Application of Deep Eutectic Solvents in the Synthesis of Substituted 2-Mercaptoquinazolin-4(3H)-Ones: A Comparison of Selected Green Chemistry Methods

In this study, deep eutectic solvents (DESs) were used as green and eco-friendly media for the synthesis of substituted 2-mercaptoquinazolin-4(3H)-ones from different anthranilic acids and aliphatic or aromatic isothiocyanates. A model reaction on anthranilic acid and phenyl isothiocyanate was performed in 20 choline chloride-based DESs at 80 °C to find the best solvent. Based on the product yield, choline chloride:urea (1:2) DES was found to be the most effective, while DESs acted both as solvents and catalysts. Desired compounds were prepared with moderate to good yields using stirring, microwave-assisted, and ultrasound-assisted synthesis. Significantly, higher yields were obtained with mixing and ultrasonication (16–76%), while microwave-induced synthesis showed lower effectiveness (13–49%). The specific contribution of this research is the use of DESs in combination with the above-mentioned green techniques for the synthesis of a wide range of derivatives. The structures of the synthesized compounds were confirmed by 1H and 13C NMR spectroscopy.

Novel Niacin Receptor Agonists: A Promising Strategy for the Treatment of Dyslipidemia.

Background: Hyperlipidemia is characterized by high level of cholesterol and triglycerides in blood. Various classes of drugs like statins, fibrates, niacin etc. are used for treatment of hyperlipidaemia. Objective: Niacin, which is one of the beneficial anti-hyperlipidemic agents, helps to lower LDL cholesterol by 20 to 40% and causes increase of HDL cholesterol by 20 to 35%. However cutaneous flushing, loss of glucose tolerance, liver toxicity are the reported side effects of niacin therapy responsible for decreased patient compliance. Very recently, the G protein coupled receptor (GPCR); GPR109A located on the adipocytes has been identified as the receptor for activation of niacin. Method: In-vitro studies have demonstrated that GPR109A receptor having high affinity for niacin. The present review attempts to provide a systematic presentation of the various chemical classes of compounds that have been reported as novel niacin receptor agonists including pyrazole-3-carboxylic acids, urea derivatives, anthranilic acids, biaryl anthranilides, tetrahydro anthranilic acid, xanthines, barbituric acid, bicyclic pyrazole carboxylic acids, pyrido pyrimidinones, pyrazolyl propionyl cyclohexenamides, pyrazole acids etc. Results : As the design of GPR109A receptor agonists offers a promising solution for treatment of dyslipidemia, this review will be beneficial for medicinal and drug discovery chemists to expediate the process of discovery of new class of antihyperlipidemic agent with favorable lipid lowering profile with increase in HDL levels. Conclusion: This review explains about novel GPR109A receptor agonist for the treatment of dyslipidemia.

Selenium-catalyzed intramolecular atom- and redox-economic transformation of o-nitrotoluenes to anthranilic acids

Anthranilic acids (AAs) are significant basic chemicals for pharmaceuticals, agrochemicals, dyes, fragrances, etc. Superfluous steps are always involved to obtain the AAs. Herein, we demonstrate a straightforward strategy to transform...

A practical route to 2-iodoanilines via transition-metal-free and base-free decarboxylative iodination of anthranilic acids under oxygen

A simple and practical procedure for the synthesis of 2-iodoanilines has been developed. A series of highly regioselective 2-iodoanilines was obtained in satisfactory to good yield (up to 90%) by...

Intermolecular interactions of apple pectin modified by pharmacophores with iodine and antimicrobial activity of iodine-containing pectin materials

New complex compounds based on apple pectin and pharmacologically active organic acids (nicotinic, salicylic, 5-aminosalicylic and anthranilic acids) were synthesized. The obtained complexes were characterized by a number of physicochemical research methods (UV, IR, and 13C NMR spectroscopy, electron microscopy, viscosimetry, polarimetry, and elemental analysis). Based on pharmacophore-containing pectins, stable iodine-containing films were obtained. The effect of the structure of a polysaccharide-modifying drug compound on the properties of iodine-containing polymeric materials was shown: iodine content, time of release of iodine from the film, diffusion and surface characteristics. The formation of a new set of properties in the production of iodine-containing films based on pharmacophore-containing pectins provides an increase in antimicrobial activity by 1.3-1.5 times in comparison with the initial polymer matrices.

COMPLEXATION OF APPLE PECTIN, MODIFIED TO PHARMACOPHORE, WITH THE CATIONS MANGANESE (II) IN AQUEOUS SOLUTIONS

Complex formation in systems containing manganese (II), natural pectin and/or pectin modified by organic pharmacophores (nicotine, salicylic, 5-aminosalicylic, anthranilic acids) was studied by spectral (UV-, IR-, NMR 13C spectroscopy), potentiometric and viscometric methods. Method isomolar series and the molar relationship defined by the molar composition and the range of stability of metal complexes: pectin + nicotinic acid > pectin + acid 5-aminosalicylic > pectin + anthranilic acid > pectin + salicylic acid > native pectin. It is shown that the stability constant of metal complexes is significantly influenced by the reaction temperature and the structure of the pharmacophore. The presence of an amino group in the structure of an aromatic molecule increases the stability of metal complexes by 1.5–2 orders of magnitude. The standard thermodynamic characteristics (∆Hº; ∆Gº; ∆Sº) are calculated, which indicate that the processes of complexation in all cases are enthalpy-entropy favorable (∆Hº<0, ∆Sº>0) and proceed spontaneously (∆Gº<0). The influence of the structure of the drug compound in the polymer ligand on a number of physical and chemical properties of metal complexes was revealed. The data of NMR 13C and IR-spectra allow us to conclude that not only carboxyl groups but also hydroxyl functions of polymer matrices participate in the coordination interaction of pectin and/or pharmacophore-containing pectin with manganese (II) cations.

Redox-neutral decarboxylative photocyclization of anthranilic acids

A mild redox-neutral catalyst- and oxidant-free photoredox system was found to enable decarboxylative cyclization of anthranilic acids.

4H-Benzo[d][1,3]oxazin-4-ones and Dihydro Analogs from Substituted Anthranilic Acids and Orthoesters

A one-pot route to 2-alkyl and 2-aryl-4H-benzo[d][1,3]oxazin-4-ones (also known as 4H-3,1-benzoxazin-4-ones) has been developed and studied. The method involves the reaction of aryl-substituted anthranilic acids with orthoesters in ethanol catalyzed by acetic acid. Additionally, we have also investigated the reaction under microwave conditions. Not all of the substrates were successful in yielding the target heterocycles as some of the reactions failed to undergo the final elimination. This process led to the isolation of (±)-2-alkyl/aryl-2-ethoxy-1,2-dihydro-4H-benzo[d][1,3]oxazin-4-ones. The formation of the dihydro analogs correlated with the electron density on the aromatic ring: Electron-donating groups favored the 4H- benzo[d][1,3]oxazin-4-ones, while electron-withdrawing groups tended to favor the dihydro product. Substituting a pyridine ring for the benzene ring in the substrate acid suppressed the reaction.