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Nitroimidazoles for the treatment of TB: past present and future

机译:硝基咪唑类药物治疗结核病的过去现在和未来

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摘要

Tuberculosis remains a leading cause of death resulting from an infectious agent, and the spread of multi- and extensively drug-resistant strains of Mycobacterium tuberculosis poses a threat to management of global health. New drugs that effectively shorten the duration of treatment and are active against drug-resistant strains of this pathogen are urgently required to develop effective chemotherapies to combat this disease. Two nitroimidazoles, PA-824 and OPC-67683, are currently in Phase II clinical trials for the treatment of TB and the outcome of these may determine the future directions of drug development for anti-tubercular nitroimidazoles. In this review we summarize the development of these nitroimidazoles and alternative analogs in these series that may offer attractive alternatives to PA-824 and OPC-67683 for further development in the drug-discovery pipeline. Lastly, the potential pitfalls in the development of nitroimidazoles as drugs for TB are discussed.
机译:结核病仍然是由传染原导致的主要死亡原因,结核分枝杆菌的多药耐药株和广泛耐药株的传播对全球健康管理构成威胁。迫切需要能有效缩短治疗持续时间并对这种病原体的耐药菌株具有活性的新药,以开发出有效的化学疗法来对抗这种疾病。目前,两种硝基咪唑PA-824和OPC-67683正在治疗TB的II期临床试验中,这些结果可能决定抗结核硝基咪唑药物开发的未来方向。在本综述中,我们总结了这些硝基咪唑及其替代类似物的开发情况,它们可能为PA-824和OPC-67683提供有吸引力的替代物,以便在药物开发管道中进一步开发。最后,讨论了硝基咪唑类药物作为结核病药物开发的潜在陷阱。

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