• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

取代的二（吡啶-2-基）-1,2,4-噻二唑-5-胺类作为新型杀丝虫化合物用于治疗人类丝虫感染的发现。

Discovery of Substituted Di(pyridin-2-yl)-1,2,4-thiadiazol-5-amines as Novel Macrofilaricidal Compounds for the Treatment of Human Filarial Infections.

机构信息

Bristol Myers Squibb, San Diego, California 92121, United States.

Zoetis, Kalamazoo, Michigan 49001, United States.

出版信息

J Med Chem. 2022 Aug 25;65(16):11388-11403. doi: 10.1021/acs.jmedchem.2c00960. Epub 2022 Aug 16.

DOI:10.1021/acs.jmedchem.2c00960
PMID:35972896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9421654/
Abstract

Filarial diseases, including lymphatic filariasis and onchocerciasis, are considered among the most devastating of all tropical diseases, affecting about 145 million people worldwide. Efforts to control and eliminate onchocerciasis are impeded by a lack of effective treatments that target the adult filarial stage. Herein, we describe the discovery of a series of substituted di(pyridin-2-yl)-1,2,4-thiadiazol-5-amines as novel macrofilaricides for the treatment of human filarial infections.

摘要

丝虫病，包括淋巴丝虫病和盘尾丝虫病，被认为是所有热带病中最具破坏性的疾病之一，影响全球约 1.45 亿人。由于缺乏针对成虫阶段的有效治疗方法，控制和消除盘尾丝虫病的工作受到阻碍。在此，我们描述了一系列取代的二（吡啶-2-基）-1,2,4-噻二唑-5-胺作为新型的大环丝虫药物的发现，用于治疗人类丝虫感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28fc/9421654/0ea8589966e0/jm2c00960_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28fc/9421654/6ca35e1aacdd/jm2c00960_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28fc/9421654/366f131e4b9e/jm2c00960_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28fc/9421654/754f799b53b7/jm2c00960_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28fc/9421654/0ea8589966e0/jm2c00960_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28fc/9421654/6ca35e1aacdd/jm2c00960_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28fc/9421654/366f131e4b9e/jm2c00960_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28fc/9421654/754f799b53b7/jm2c00960_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28fc/9421654/0ea8589966e0/jm2c00960_0003.jpg

相似文献

1
Discovery of Substituted Di(pyridin-2-yl)-1,2,4-thiadiazol-5-amines as Novel Macrofilaricidal Compounds for the Treatment of Human Filarial Infections.取代的二（吡啶-2-基）-1,2,4-噻二唑-5-胺类作为新型杀丝虫化合物用于治疗人类丝虫感染的发现。
J Med Chem. 2022 Aug 25;65(16):11388-11403. doi: 10.1021/acs.jmedchem.2c00960. Epub 2022 Aug 16.
2
Anti-Wolbachia drugs for filariasis.用于治疗丝虫病的抗沃尔巴克氏体药物。
Trends Parasitol. 2021 Dec;37(12):1068-1081. doi: 10.1016/j.pt.2021.06.004. Epub 2021 Jul 3.
3
Anti- therapy for onchocerciasis & lymphatic filariasis: Current perspectives.抗丝虫病和淋巴丝虫病治疗：当前观点。
Indian J Med Res. 2019 Jun;149(6):706-714. doi: 10.4103/ijmr.IJMR_454_17.
4
Filarial nematode phenotypic screening cascade to identify compounds with anti-parasitic activity for drug discovery optimization.丝状线虫表型筛选级联反应，用于鉴定具有抗寄生虫活性的化合物，以优化药物发现。
Int J Parasitol Drugs Drug Resist. 2022 Aug;19:89-97. doi: 10.1016/j.ijpddr.2022.06.002. Epub 2022 Jun 23.
5
Eosinophils in filarial infections: Inducers of protection or pathology?丝虫感染中的嗜酸性粒细胞：保护诱导剂还是病理诱导剂？
Front Immunol. 2022 Oct 31;13:983812. doi: 10.3389/fimmu.2022.983812. eCollection 2022.
6
Lymphatic filariasis and onchocerciasis.淋巴丝虫病和盘尾丝虫病。
Lancet. 2010 Oct 2;376(9747):1175-85. doi: 10.1016/S0140-6736(10)60586-7. Epub 2010 Aug 23.
7
Recent advances in the chemotherapy of lymphatic filariasis.淋巴丝虫病化疗的最新进展。
Southeast Asian J Trop Med Public Health. 1993;24 Suppl 2:51-4.
8
Development and validation of a high-throughput anti-Wolbachia whole-cell screen: a route to macrofilaricidal drugs against onchocerciasis and lymphatic filariasis.高通量抗沃尔巴克氏体全细胞筛选方法的开发与验证：一条通往抗盘尾丝虫病和淋巴丝虫病的杀成虫药物的途径
J Biomol Screen. 2015 Jan;20(1):64-9. doi: 10.1177/1087057114551518. Epub 2014 Oct 2.
9
Identifying co-endemic areas for major filarial infections in sub-Saharan Africa: seeking synergies and preventing severe adverse events during mass drug administration campaigns.确定撒哈拉以南非洲地区主要丝虫病的共同流行地区：在大规模药物治疗运动中寻求协同作用并预防严重不良事件。
Parasit Vectors. 2018 Jan 31;11(1):70. doi: 10.1186/s13071-018-2655-5.
10
A murine macrofilaricide pre-clinical screening model for onchocerciasis and lymphatic filariasis.一种用于盘尾丝虫病和淋巴丝虫病的小鼠大型丝虫杀虫剂临床前筛选模型。
Parasit Vectors. 2014 Oct 24;7:472. doi: 10.1186/s13071-014-0472-z.

引用本文的文献

1
Filariasis research - from basic research to drug development and novel diagnostics, over a decade of research at the Institute for Medical Microbiology, Immunology and Parasitology, Bonn, Germany.丝虫病研究——从基础研究到药物研发与新型诊断，德国波恩医学微生物学、免疫学与寄生虫学研究所十年研究历程
Front Trop Dis. 2023 Mar 2;4. doi: 10.3389/fitd.2023.1126173.

本文引用的文献

1
Filarial nematode phenotypic screening cascade to identify compounds with anti-parasitic activity for drug discovery optimization.丝状线虫表型筛选级联反应，用于鉴定具有抗寄生虫活性的化合物，以优化药物发现。
Int J Parasitol Drugs Drug Resist. 2022 Aug;19:89-97. doi: 10.1016/j.ijpddr.2022.06.002. Epub 2022 Jun 23.
2
Optimization of dose and route of administration of the P-glycoprotein inhibitor, valspodar (PSC-833) and the P-glycoprotein and breast cancer resistance protein dual-inhibitor, elacridar (GF120918) as dual infusion in rats.优化 P-糖蛋白抑制剂瓦他拉尼（PSC-833）和 P-糖蛋白及乳腺癌耐药蛋白双重抑制剂依利格鲁司他（GF120918）的剂量和给药途径，作为双重输注在大鼠中的应用。
Pharmacol Res Perspect. 2021 Apr;9(2):e00740. doi: 10.1002/prp2.740.
3
Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections.短程抗沃尔巴克氏体、杀微丝蚴治疗丝虫感染的珊瑚嘌呤 A。
PLoS Negl Trop Dis. 2020 Dec 7;14(12):e0008930. doi: 10.1371/journal.pntd.0008930. eCollection 2020 Dec.
4
Oxfendazole mediates macrofilaricidal efficacy against the filarial nematode Litomosoides sigmodontis in vivo and inhibits Onchocerca spec. motility in vitro.奥芬达唑对体内丝状线虫秀丽隐杆线虫具有杀微丝蚴作用，并抑制体外盘尾丝虫属运动。
PLoS Negl Trop Dis. 2020 Jul 6;14(7):e0008427. doi: 10.1371/journal.pntd.0008427. eCollection 2020 Jul.
5
Macrofilaricides: An Unmet Medical Need for Filarial Diseases.杀微丝蚴剂：丝虫病未满足的医学需求。
ACS Infect Dis. 2020 Apr 10;6(4):662-671. doi: 10.1021/acsinfecdis.9b00469. Epub 2020 Mar 5.
6
In vivo efficacy of the boron-pleuromutilin AN11251 against Wolbachia of the rodent filarial nematode Litomosoides sigmodontis.体内硼-截短侧耳素 AN11251 抗鼠丝虫利什曼原虫沃尔巴克氏体的疗效。
PLoS Negl Trop Dis. 2020 Jan 27;14(1):e0007957. doi: 10.1371/journal.pntd.0007957. eCollection 2020 Jan.
7
In vivo kinetics of Wolbachia depletion by ABBV-4083 in L. sigmodontis adult worms and microfilariae.在感染利什曼原虫的西格氏硕大利什曼原虫成虫和微丝蚴中，用 ABBV-4083 耗竭沃尔巴克氏体的体内动力学研究。
PLoS Negl Trop Dis. 2019 Aug 5;13(8):e0007636. doi: 10.1371/journal.pntd.0007636. eCollection 2019 Aug.
8
Discovery of short-course antiwolbachial quinazolines for elimination of filarial worm infections.发现短程抗沃尔巴克氏体喹唑啉类药物消除丝虫感染。
Sci Transl Med. 2019 May 8;11(491). doi: 10.1126/scitranslmed.aav3523.
9
Discovery of ABBV-4083, a novel analog of Tylosin A that has potent anti-Wolbachia and anti-filarial activity.发现 ABBV-4083，一种泰乐菌素 A 的新型类似物，具有强大的抗沃尔巴克氏体和抗丝虫活性。
PLoS Negl Trop Dis. 2019 Feb 28;13(2):e0007159. doi: 10.1371/journal.pntd.0007159. eCollection 2019 Feb.
10
Boron-Pleuromutilins as Anti- Wolbachia Agents with Potential for Treatment of Onchocerciasis and Lymphatic Filariasis.硼-磷霉素类化合物作为抗沃尔巴克氏体药物，有望用于治疗盘尾丝虫病和淋巴丝虫病。
J Med Chem. 2019 Mar 14;62(5):2521-2540. doi: 10.1021/acs.jmedchem.8b01854. Epub 2019 Feb 26.