dc.contributor.author |
Thompson, Andrew |
en |
dc.contributor.author |
Blaser, Adrian |
en |
dc.contributor.author |
Anderson, Robert |
en |
dc.contributor.author |
Shinde, Sujata |
en |
dc.contributor.author |
Franzblau, SG |
en |
dc.contributor.author |
Ma, Z |
en |
dc.contributor.author |
Denny, William |
en |
dc.contributor.author |
Palmer, Brian |
en |
dc.date.accessioned |
2011-11-18T02:17:17Z |
en |
dc.date.issued |
2009 |
en |
dc.identifier.citation |
Journal of Medicinal Chemistry 52(3):637-645 2009 |
en |
dc.identifier.issn |
0022-2623 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/9390 |
en |
dc.description.abstract |
The nitroimidazooxazine S-1 (PA-824) is a new class of bioreductive drug for tuberculosis. A series of related bicyclic nitroheterocycles was synthesized, designed to have a wide range of one-electron reduction potentials E(1) (from −570 to −338 mV, compared with −534 mV for S-1). The observed E(1) values closely correlated with the σm values of the heteroatom at the 4/8-position of the adjacent six-membered ring. Although the compounds spanned a range of E(1) values around that of S-1, only the nitroimidazothiazines showed significant antitubercular activity (at a similar level of potency), suggesting that E(1) is not the main driver of efficacy. Furthermore, there was a correlation between activity and the formation of imidazole ring-reduced products at the two-electron level, pointing to the potential importance of this reduction pathway, which is determined by the nature of the substituent at the 2-position of the 4-nitroimidazole ring. |
en |
dc.language |
EN |
en |
dc.publisher |
American Chemical Society |
en |
dc.relation.ispartofseries |
Journal of Medicinal Chemistry |
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. Details obtained from
http://www.sherpa.ac.uk/romeo/issn/0022-2623/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
ONE-ELECTRON REDUCTION |
en |
dc.subject |
MYCOBACTERIUM-TUBERCULOSIS |
en |
dc.subject |
NITROIMIDAZOPYRAN PA-824 |
en |
dc.subject |
AQUEOUS-SOLUTION |
en |
dc.subject |
MURINE MODEL |
en |
dc.subject |
IN-VITRO |
en |
dc.subject |
VOLTAMMETRIC DETERMINATION |
en |
dc.subject |
PULSE-RADIOLYSIS |
en |
dc.subject |
RADICALS |
en |
dc.subject |
AGENTS |
en |
dc.title |
Synthesis, reduction potentials and anti-tubercular activity of ring A/B analogues of the bioreductive drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824). |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1021/jm801087e |
en |
pubs.issue |
3 |
en |
pubs.begin-page |
637 |
en |
pubs.volume |
52 |
en |
dc.rights.holder |
Copyright: American Chemical Society |
en |
dc.identifier.pmid |
19099398 |
en |
pubs.end-page |
645 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
88882 |
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 |
2010-09-01 |
en |
pubs.dimensions-id |
19099398 |
en |