小分子抗疟药的案例研究：2-氨基-1-苯乙醇（APE）衍生物
Case Study of Small Molecules As Antimalarials: 2-Amino-1-phenylethanol (APE) Derivatives.
作者信息
Chaparro María J, Vidal Jaume, Angulo-Barturen Iñigo, Bueno José M, Burrows Jeremy, Cammack Nicholas, Castañeda Pablo, Colmenarejo Gonzalo, Coterón José M, de Las Heras Laura, Fernández Esther, Ferrer Santiago, Gabarró Raquel, Gamo Francisco J, García Mercedes, Jiménez-Díaz María B, Lafuente María J, León María L, Martínez María S, Minick Douglas, Prats Sara, Puente Margarita, Rueda Lourdes, Sandoval Elena, Santos-Villarejo Angel, Witty Michael, Calderón Félix
机构信息
Tres Cantos, Medicines Development Campus, DDW, GlaxoSmithKline , Severo Ochoa 2, 28760 Tres Cantos, Madrid, Spain.
Medicines for Malaria Venture (MMV) , 20 route de Pré-Bois, 1215 Geneva 15, Switzerland.
出版信息
ACS Med Chem Lett. 2014 Mar 26;5(6):657-61. doi: 10.1021/ml500015r. eCollection 2014 Jun 12.
Abstract
Antiparasitic oral drugs have been associated to lipophilic molecules due to their intrinsic permeability. However, these kind of molecules are associated to numerous adverse effects, which have been extensively studied. Within the Tres Cantos Antimalarial Set (TCAMS) we have identified two small, soluble and simple hits that even presenting antiplasmodial activities in the range of 0.4-0.5 μM are able to show in vivo activity.
摘要
由于其固有的渗透性，抗寄生虫口服药物与亲脂性分子有关。然而，这类分子与众多不良反应相关，这些不良反应已得到广泛研究。在特雷斯坎托斯抗疟药物组合（TCAMS）中，我们鉴定出了两种小的、可溶且结构简单的活性化合物，它们即使在0.4 - 0.5 μM范围内呈现抗疟原虫活性，也能够表现出体内活性。
相似文献
1
Case Study of Small Molecules As Antimalarials: 2-Amino-1-phenylethanol (APE) Derivatives.小分子抗疟药的案例研究：2-氨基-1-苯乙醇（APE）衍生物
ACS Med Chem Lett. 2014 Mar 26;5(6):657-61. doi: 10.1021/ml500015r. eCollection 2014 Jun 12.
2
Cyclopropyl Carboxamides: A New Oral Antimalarial Series Derived from the Tres Cantos Anti-Malarial Set (TCAMS).环丙基甲酰胺：源自特雷斯坎托斯抗疟药库（TCAMS）的新型口服抗疟药系列。
ACS Med Chem Lett. 2011 Aug 29;2(11):840-4. doi: 10.1021/ml2001517. eCollection 2011 Nov 10.
3
Collaborative drug discovery and the Tres Cantos Antimalarial Set (TCAMS).合作药物发现和特雷斯坎托抗疟集（TCAMS）。
Drug Discov Today. 2019 Jun;24(6):1304-1310. doi: 10.1016/j.drudis.2019.04.005. Epub 2019 Apr 10.
4
Novel 2-Phenoxyanilide Congeners Derived from a Hit Structure of the TCAMS: Synthesis and Evaluation of Their in Vitro Activity against Plasmodium falciparum.源自三嗪类抗疟化合物筛选命中结构的新型2-苯氧基苯胺类似物：其对恶性疟原虫体外活性的合成与评价
Molecules. 2016 Feb 17;21(2):223. doi: 10.3390/molecules21020223.
5
Hundreds of dual-stage antimalarial molecules discovered by a functional gametocyte screen.通过功能配子体筛选发现了数百种双阶段抗疟分子。
Nat Commun. 2017 May 17;8:15160. doi: 10.1038/ncomms15160.
6
High-Content Phenotypic Screen of a Focused TCAMS Drug Library Identifies Novel Disruptors of the Malaria Parasite Calcium Dynamics.聚焦型TCAMS药物文库的高内涵表型筛选鉴定出疟原虫钙动力学的新型干扰剂。
ACS Chem Biol. 2021 Nov 19;16(11):2348-2372. doi: 10.1021/acschembio.1c00512. Epub 2021 Oct 5.
7
Investigating the antiplasmodial activity of primary sulfonamide compounds identified in open source malaria data.研究在开源疟疾数据中鉴定出的伯胺类化合物的抗疟活性。
Int J Parasitol Drugs Drug Resist. 2017 Apr;7(1):61-70. doi: 10.1016/j.ijpddr.2017.01.003. Epub 2017 Jan 13.
8
A New Set of Chemical Starting Points with Plasmodium falciparum Transmission-Blocking Potential for Antimalarial Drug Discovery.一组具有阻断恶性疟原虫传播潜力的新化学起始点，用于抗疟药物发现。
PLoS One. 2015 Aug 28;10(8):e0135139. doi: 10.1371/journal.pone.0135139. eCollection 2015.
9
Carbamoyl Triazoles, Known Serine Protease Inhibitors, Are a Potent New Class of Antimalarials.氨基甲酰三唑类化合物，即已知的丝氨酸蛋白酶抑制剂，是一类新型强效抗疟药物。
J Med Chem. 2015 Aug 27;58(16):6448-55. doi: 10.1021/acs.jmedchem.5b00434. Epub 2015 Aug 17.
10
A Divergent SAR Study Allows Optimization of a Potent 5-HT2c Inhibitor to a Promising Antimalarial Scaffold.一项发散性的构效关系研究使得一种强效5-HT2c抑制剂优化为一种有前景的抗疟骨架。
ACS Med Chem Lett. 2012 Feb 9;3(5):373-7. doi: 10.1021/ml300008j. eCollection 2012 May 10.
引用本文的文献
1
Structure-activity and structure-property relationship studies of spirocyclic chromanes with antimalarial activity.具有抗疟活性的螺环色满结构-活性和结构-性质关系研究。
Bioorg Med Chem. 2022 Mar 1;57:116629. doi: 10.1016/j.bmc.2022.116629. Epub 2022 Jan 14.
2
Novel 2-Phenoxyanilide Congeners Derived from a Hit Structure of the TCAMS: Synthesis and Evaluation of Their in Vitro Activity against Plasmodium falciparum.源自三嗪类抗疟化合物筛选命中结构的新型2-苯氧基苯胺类似物：其对恶性疟原虫体外活性的合成与评价
Molecules. 2016 Feb 17;21(2):223. doi: 10.3390/molecules21020223.
3
A small-fish model for behavioral-toxicological screening of new antimalarial drugs: a comparison between erythro- and threo-mefloquine.一种用于新型抗疟药物行为毒理学筛选的小鱼模型：赤藓型和苏阿糖型甲氟喹的比较
BMC Res Notes. 2015 Apr 2;8:122. doi: 10.1186/s13104-015-1088-x.
4
Identification and characterization of hundreds of potent and selective inhibitors of Trypanosoma brucei growth from a kinase-targeted library screening campaign.通过激酶靶向文库筛选活动鉴定和表征数百种布氏锥虫生长的强效和选择性抑制剂。
PLoS Negl Trop Dis. 2014 Oct 23;8(10):e3253. doi: 10.1371/journal.pntd.0003253. eCollection 2014 Oct.
本文引用的文献
1
A Divergent SAR Study Allows Optimization of a Potent 5-HT2c Inhibitor to a Promising Antimalarial Scaffold.一项发散性的构效关系研究使得一种强效5-HT2c抑制剂优化为一种有前景的抗疟骨架。
ACS Med Chem Lett. 2012 Feb 9;3(5):373-7. doi: 10.1021/ml300008j. eCollection 2012 May 10.
2
Cyclopropyl Carboxamides: A New Oral Antimalarial Series Derived from the Tres Cantos Anti-Malarial Set (TCAMS).环丙基甲酰胺：源自特雷斯坎托斯抗疟药库（TCAMS）的新型口服抗疟药系列。
ACS Med Chem Lett. 2011 Aug 29;2(11):840-4. doi: 10.1021/ml2001517. eCollection 2011 Nov 10.
3
An Invitation to Open Innovation in Malaria Drug Discovery: 47 Quality Starting Points from the TCAMS.疟疾药物研发中的开放式创新邀请：来自TCAMS的47个优质起点
ACS Med Chem Lett. 2011 Aug 3;2(10):741-6. doi: 10.1021/ml200135p. eCollection 2011 Oct 13.
4
A new in vivo screening paradigm to accelerate antimalarial drug discovery.一种新的体内筛选范式，加速抗疟药物发现。
PLoS One. 2013 Jun 25;8(6):e66967. doi: 10.1371/journal.pone.0066967. Print 2013.
5
Assignment of the absolute configuration of polyfunctional compounds by NMR using chiral derivatizing agents.使用手性衍生试剂通过核磁共振确定多官能化合物的绝对构型
Chem Rev. 2012 Aug 8;112(8):4603-41. doi: 10.1021/cr2003344. Epub 2012 Jun 1.
6
P. falciparum in vitro killing rates allow to discriminate between different antimalarial mode-of-action.体外疟原虫杀伤率可用于区分不同的抗疟作用模式。
PLoS One. 2012;7(2):e30949. doi: 10.1371/journal.pone.0030949. Epub 2012 Feb 23.
7
Challenges in antimalarial drug discovery.抗疟药物研发的挑战。
Future Med Chem. 2011 Sep;3(11):1401-12. doi: 10.4155/fmc.11.91.
8
A randomized, double-blind, placebo-controlled study to investigate the safety, tolerability, and pharmacokinetics of single enantiomer (+)-mefloquine compared with racemic mefloquine in healthy persons.一项随机、双盲、安慰剂对照研究，旨在调查单一对映体 (+)-甲氟喹与消旋甲氟喹在健康人群中的安全性、耐受性和药代动力学。
Am J Trop Med Hyg. 2010 Dec;83(6):1195-201. doi: 10.4269/ajtmh.2010.10-0228.
9
Thousands of chemical starting points for antimalarial lead identification.数以千计的抗疟药物先导化合物化学起始点。
Nature. 2010 May 20;465(7296):305-10. doi: 10.1038/nature09107.
10
Artemisinin resistance in Plasmodium falciparum malaria.恶性疟原虫疟疾中的青蒿素耐药性。
N Engl J Med. 2009 Jul 30;361(5):455-67. doi: 10.1056/NEJMoa0808859.
Zotero 插件