Details
Stereochemistry | ACHIRAL |
Molecular Formula | C16H13N3O4 |
Molecular Weight | 311.2921 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN1C(=O)N(C2=CC(=CC=C2)[N+]([O-])=O)C3=C(C=CC=C3)C1=O
InChI
InChIKey=GNWCRBFQZDJFTI-UHFFFAOYSA-N
InChI=1S/C16H13N3O4/c1-2-17-15(20)13-8-3-4-9-14(13)18(16(17)21)11-6-5-7-12(10-11)19(22)23/h3-10H,2H2,1H3
Nitraquazone (TVX 2706) is an phosphodiesterase inhibitor with antiinflammatory action. It strongly enhances the increase in intracellular levels of cyclic AMP caused by appropriate effectors in all systems tested so far. EC50 values are in the submicromolar range. The effect is apparently neither due to an increased responsiveness of the hybrid cells for an effector like prostaglandin E1 nor to an increased activity of adenylate cyclase, but to an inhibition of both low and high affinity cyclic AMP phosphodiesterases. Half-maximal inhibition of enzyme activity is obtained at 10 uM TVX 2706. TVX 2706 does not interfere with the calmodulin activation of phosphodiesterase. Nitraquazone affected cytokine production by PHA-stimulated human blood cells. Nitraquazone was active in reducing the production of IL-5 (IC50 = 0.8 uM), while its potency against IL-2, GM-CSF and IFN-gamma was 3-6 times lower.
Approval Year
PubMed
Title | Date | PubMed |
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Modulation of TNF alpha and IL-1 beta from endotoxin-stimulated monocytes by selective PDE isozyme inhibitors. | 1993 |
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Cytokine production by phytohemagglutinin-stimulated human blood cells: effects of corticosteroids, T cell immunosuppressants and phosphodiesterase IV inhibitors. | 1995 Sep |
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Characterization of phosphodiesterase 4 in guinea-pig macrophages: multiple activities, association states and sensitivity to selective inhibitors. | 1998 May |
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Phosphodiesterase 4 inhibitors, structurally unrelated to rolipram, as promising agents for the treatment of asthma and other pathologies. | 2000 May |
Patents
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9630352
Curator's Comment: The cyclic AMP phosphodiesterases (PDE) in guinea-pig peritoneal macrophages were isolated, partially characterized and their role in regulating the cyclic AMP content in intact cells evaluated. Approximately 90% of the PDE activity was membrane-bound and exclusively hydrolyzed cyclic AMP. This activity was not removed by KCl (200 mM) but was readily solubilized by the non-ionic detergent, Triton X-100 (1% v/v).
Greater than 80% of the hydrolytic activity was suppressed by the PDE4 inhibitor nitraquazone with IC50 of 540 nM.
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C744
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ACTIVE MOIETY