CN106496203A - 一种喹啉酮类化合物的制备方法与作为抗单纯疱疹ⅰ型病毒剂的应用 - Google Patents

一种喹啉酮类化合物的制备方法与作为抗单纯疱疹ⅰ型病毒剂的应用 Download PDF

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CN106496203A
CN106496203A CN201510918373.1A CN201510918373A CN106496203A CN 106496203 A CN106496203 A CN 106496203A CN 201510918373 A CN201510918373 A CN 201510918373A CN 106496203 A CN106496203 A CN 106496203A
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邵长伦
王长云
胥汝芳
管菲菲
魏美燕
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Abstract

一种喹啉酮类化合物的制备方法与作为抗单纯疱疹Ⅰ型病毒剂的应用。本发明提供一种抗单纯疱疹Ⅰ型病毒剂，其特征在于以本发明的式I和式II化合物或其药学上可接受的盐，用于治疗单纯疱疹Ⅰ型病毒引起的疾病。

Description

一种喹啉酮类化合物的制备方法与作为抗单纯疱疹Ⅰ型病毒 剂的应用
技术领域
本发明公开了一种喹啉酮类(Quinolinone)化合物在制备抗单纯疱疹Ⅰ型病毒(HSV-1,Herpes Simplex Virus 1)剂中的应用。
背景技术
单纯疱疹Ⅰ型病毒(HSV-1)是一种包裹着的DNA病毒，具有高发病率，潜伏期长，嗜神经组织的特点，潜伏于周围神经系统，主要感染儿童，免疫力低下者以及器官移植者，一旦受到外界适当刺激就会大规模爆发，引发脑炎和角膜炎，严重者能致人死亡。目前临床上抗病毒药物主要是核苷类抗生素，如阿昔洛韦，但近年来耐药性感染人群迅速增加。因此，寻找新的抗病毒药物尤其是结构新颖的抗病毒药物已成为亟待解决的课题。海洋微生物独特的生存环境(高压、高盐、缺氧、避光等)，促使海洋微生物产生大量结构新颖、具有抗病毒活性的化合物，为寻找潜在的抗病毒药物提供了重要来源。但是关于海洋微生物来源的具有抗HSV-1活性的化合物的报道还相当少，尤其是具有潜在开发成为手性药物的海洋来源化合物的报道。（Newman, D. J.; Cragg, G. M. J. Nat. Prod. 2012, 75, 311–335；Blunt, J. W.; Copp, B. R.; Keyzers, R. A.; Munro, M. H. G.; Prinsep, M. R.Nat. Prod. Rep. 2014, 31, 160–258, and previous annual reports.）。
发明内容
本发明提供了一类喹啉酮类化合物，它是一类具有抗HSV-1型病毒的活性化合物。
本发明的目的在于提供了一类喹啉酮生物碱化合物或其药学上可接受的盐用于由单纯疱疹Ⅰ型病毒引起的神经炎症及其它疾病。
本发明提供式I和式II化合物或其药学上可接受的盐:
或其药学上可接受的盐。式I中R为H或
或 或 或 或 或 或 或或或 或 R与苯环上的a、b位碳原子共同形成的或，R1为H或OCH3，R2为H或OH或OCH3，R3为H或OH或OCH3，R4为H或OH。
R1为H或OCH3，R2为H或OH，R3为OH或OCH3，R4为H或CH3。
本发明中式I化合物其特征在于选自如下化合物：
本发明中式II化合物其特征在于选自如下化合物：
化合物1-4已公开于文献[1]Chang-Lun Shao, Ru-Fang Xu, Chang-Yun Wang, Pei-Yuan Qian, Kai-Ling Wang, Mei-Yan Wei, Potent Antifouling MarineDihydroquinolin-2(1H)-one-Containing Alkaloids from the Gorgonian Coral-Derived Fungus Scopulariopsissp. Mar Biotechnol. 2015, 17:408-415; [2] MinChen, Chang-Lun Shao, Hong Meng, Zhi-Gang She, Chang-Yun Wang, Anti-Respiratory Syncytial Virus Prenylated Dihydroquinolone Derivatives from theGorgonian-Derived Fungus Aspergillus sp. XS-20090B15. J. Nat. Prod. 2014, 77:2720−2724；[3] Scott A. Ne, Sang Un Lee, Yukihiro Asami, Jong Seog Ahn,Hyuncheol Oh, Jonas Baltrusaitis, James B. Gloer, Donald T. Wicklow,Aflaquinolones A−G: Secondary Metabolites from Marine and FungicolousIsolates of Aspergillus spp. J. Nat. Prod. 2012, 75, 464−472。化合物5-8已公开于文献Kirstin Scherlach, Christian Hertweck, Discovery of aspoquinolones A–D,prenylated quinoline-2-one alkaloids from Aspergillus nidulans, motivated bygenome mining, Org. Biomol. Chem. 2006,4:3517-3520。化合物9,10，18-21已公开于文献[1] Ryuji Uchida, Rie Imasato, Hiroshi Tomoda, Satoshi Ōmura，Yaequinolones, New Insecticidal Antibiotics Produced by Penicillium sp. FKI-2140’, J. Antibiot. 2006, 59(10): 646-658; [2] Ryuji Uchida, Rie Imasato,Kazuro Shiomi, Hiroshi Tomoda, Satoshi Ohmura, Yaequinolones J1 and J2, NovelInsecticidal Antibiotics from Penicillium sp. FKI-2140. Org. Lett. 2005, 7(25): 5701-5704。化合物11,12以已公开于文献[1]Yasuo Kimura, Miyako Kusano,Hiroyuki Koshino, Jun Uzawa, Shozo Fujioka，Kiyotsugu Tani, Penigequinolones Aand B, Pollen-growth Inhibitors Produced by Penicillium sp., No. 410.Tetrahedron Letters. 1996, 37(28):4961-4964;[2] Thomas O. Larsen, JørnSmedsgaard, Jens C. Frisvad, Uffe Anthoni, Carsten Christophersen, Consistentproduction of penigequinolone A and B by Penicillium scabrosum. BiochemicalSystematics and Ecology. 1999, 27 :329-332。 化合物13,14已公开于文献Li-YingMa, Wei-Zhong Liu, Li Shen, Yu-Ling Huang, Xian-Guo Rong,Yan-Yan Xu, Xue-DongGao，Spiroketals, isocoumarin and indoleformic acid derivatives from salinesoil derived fungus Penicillium raistrickii. Tetrahedron. 2012, 68: 2276-2282。化合物15,16已公开于文献Hideo Hayashi, Tadashi Nakatani, Yoshiki Inoue,Mitsuru Nakayama, Hiroshi Nozaki, New Dihydroquinolinone Toxic to Artemiasalina Produced by Penicilliumsp. NTC-47. Biosci. Biotech. Biochem. 1997, 61(5):914-916。化合物17已公开于文献Miyako Kusano, Hiroyuki Koshino, Jun Uzawa,Shozo Fujioka, Tsuyoshi Kawano, Yasuo Kimura, Nematicidal Alkaloids andRelated Compounds Produced by the Fugus Penicillium cf. simplicissimum.Biosci. Biotech. Biochem. 2000, 64(12):2559-2568。化合物22-28已公开于文献YiZhang, Jun Mu, Frank Essmannh, Yan Feng, Markus Kramer, Hai-yan Bao,Stephanie Grond, A new quinolinone and its natural/artificial derivativesfrom a shark gill-derived fungus Penicillium crustosum AP2T1. Natural ProductResearch. 2015。化合物29已公开于文献 Cunningham K. G.，Freeman G. G.，Isolationand some chemical properties of viridicatin, a metabolic product ofPenicillium viridicatum. Biochemical Journal. 1953, 53, 328-332。化合物30已公开于文献 Alex Ciegler, Ching T. Hou, Isolation of Viridicatin fromPenicillium palitans. Arch. Mikrobiol. 1970, 73: 261-267。
本发明化合物包括所有立体异构体，无论是混合物形式或是纯异构体的形式，式I及式II化合物可以以对映体或非对映体形式或其混合物的形式存在。
本发明中术语“药学上可接受的盐”是指非毒性的无机或有机酸和/或碱的加成盐。可参见“Salt selection for basic drugs”, Int. J. Pharm. (1986), 33, 201–217。
发明中式I和式II所示的喹啉酮类化合物均是从真菌中分离获得的，属于天然活性成分，对单纯疱疹Ⅰ型病毒具有极强的抑制活性，可单独或组合成药，用于开发为抗单纯疱疹Ⅰ型病毒剂，应用前景广阔。
本发明的另一实施方案提供式I和式II化合物或其药学上可接受的盐在制备抗单纯疱疹Ⅰ型病毒剂中的应用。
具体实施方式
为了便于对本发明的进一步理解，下面提供的实施例对其做了更详细的说明。但是这些实施例仅供更好的理解发明而并非用来限定本发明的范围或实施原则，本发明的实施方式不限于以下内容。
实施例
式Ⅰ化合物的抗病毒活性
(1) 抗病毒活性测试
采用细胞病变抑制作用（CPE）对单纯疱疹Ⅰ型病毒(HSV-1)的体外抗病毒活性进行测试。
(2) 活性测试方法
将培养成单层的Hep-2细胞用胰酶消化后，接种于96孔板中，长成单层备用。将HSV-1病毒接种于Hep-2细胞上，加2%血清1640培养液后置37℃、5%CO2条件下培养，出现90%以上的病变后，反复冻融3次后吹打离心，定量分装，–80℃冰箱冻存备用。受试样品每管以10μLDMSO溶解后，加入200μL的2% 1640培养液，并连续10次2倍比稀释，共10个稀释度，然后横向接种于96板孔中的单层细胞上，11列为病毒对照、12列为细胞对照，37℃、5% CO2培养，每小时观察病变，连续观察24h（HSV-1）。病毒对照出现90%以上的病变后，将板孔内液体吸弃，加1%中性红染色，在540 nm波长测定OD值，用Reed-Muench方法计算药物半数有效浓度(IC50)，观察药物抑杀病毒的效果。
(3) 活性测试结果
试验结果显示，本发明制备的式I和式II化合物对HSV-1感染具有不同程度的抑制作用，IC50值均在 0.1-100 μM之间，活性尤为突出的是化合物1,2和4，其抗HSV-1病毒IC50值分别为0.16 μM ，0.20 μM 和0.80 μM，远远强于阳性药利巴韦林（IC50 = 78 μM）的活性。
实验表明，本发明的喹啉酮类化合物对HSV-1感染具有很强的抑制活性，可将其制成抗病毒药物，由于该类化合物来源于微生物，可进行大规模发酵生产，保证了式I和式II化合物的天然来源，具有广阔的应用前景。

Claims (7)

1.一种具有式I和式II结构的喹啉酮类化合物或其药学上可接受的盐在制备抗单纯疱疹Ⅰ型病毒剂中的应用，其特征在于：
式I具有以下结构，其中R为H或或 或 或或 或 或 或 或或 或 R与苯环上的a、b位碳原子共同形成的或，R1为H或OCH3，R2为H或OH或OCH3，R3为H或OH或OCH3，R4为H或OH;
式II具有以下结构 ，其中R1为H或OCH3，R2为H或OH，R3为OH或OCH3，R4为H或CH3。
2.权利要求1所述的应用，其特征在于式I化合物选自如下化合物：
。
3.权利要求1所述的应用，其特征在于式II化合物选自如下化合物：
。
4.一种抗单纯疱疹Ⅰ型病毒剂，其特征在于其含有权利要求1-3任一项所述的式I及式II化合物或其药学上可接受的盐作为有效成分。
5.一种药物组合物，其特征在于其含有权利要求1-3所述的任一项化合物或其药学上可接受的盐以及药学上可接受的载体、稀释剂、赋形剂。
6.权利要求5所述的药物组合物，其特征在于其还包括其他治疗剂。
7.权利要求6所述的药物组合物，其特征在于所述的其他治疗剂为抗病毒剂。
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108658974A (zh) * 2017-03-28 2018-10-16 中国海洋大学 一种内酰胺类化合物及其制备方法和用途
CN110041283A (zh) * 2018-01-15 2019-07-23 中国医学科学院药物研究所 板蓝根中具有抗多种病毒活性的含硫类化合物及其用途

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108658855A (zh) * 2017-03-28 2018-10-16 中国海洋大学 一种含氮双环化合物及其制备方法和用途
CN108658972A (zh) * 2017-03-28 2018-10-16 中国海洋大学 一种取代内酰胺类化合物及其制备方法和用途

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103554090A (zh) * 2013-10-15 2014-02-05 中国海洋大学 一种萜类二氢喹啉酮生物碱化合物及其晶体、制备方法与作为海洋防污剂的应用

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120040033A1 (en) * 2010-08-10 2012-02-16 Ernest Timothy Armstrong Anti-infective mangrove extract against viruses, bacteria and fungi

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103554090A (zh) * 2013-10-15 2014-02-05 中国海洋大学 一种萜类二氢喹啉酮生物碱化合物及其晶体、制备方法与作为海洋防污剂的应用

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
KIRSTIN SCHERLACH ET AL.: "Discovery of aspoquinolones A-D, prenylated quinoline-2-one alkaloids from Aspergillus nidulans, motivated by genome mining", 《ORG. BIOMOL. CHEM.》 *
MIN CHEN ET AL.: "Anti-Respiratory Syncytial Virus Prenylated Dihydroquinolone Derivatives from the Gorgonian-Derived Fungus Aspergillus sp. XS-20090B15", 《J. NAT. PROD.》 *
MIYAKO KUSANO ET AL.: "Nematicidal Alkaloids and Related Compounds Produced by the Fungus Penicillium cf. simplicissimum", 《BIOSCI. BIOTECHNOL. BIOCHEM.》 *
RYUJI UCHIDA ET AL.: "Yaequinolones, New Insecticidal Antibiotics Produced by Penicillium sp. FKI-2140", 《J. ANTIBIOT.》 *
SCOTT A. NEFF ET AL.: "Aflaquinolones A-G: Secondary Metabolites from Marine and Fungicolous Isolates of Aspergillus spp.", 《J. NAT. PROD.》 *
YI ZHANG ET AL.: "A new quinolinone and its natural/artificial derivatives from a shark gill-derived fungus penicillium crustosum AP2T1", 《NATURAL PRODUCT RESEARCH》 *
胥汝芳: "柳珊瑚来源的一株真菌中生物碱化合物及其生物活性", 《中国优秀硕士学位论文全文数据库（电子期刊）》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108658974A (zh) * 2017-03-28 2018-10-16 中国海洋大学 一种内酰胺类化合物及其制备方法和用途
CN110041283A (zh) * 2018-01-15 2019-07-23 中国医学科学院药物研究所 板蓝根中具有抗多种病毒活性的含硫类化合物及其用途
CN110041283B (zh) * 2018-01-15 2022-05-17 中国医学科学院药物研究所 板蓝根中具有抗多种病毒活性的含硫类化合物及其用途

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