Synthetic approaches towards bedaquiline and its derivatives

Matthew B Calvert; Daniel P Furkert; Christopher B Cooper; Margaret A Brimble

doi:10.1016/j.bmcl.2020.127172

Synthetic approaches towards bedaquiline and its derivatives

Bioorg Med Chem Lett. 2020 Jun 15;30(12):127172. doi: 10.1016/j.bmcl.2020.127172. Epub 2020 Apr 7.

Authors

Matthew B Calvert¹, Daniel P Furkert², Christopher B Cooper³, Margaret A Brimble⁴

Affiliations

¹ School of Chemical Sciences, The University of Auckland, Symonds Street, Auckland 1010, New Zealand.
² School of Chemical Sciences, The University of Auckland, Symonds Street, Auckland 1010, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Symonds Street, Auckland 1010, New Zealand.
³ Global Alliance for TB Drug Development, 40 Wall Street, New York, NY 10005, USA.
⁴ School of Chemical Sciences, The University of Auckland, Symonds Street, Auckland 1010, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Symonds Street, Auckland 1010, New Zealand. Electronic address: m.brimble@auckland.ac.nz.

PMID: 32291133
DOI: 10.1016/j.bmcl.2020.127172

Abstract

Bedaquiline is a diarylquinoline drug that demonstrates potent and selective inhibition of mycobacterial ATP synthase, and is clinically administered for the treatment of multi-drug resistant tuberculosis. Due to its excellent activity and novel mechanism of action, bedaquiline has been the focus of a number of synthetic studies. This review will discuss these synthetic approaches, as well as the synthesis and bioactivity of the numerous derivatives and molecular probes inspired by bedaquiline.

Keywords: Bedaquiline; Diarylquinolines; SAR; Stereoselective synthesis; Tuberculosis.

Publication types

Review

MeSH terms

Alkynes / chemistry
Animals
Antitubercular Agents / chemical synthesis*
Azides / chemistry
Catalysis
Cycloaddition Reaction
Diarylquinolines / chemical synthesis*
Drug Evaluation, Preclinical
Humans
Molecular Structure
Mycobacterium tuberculosis / drug effects*
Stereoisomerism
Structure-Activity Relationship
Triazoles / chemistry
Tuberculosis, Multidrug-Resistant / drug therapy*

Substances

Alkynes
Antitubercular Agents
Azides
Diarylquinolines
Triazoles
bedaquiline