Synthesis, characterization and biological activity of the 3-nitro isomer of bioreductive TB drug pretomanid (PA-824)

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dc.contributor.author Bonnet, M en
dc.contributor.author Thompson, Andrew en
dc.contributor.author Lee, Ho en
dc.contributor.author Franzblau, SG en
dc.contributor.author Wan, B en
dc.contributor.author Wong, GS en
dc.contributor.author Cooper, CB en
dc.contributor.author Denny, William en
dc.coverage.spatial Regensburg, Germany en
dc.date.accessioned 2018-10-11T23:03:21Z en
dc.date.issued 2017-09-05 en
dc.identifier.uri http://hdl.handle.net/2292/41101 en
dc.description.abstract (See Tue - P46 in URL above). Tuberculosis (TB) is still a major global public health threat – a persistent epidemic that currently afflicts over 11 million people worldwide. Although TB can be treated, the lengthy and complex treatment regimens are inadequate to contain the disease, especially its multidrug resistant (MDR) forms. Very few new drugs have been developed in the past 50 years, and there is a need for anti-TB agents with different modes of action. The nitroimidazooxazine Pretomanid (PA-824, 1) is representative of a new class of bioreductive TB drugs and is currently undergoing Phase II/III clinical trials as part of a novel combination of agents (with bedaquiline, moxifloxacin and pyrazinamide) which can potentially reduce treatment duration and complexity. During the course of our studies, we became interested in the biological activity of the 3-nitro isomer of Pretomanid (2). The synthesis of 2 proved to be very challenging. The key and limiting step of the synthesis was a nitration reaction, involving the dihydro-imidazooxazinol intermediate 3. We report here our optimization of the synthetic route, allowing us to prepare 10 g of the desired final target 2. The structure of 2 was confirmed by X-ray crystallography. Preliminary data on its biological activity are also reported. en
dc.relation.ispartof 26th International Society of Heterocyclic Chemistry Congress en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Synthesis, characterization and biological activity of the 3-nitro isomer of bioreductive TB drug pretomanid (PA-824) en
dc.type Conference Poster en
dc.rights.holder Copyright: The author en
pubs.author-url http://www-oc.chemie.uni-regensburg.de/ISHC2017/download/ISHC2017_Book_of_Abstracts.pdf en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.elements-id 700560 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Auckland Cancer Research en
pubs.org-id Science en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
pubs.record-created-at-source-date 2017-10-25 en


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