Synthesis of 3-(Pyridin-2-yl)quinazolin-2,4(1H,3H)-diones via Annulation of Anthranilic Esters with N-pyridyl Ureas.

A new route for the synthesis of quinazolin-2,4(1H,3H)-diones and thieno [2,3-d]pyrimidine-2,4(1H,3H)-diones substituted by pyridyl/quinolinyl moiety in position 3 has been developed. The proposed method concluded in an annulation of substituted anthranilic esters or 2-aminothiophene-3-carboxylates with 1,1-dimethyl-3-(pyridin-2-yl) ureas. The process consists of the formation of N-aryl-N'-pyridyl ureas followed by their cyclocondensation into the corresponding fused heterocycles. The reaction does not require the use of metal catalysts and proceeds with moderate to good yields (up to 89%). The scope of the method is more than 30 examples, including compounds with both electron-withdrawing and electron-donating groups, as well as diverse functionalities. At the same time, strong electron-acceptor substituents in the pyridine ring of the starting ureas reduce the product yield or even prevent the cyclocondensation step. The reaction can be easily scaled to gram quantities.

Synthesis and anti-inflammatory evaluation of N-sulfonyl anthranilic acids via Ir(III)-catalyzed C-H amidation of benzoic acids.

The iridium(III)-catalyzed ortho-C-H amidation of benzoic acids with sulfonyl azides is described. These transformations allow the facile generation of N-sulfonyl anthranilic acids, which are known as crucial scaffolds found in biologically active molecules. In addition, all synthetic products were evaluated for in vitro anti-inflammatory activity against interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2) with lipopolysaccharide (LPS)-induced RAW264.7 cells. Notably, compounds 4c and 4d, generated from p-OMe- and p-Br-sulfonyl azides, were found to display potent anti-inflammatory property stronger than that of well-known NSAIDs ibuprofen.

A spectroscopic study of substituted anthranilic acids as sensitive environmental probes for detecting cancer cells.

Small-molecule fluorescent reporters of disease states are highly sought after, yet they remain elusive. Anthranilic acids are extremely sensitive environmental probes, and hold promise as general but selective agents for cancer-cell detection if they can be equipped with the appropriate targeting groups. The optical properties of a small library of N-isopropyl invariant anthranilic acids were investigated in methanol and chloroform. Points of variation included: fluoro, trifluoromethyl, or cyano substitution on the aromatic ring, and derivitization of the parent carboxylic acid as esters or secondary carboxamides. Phenylboronic acid conjugation at the carboxylic acid alongside un-, mono-, and dimethylated 2-amino groups was also explored. The boron-containing anthranilic acids were also evaluated as sensitive fluorescent probes for cancer cells using laser scanning confocal microscopy. In general, the compounds produced blue fluorescence that was strongly influenced by substitution and environment. 4-Trifluoromethyl and 4-cyano esters proved to be the most sensitive environmental probes with quantum yields as large as 100% in chloroform, and enhancements of up to 30-fold on going from methanol to chloroform. Stokes shifts ranged from 63 to 120nm, generally increasing with ortho-substitution and environmental polarity. It was demonstrated that phenylboronic acid conjugation was an attractive method for cancer cell detection via boronate ester formation with overexpressed glycoproteins (with no interference from normal, healthy cells), presumably due to favorable boron-sialic acid interactions.

Negative regulation on allograft immune response induced with up-regulated expression of IDO mediated by 3,4-DAA / 中华器官移植杂志

Objective To investigate role of N-(30,40-dimethoxycinnamonyl) anthranilic acid (3,4-DAA) in mediating the negative immune regulation by indoleamine 2,3-dioxygenase in mice skin transplantation.Method The mice skin transplant model was established.T lymphocytes were isolated from mice splenocytes,and serum was collected.ELISA was applied to detect the IL-2 and IFN-γ concentrations in culture supernates of mice spleen lymphocytes and serum.Flow cytometry was applied to examine the phenotypes of T lymphocytes and RT-PCR to analyze the IDO mRNA transcription.Results T lymphocyte proliferation was significantly decreased by 3,4-DAA and the concentrations of IL-2 and IFN-γ were apparently decreased in 3,4-DAA group as compared with those in control group.The percentages of CD3 +,CD4 + and CD8 + T lymphocytes were lower,and the percentage of CD4 + CD25 + T lymphocytes was higher in 3,4-DAA disposal group than in control group,but there was no significant difference.IDO mRNA expression showed obvious increase in 3,4-DAA group as compared with control group.Conclusion 3,4-DAA can up-regulate the IDO expression to induce the increasing metabolism of tryptophan,subsequently inhibiting T cell proliferation and showing specific property of negative immune regulation.

Research on the Extraction and Purification of Organic Acids from Folium Isatidis with Macroporous Adsorptive Resin / 中国药房

OBJECTIVE:To extract and purify organic acids with macroporous resins from Folium Isatidis.METHODS:Folium Isatidis was extracted with 70% aqueous ethanol(pH=2)by Soxhlet extraction.The process was optimized by employing orthogonal test design with the content of anthranilic acid as the index.RESULTS:The resin HPD100 had much better adsorption capacity and desorption ratio by using 3 BV 60% aqueous ethanol to extract organic acids in Folium Isatidis than other resins.The results showed that HPD100 possessed the better ecomic under the concentration of sample 0.18mg?mL-1,the condition of pH 3.5,and flowing rate of 2BV?h-1.CONCLUSION:Macroporous resin HPD100 may be value of isolating and purifying the organic acids from Folium Isatidis.