| Identification | Back Directory | [Name]
PA 824 | [CAS]
187235-37-6 | [Synonyms]
PA 824
CS-930
EOS-60675
(S)-PA 824
PRETOMANID
PA-824, >=98%
Pretomanid（PA-824）
PA-824(Pretomanid)
PA-824;PA824;PA 824
PRETOMANID;(S)-PA 824
(S)-PA 824 (Pretomanid)
2-NITRO-6(S)-[4-(TRIFLUOROMETHOXY)BENZYLOXY]-6,7-DIHYDRO-5H-IMIDAZO[2,1-B][1,3]OXAZINE
(S)-6-(4-(trifluoromethoxy)benzyloxy)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
(6S)-2-nitro-6-{[4-(trifluoromethoxy)phenyl]metho
xy}-5H,6H,7H-imidazo[2,1-b][1,3]oxazine
(S)-6,7-Dihydro-2-nitro-6-[[4-(trifluoromethoxy)phenyl]methoxy]-5H-imidazo[2,1-b][1,3]oxazine
(6S)-6,7-Dihydro-2-nitro-6-[[4-(trifluoromethoxy)phenyl]methoxy]-5H-imidazo[2,1-b][1,3]oxazine
(6S)-2-Nitro-6-[[4-(trifluoromethoxy)phenyl]methoxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
(S)-2-Nitro-6-((4-(trifluoromethoxy)benzyl)oxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine 98+%
5H-IMidazo[2,1-b][1,3]oxazine, 6,7-dihydro-2-nitro-6-[[4-(trifluoroMethoxy)phenyl]Methoxy]-, (6S)-
(6S)-6,7-Dihydro-2-nitro-6-[[4-(trifluoromethoxy)phenyl]methoxy]-5H-imidazo[2,1-b][1,3]oxazine PA-824 | [EINECS(EC#)]
1533716-785-6 | [Molecular Formula]
C14H12F3N3O5 | [MDL Number]
MFCD06809939 | [MOL File]
187235-37-6.mol | [Molecular Weight]
359.257 |
| Chemical Properties | Back Directory | [Melting point ]
149-150℃ | [Boiling point ]
462.3±55.0 °C(Predicted) | [density ]
1.58 | [storage temp. ]
-20°C | [solubility ]
DMSO (Slightly), Methanol (Slightly) | [form ]
powder | [pka]
-0.67±0.40(Predicted) | [color ]
white to brown | [optical activity]
[α]/D -40 to -48°, c = 1 in methanol |
| Hazard Information | Back Directory | [Uses]
A novel anti-tuberculosis drug. | [Biological Activity]
pa-824, a bicyclic nitroimidazoles, is an anti-tuberculosis (tb) agent that exerts potent in vitro activity against mycobacterium tuberculosis with the minimal inhibition concentration (mic) ranging from 0.015 μg/ml to 0.25 μg/ml and remains actively against a wide range of isolates that are resistant to commonly used anti-tb agents leading to its successful application in the treatment of tb [1].pa-824 has been found to exhibit bactericidal activity against replicating bacilli and non-replicating bacilli under hypoxic or prolonged culture conditions in a dose dependent fashion through two possible mechanisms, which include pa-824 induced inhibition of ketomycolate synthesis and pa-824 mediated donation of nitric oxide during enzymatic nitro-reduction [1]. | [Biochem/physiol Actions]
PA-824 is an anti-tuberculosis drug. | [Synthesis]
Pretomanid can be produced as follow
 | [Enzyme inhibitor]
This first-in-class tuberculosis pro-drug (FW = 359.26 g/mol; CAS 187235-
37-6), also named (6S) -2-nitro-6-{[4- (trifluoromethoxy) -benzyl]oxy}-6,7-
dihydro-5H-imidazo[2,1-b][1,3]oxazine, is active against both replicating
and hypoxic, non-replicating forms of Mycobacterium tuberculosis. After
activation by a process that depends on M. tuberculosis F420 cofactor, PA-
824 exerts its bacteriocidal action by inhibiting protein biosynthesis and cell
wall lipid synthesis. Its reduction potential does not appear to be the
main driver for inhibitor efficacy. Significantly, PA-824 generates a des-
nitro metabolite, along with a reactive nitrogen species (including nitric
oxide), that may be effectors of the anaerobic activity of these compounds
. Furthermore, nitric oxide scavengers protected M. tuberculosis from the
lethal effects of the drug. This finding suggests PA-824 releases a lethal
nitrogen oxide-like metabolite that factors into its bacteriocidal action. That
PA-824 is without effect on M. leprae is consistent with the absence of a
required activating enzyme, namely nitroimidazo-oxazine-specific
nitroreductase (encoded by Rv3547), in the M. leprae genome. | [References]
[1] ahmad z, peloquin ca, singh rp, derendorf h, tyagi s, ginsberg a, grosset jh, nuermberger el. pa-824 exhibits time-dependent activity in a murine model of tuberculosis. antimicrob agents chemother. 2011 jan;55(1):239-45. doi: 10.1128/aac.00849-10. epub 2010 oct 11. |
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