Ethyl 2-(4-hydr­oxy-1-methyl-2-oxo-1,2-dihydro­quinolin-3-yl)acetate

In the title compound, C14H15NO4, the bicyclic fragment and the ester group form a dihedral angle of 86.7 (2)°. Inter­molecular O—H⋯O and C—H⋯O hydrogen bonding connects mol­ecules into a helix along the crystallographic b axis

2-Bromo­methyl-N-isopropyl-7,8-dimeth­oxy-1,2-dihydro-1,3-oxazolo[3,2-a]quinoline-4-carboxamide

In the title compound, C18H21BrN2O5, conjugation between the π-donating N—C—O fragment and the π-withdrawing carbonyl group results in considerable redistribution of the electron density within the dihydropyridinol ring. This effect is also promoted by the formation of an intra­molecular N—H⋯O hydrogen bond. The five-membered heterocycle is disordered over two envelope conformations in a 0.35:0.65 ratio

Analysis of carbohydrates content in the plant components of antidiabetic herbal mixture by GC-MS

Medicinal plants and their combinations due to the wide range of biologically active substances can influence on various links of the pathogenetic mechanism of development of diabetes mellitus and its complications. One of such combinations is an antidiabetic herbal mixture (Urticae folia, Rosae frucrus, Myrtilli folia, Menthae folia and Taraxaci radices) with established hypoglycemic, hypolipidemic, antioxidant, hepatoprotective, pancreatoprotective activity in previous pharmacological study in vivo. Thus, the aim of this study was to identify and establish the content of carbohydrates in free and bound form in the plant components of antidiabetic herbal mixture. The carbohydrates were separated by gas chromatography-mass spectrometry after conversion into volatile derivatives as aldononitrile acetate. The monomeric composition of polysaccharides was studied after their hydrolysis to form monosaccharides and polyalcohols. The results of the quantitative study showed that the predominant carbohydrate in free form was saccharose in Urticae folia, L-fructose in Myrtilli folia, Rosae frucrus, Taraxaci radices and Menthae folia, L-glucose in Rosae frucrus. Concerning the determination of monomers of polysaccharides after hydrolysis, L-glucose prevailed in all plant components of antidiabetic herbal mixture. The chromatographic study revealed a number of polyalcohols that are important for the treatment and prevention of progression of diabetes mellitus and its complications, namely, mannitol and myo-inositol

Analysis of amino acids content in the plant components of the antidiabetic herbal mixture by GC-MS

Medicinal plants and their combinations due to the wide range of biologically active substances can influence on various links of the pathogenetic mechanism of development of DM type 2 and its complications. One of such combinations is an antidiabetic herbal mixture (Urticae folia, Rosae fructus, Myrtilli folia, Menthae folia and Taraxaci radices) with established hypoglycaemic, hypolipidemic, antioxidant, hepatoprotective, pancreatoprotective activity in previous pharmacological studies in vivo and in vitro and defined phytochemical composition. Thus, the aim of this study was to identify and establish the content of amino acids in the plant components of antidiabetic herbal mixture. The amino acids were separated by GC-MS method with pre-column derivatization. The calibration curves of twenty CRS of amino acids were linear (R2 > 0.98) over the range of 1–100 µg/mL, the LODs and the LOQs were in the range of 0.01–0.07 µg/mL and 0.02–0.20 µg/mL, respectively. The results of analysis showed that the predominant essential amino acid was L-proline in Taraxaci radices, Urticae folia, Rosae fructus and Menthae folia, its total content was 101.46 mg/g, 25.31 mg/g, 23.04 mg/g and 19.30 mg/g, respectively. In addition, it was established total content of essential amino acid – L-leucine that can stimulate insulin secretion in β-cells of the pancreas. Its total content was 58.51 mg/g in Taraxaci radices, 9.58 mg/g in Myrtilli folia, 4.68 mg/g in Rosae fructus, 2.99 mg/g in Urticae folia and 0.79 mg/g in Menthae folia. Chromatographic examination also revealed L-phenylalanine, an essential amino acid important for antidiabetic therapy that can increase insulin secretion, stimulate proliferation and neogenesis of β-cells of the pancreas and reduce insulin resistance. Its total content was 13.42 mg/g in Myrtilli folia, 2.23 mg/g in Rosae fructus, 1.478 mg/g in Urticae folia, 1.46 mg/g in Taraxaci radices and 0.52 mg/g in Menthae folia. This phytochemical study shows, which plant material forms the amino acid composition and content in the finished herbal mixture and due to which biologically active substances the antidiabetic activity of this phytocomposition is manifested

N-Aryl-7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido-[3,2,1-ij]quinoline-6-carboxamides. The Synthesis and Effects on Urinary Output

Continuing a targeted search for new leading structures with diuretic action among tricyclic derivatives of hydroxyquinolines, which are of interest as potential inhibitors of aldosterone synthase, the synthesis of a series of the corresponding pyrido[3,2,1-ij]quinoline-6-carboxanilides was carried out by amidation of ethyl-7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxylate with aniline, aminophenols and O-alkylsubstituted analogs with high yields and purity. The optimal conditions of this reaction are proposed; they make it possible to prevent partial destruction of the original heterocyclic ester and thereby avoid formation of specific impurities of 7-hydroxy-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinolin-5-one. To confirm the structure of all substances obtained, elemental analysis, nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry were used. Moreover, the peculiarities of their 1H and 13C-NMR spectra, as well as their mass spectrometric behavior under conditions of electron impact ionization, were discussed. The effect of pyrido[3,2,1-ij]quinoline-6-carboxanilides on the urinary function of the kidneys was studied in white rats of both genders by the standard method of oral administration at a dose of 10 mg/kg. Testing was conducted in comparison with hydrochlorothiazide, as well as with structurally close pyrrolo[3,2,1-ij] quinoline-5-carboxanilides studied earlier with the same substituents in the anilide fragments. It was found that addition of one methylene unit to the heterocycle partially hydrogenated and annelated with the quinolone core has a positive impact on biological properties—most of the substances studied exhibit a statistically significant diuretic effect exceeding the activity of not only hydrochlorothiazide, in some cases, but also the action of the structural analogs. The important structural and biological regularities, which are common with pyrroloquinolines and introduced by a chemical modification, were revealed. The importance of the presence in the structure of terminal amide fragments of tricyclic quinoline-3-carboxamides of a 4-methoxy-substituted aromatic ring was particularly marked. The expediency of further study of pyridoquinolines as promising diuretic agents has been shown

Methyl 4-Hydroxy-2,2-Dioxo-1H-2λ6,1-Benzothiazine-3-Carboxylate and Its Analogs Modified in the Benzene Moiety of the Molecule as New Analgesics

In order to identify new regularities of the “structure–analgesic activity” relationship in the series of 2,1-benzothiazine derivatives, the synthesis of methyl 4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate and a group of its analogs substituted in the benzene moiety of the molecule, as well as their mono-and diammonium salts, was performed with tris(hydroxymethyl)aminomethane. The algorithm was proposed; it allows for uniquely solving the question of the nature of the substituent and its true position in the benzothiazine core based on the complex use of NMR (1H and 13C) and mass spectrometry data. Using single-crystal X-ray diffraction analysis it was proven that salt formation first passes through the cyclic sulfamide group and only then through the 4-hydroxyl group, and is always accompanied by a significant conformational rearrangement of the molecule. Based on the results of pharmacological tests it was found that modification of the benzene moiety of the molecule can be used as a method for enhancing the analgesic properties of the class of compounds studied. The presence of a substitute in position 7 is particularly effective, regardless of its nature. A comparative analysis of the analgesic activity of the initial esters and their mono- and diammonium salts convincingly showed that the common belief about a direct relationship between the solubility of a substance and the level of its biological effect is not always true. As it turned out, increasing the solubility in water can lead to a variety of consequences: From a significant increase in analgesia to its complete elimination. It was suggested that the analgesic activity of the compounds studied is determined not by solubility, but by the molecular conformations formed during their obtainment