能够制备用于老年痴呆症的药物，用于抗肿瘤的药物，用于治疗或预防疾病药物中的应用，其中所述疾病为胆固醇或血脂代谢异常、糖尿病、肥胖症、心血管病变、免疫性疾病、炎症、Parkinson症或神经障碍类疾病。
附图说明
为了更清楚地说明本发明实施例的技术方案，下面将对实施例描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动性的前提下，还可以根据这些附图获得其它的附图。其中：
图1为本发明AGF系列化合物在SH-SY5Y细胞(人神经母细胞瘤细胞)中对sAPPα分泌激活，βAPP蛋白量及其sAPPα/βAPP比例的影响(图中数字7-18与化合物编号对应关系：7＝AGF-1，8＝AGF-2，9＝AGF-12，10＝AGF-6，11＝AGF-11，12＝AGF-3，13＝AGF-15，14＝AGF-4，15＝AGF-14，16＝AGF-8，17＝AGF-16，18＝AGF-5；CT：对照；andro：穿心莲内酯)。
图2为各化合物抗肿瘤活性，AGW-11、AGW-12、ZWK-17均表现出较好的抗肿瘤活性(图中箭头指示化合物的对应抑制曲线)，其中MDA-MB-231(人源)和4T1(鼠源)为三阴乳腺癌细胞系。
具体实施方式
表1本发明化合物的抗肿瘤活性
表2本发明化合物的抗肿瘤活性
表3本发明化合物的抗肿瘤活性
Scoreboard:0～10％inhibition rate:O；10％～20％:+；20％～40％:++；40％～60％:+++；60％～80％:++++；80％～100％:+++++；
表4本发明化合物的抗肿瘤活性
Scoreboard:0～10％inhibition rate:O；10％～20％:+；20％～40％:++；40％～60％:+++；60％～80％:++++；80％～100％:+++++；
表5本发明化合物对应的1H NMR数据
本发明提供多个结构位置修饰的穿心莲内酯衍生物的新应用，特别是用于制备抗老年痴呆症的药物、抗肿瘤及其血管新生作用的药物，也可能用来治疗和预防糖尿病和肥胖症及其它代谢性疾病、心血管病变、生殖系统疾病，免疫性疾病、炎症、Parkinson症及其它神经障碍类疾病。具有较好的临床应用前景。
应说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的精神和范围，其均应涵盖在本发明的权利要求范围当中。
Claims (1)
1.一种穿心莲内酯衍生物的应用，其特征在于：所述穿心莲内酯衍生物用于制备治疗结肠癌和/或卵巢癌的药物，所述穿心莲内酯衍生物包括下式所示的化合物或其药学上可接受的盐中的一种或几种，
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| CN103224492A (zh) * | 2013-04-15 | 2013-07-31 | 南京工业大学 | 14-芳基醚穿心莲內酯衍生物及其制备方法和应用 |
| CN104856987A (zh) * | 2015-01-22 | 2015-08-26 | 南京工业大学 | 14-芳基醚穿心莲內酯衍生物在抗菌领域的应用 |
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| CN103224492A (zh) * | 2013-04-15 | 2013-07-31 | 南京工业大学 | 14-芳基醚穿心莲內酯衍生物及其制备方法和应用 |
| CN104856987A (zh) * | 2015-01-22 | 2015-08-26 | 南京工业大学 | 14-芳基醚穿心莲內酯衍生物在抗菌领域的应用 |
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