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Spectrophotometric determination of two N-(4-quinolyl) anthranilic acid derivative (glafenine and floctafenine).

Spectrophotometric methods were developed for the determination of glafenine and floctafenine. The first method depends upon the determination of glafenine in raw material and tablets as well as in the presence of its main degradation product glafenic acid (up to 40%). Differential first derivative spectral response at 245 nm in 0.1 N hydrochloric acid, where the corresponding degradation product exhibits no contribution in 0.1 N sodium hydroxide. The method allows the determination of 2.5-30 microg ml(-1). The second method depends upon the reaction of floctafenine with 2,3-dichloro 5,6-dicyano-p-benzoquinone (DDQ) in acetonitrile to give highly colored complex that could be measured quantitatively at (about) lambda(max) 538 nm. The method permits the determination of 40-180 microg ml(-1) or by measuring the first derivative spectral response of the color at 610 nm. The method permits the determination of floctafenine in presence of thiocolchicoside. The methods mentioned both simplicity and sensitivity, having excellent precision and accuracy (100.31 +/- 0.63, 100.78 +/- 0.77 and 99.90 +/- 0.56 for glafenine and floctafenine, respectively). The results were of comparable accuracy and reproducibility with the reported methods.

Analgesics, Non-Narcotic↗

QSAR study on inhibition of brain 3-hydroxy-anthranilic acid dioxygenase (3-HAO): a molecular connectivity approach.

The ability of 4,5-, 4,6-disubstituted and 4,5,6-trisubstituted 3-hydroxyanthranilic acid derivatives to reduce the production of the excitotoxin quinolinic acid (QUIN) by inhibition of brain 3-hydroxyanthranilic acid dioxygenase (3-HAO) has been investigated using molecular connectivity indices (0chi(v), 1chi(v), 2chi(v)). The in-vivo inhibition of 3-HAO in rat cortex (pIC(50), nM) is used for this purpose. The regression models obtained suggest that the degree of branching of the compounds under study have a dominant role in the observed inhibition potency. The data were used to generate quantitative structure-activity relationship (QSAR) models for estimating the potency of 3-HAO. The information obtained from the correlation should be useful in designing more potent analogues.

3-Hydroxyanthranilate 3,4-Dioxygenase↗

Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors.

Two readily synthesized anthranilamide, VEGF receptor tyrosine kinase inhibitors have been prepared and evaluated as angiogenesis inhibitors. 2-[(4-Pyridyl)methyl]amino-N-[3-(trifluoromethyl)phenyl]benzamide (5) and N-3-isoquinolinyl-2-[(4-pyridinylmethyl)amino]benzamide (7) potently and selectively inhibit recombinant VEGFR-2 and VEGFR-3 kinases. As a consequence of their physicochemical properties, these anthranilamides readily penetrate cells and are absorbed following once daily oral administration to mice. Both 5 and 7 potently inhibit VEGF-induced angiogenesis in an implant model, with ED(50) values of 7 mg/kg. In a mouse orthotopic model of melanoma, 5 and 7 potently inhibited both the growth of the primary tumor as well as the formation of spontaneous peripheral metastases. The anthranilamides 5 and 7 represent a new structural class of VEGFR kinase inhibitors, which possess potent antiangiogenic and antitumor properties.

Administration, Oral↗

Anaerobic degradation of 2-aminobenzoate (anthranilic acid) by denitrifying bacteria.

In the presence of oxygen many aminoaromatic compounds polymerize to form recalcitrant macromolecules. To circumvent undesirable oxidation reactions, the anaerobic biodegradation of a simple member of this class of compounds was investigated. Two strains of bacteria were isolated which degrade 2-aminobenzoate anaerobically under denitrifying conditions, with nitrate as the terminal electron acceptor. Both organisms, which were assigned to the genus Pseudomonas, oxidized 2-aminobenzoate completely to CO2 and NH4+. Nitrate was reduced to nitrite. When nitrate was deplete from the growth medium the accumulated nitrite was reduced to nitrogen. The results establish a model system for the anaerobic, rapid, and complete oxidation of an aminoaromatic compound.

Anaerobiosis↗