Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Northern Border University, Rafha, Saudi Arabia.
Department of Biological Sciences, Faculty of Science, Northern Border University, Arar, Saudi Arabia.
Expert Opin Ther Pat. 2021 Aug;31(8):759-772. doi: 10.1080/13543776.2021.1902990. Epub 2021 Apr 13.
In recent years, the advent of multidrug-resistant tuberculosis (MDR-TB), the extensively-resistant TB (XDR-TB), and the total drug-resistant-TB (TDR-TB) have led the community to develop new antitubercular molecules. The decaprenylphosphoryl-β-D-ribose-2'-epimerase-1 (DprE1) is an established target to developed new anti-TB drugs. This enzyme is required to synthesize the cell wall of (Mtb).
This patent review focuses on the granted patents and patent applications related to the chemical entities developed as DprE1 inhibitors for TB treatment from the publication year of the BTZ-043 compound patent application (2007) till 30 September 2020.
The DprE1 has many advantages in the development of new antitubercular molecules, for example, its location in the periplasm of the Mtb cell wall and its absence in the human body. This indicates that the DprE1 inhibitors are selective for Mtb, and their toxic and side effects on the human body may be negligible or small. Accordingly, the use of DprE1 inhibitors may be benefic for patients with drug-resistant bacteria that require long-term medication. Four molecules are in clinical trials, which could become the drugs of the future for TB-therapy.
近年来，耐多药结核病（MDR-TB）、广泛耐药结核病（XDR-TB）和完全耐药结核病（TDR-TB）的出现促使人们开发新的抗结核分子。脱磷酸烯醇式丙酮酸-β-D-核糖基-2′-差向异构酶-1（DprE1）是开发新抗结核药物的既定靶点。该酶是合成（Mtb）细胞壁所必需的。
本专利综述重点关注自 BTZ-043 化合物专利申请（2007 年）公布以来，截至 2020 年 9 月 30 日，与作为抗结核治疗的 DprE1 抑制剂开发相关的已授权专利和专利申请。
DprE1 在开发新的抗结核分子方面具有许多优势，例如其位于 Mtb 细胞壁的周质中，而在人体中不存在。这表明 DprE1 抑制剂对 Mtb 具有选择性，它们对人体的毒性和副作用可能微不足道或很小。因此，使用 DprE1 抑制剂可能对需要长期药物治疗的耐药菌患者有益。目前有四种分子正在临床试验中，它们可能成为未来结核病治疗的药物。
