Synthetic molecules as DprE1 inhibitors: A patent review

ABSTRACT

Introduction

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-2ʹ-epimerase-1 (DprE1) is an established target to developed new anti-TB drugs. This enzyme is required to synthesize the cell wall of Mycobacterium tuberculosis (Mtb).

Area Covered

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.

Expert Opinion

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.

KEYWORDS:

• Azaindole
• benzothiazinone
• dpre1 inhibitors
• patent review
• synthetic molecules
• tuberculosis

ARTICLE HIGHLIGHTS

• The DprE1 is an established target to develop anti-tubercular drugs

• Many patents/patent applications on the synthetic molecules as DprE1 inhibitors have been published

• DprE1 inhibitors may tackle the problems of drug-resistant tuberculosis that require long-term medication

• Four DprE1 inhibitors are in clinical trials as anti-tubercular agents

• The drugs targeting DprE1 can be drugs of the future for the TB-therapy

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work did not receive any funding.