2. Academic Validation
  3. Design, synthesis and antibacterial properties of pyrimido[4,5-b]indol-8-amine inhibitors of DNA gyrase

Design, synthesis and antibacterial properties of pyrimido[4,5-b]indol-8-amine inhibitors of DNA gyrase

  • Bioorg Med Chem Lett. 2018 Sep 15;28(17):2998-3003. doi: 10.1016/j.bmcl.2018.05.049.
David H McGarry 1,  Ian R Cooper 2,  Rolf Walker 2,  Catherine E Warrilow 2,  Mark Pichowicz 2,  Andrew J Ratcliffe 2,  Anne-Marie Salisbury 2,  Victoria J Savage 2,  Emmanuel Moyo 2,  John Maclean 2,  Andrew Smith 2,  Cédric Charrier 2,  Neil R Stokes 2,  David M Lindsay 3,  William J Kerr 3
Affiliations

Affiliations

  • 1 Redx Pharma, Alderley Park, Cheshire SK10 4TG, United Kingdom. Electronic address: [email protected].
  • 2 Redx Pharma, Alderley Park, Cheshire SK10 4TG, United Kingdom.
  • 3 Department of Pure and Applied Chemistry, University of Strathclyde, WestCHEM, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.
PMID: 30122228 DOI: 10.1016/j.bmcl.2018.05.049
Abstract

According to the World Health Organization (WHO), approximately 1.7 million deaths per year are caused by tuberculosis infections. Furthermore, it has been predicted that, by 2050, Antibacterial resistance will be the cause of approximately 10 million deaths annually if the issue is not tackled. As a result, novel approaches to treating broad-spectrum Bacterial infections are of vital importance. During the course of our wider efforts to discover unique methods of targeting multidrug-resistant (MDR) pathogens, we identified a novel series of amide-linked pyrimido[4,5-b]indol-8-amine inhibitors of Bacterial type II topoisomerases. Compounds from the series were highly potent against gram-positive bacteria and mycobacteria, with excellent potency being retained against a panel of relevant Mycobacterium tuberculosis drug-resistant clinical isolates.

Keywords

Anti-infectives; DNA gyrase; ESKAPE pathogens; Pyrimido[4,5-b]indol-8-amine; Topoisomerases.

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