Martin-Luther-Universität Halle-Wittenberg, Institut für Pharmazie, Wolfgang-Langenbeck-Straße 4, 06120 Halle (Saale), Germany.
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany.
Chem Commun (Camb). 2023 Apr 18;59(32):4697-4715. doi: 10.1039/d3cc00356f.
Tuberculosis is the leading bacterial killer worldwide. 8-Nitro-4-benzo[][1,3]thiazin-4-ones are a potent class of antitubercular agents with a new mechanism of action. BTZ043 and PBTZ169 (macozinone) have progressed to clinical studies. Herein, we give a comprehensive account of this important class of potential new drugs to treat tuberculosis. We present an overview of recent developments in the field of antitubercular benzothiazinones (BTZs) and summarize our own contributions. The review covers synthesis, structures and reactivity, mechanism of action, activity and structure activity relationships (SARs), physicochemical and pharmacokinetic properties as well as a brief summary of models and clinical studies. We address bioavailability issues and the challenge of the potentially toxic nitroaromatic moiety, including reactivity towards nucleophiles and highlight possible directions of further research into BTZs through chemical modification.
结核病是全球导致细菌死亡的主要原因。8-硝基-4-苯并[][1,3]噻嗪-4-酮是一类具有新型作用机制的强效抗结核药物。BTZ043 和 PBTZ169（macozinone）已进入临床研究阶段。本文全面介绍了这一类具有治疗结核病潜力的新型药物。本文综述了抗结核苯并噻嗪酮（BTZ）领域的最新进展，并总结了我们自己的研究成果。综述涵盖了合成、结构和反应性、作用机制、活性和构效关系（SAR）、物理化学和药代动力学特性以及模型和临床研究的简要总结。我们讨论了生物利用度问题和潜在毒性的硝基芳环部分的挑战，包括对亲核试剂的反应性，并强调了通过化学修饰进一步研究 BTZ 的可能方向。
