WuXi AppTec, 666 Gaoxin Road, East Lake High-tech Development Zone, Wuhan 430075, China.
WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
Bioorg Med Chem Lett. 2022 Sep 15;72:128871. doi: 10.1016/j.bmcl.2022.128871. Epub 2022 Jun 28.
Multidrug-resistant pulmonary tuberculosis (MDR-TB) is a major health problem worldwide. The treatment for MDR-TB requires medications for a long duration (up to 20-24 months) with second-line drugs resulting in unfavorable outcomes. Nitroimidazoles are promising antimycobacterial agents known to inhibit both aerobic and anaerobic mycobacterial activity. Delamanid and pretomanid are two nitroimidazoles approved by the regulatory agencies for MDR-TB treatment. However, both agents possess unsatisfactory absorption and QTc prolongation. In our search for a safer nitroimidazole, we discovered JBD0131 (2). It exhibited excellent anti-mycobacterial activity against M. tuberculosis H37Rv in vitro and in vivo, improved PK and absorption, reduced QT prolongation potential of delamanid. JBD0131 is currently in clinical development in China for pulmonary tuberculosis (CTR20202308).
耐多药肺结核（MDR-TB）是全球范围内的一个主要健康问题。MDR-TB 的治疗需要使用多种药物进行长期治疗（长达 20-24 个月），二线药物的使用导致治疗效果不佳。硝基咪唑类药物是一种有前途的抗分枝杆菌药物，已知可抑制需氧和厌氧分枝杆菌的活性。德拉马尼和普托马尼德是两种已被监管机构批准用于 MDR-TB 治疗的硝基咪唑类药物。然而，这两种药物的吸收和 QTc 延长都不理想。在寻找更安全的硝基咪唑类药物的过程中，我们发现了 JBD0131（2）。它在体外和体内均表现出对结核分枝杆菌 H37Rv 的优异抗分枝杆菌活性，改善了药代动力学和吸收，降低了德拉马尼德的 QT 延长潜力。JBD0131 目前正在中国进行肺结核（CTR20202308）的临床开发。
