Thiazolium-Substituted Gem-Bisphosphonates

Abstract

Heterocyclic derivatives of gem-bisphosphonates exhibit various biological activities. We have found that thiazolium substituted bisphosphonic acids can be obtained by two-step synthesis from amino-bisphosphonates (I). Reaction of (I) with isothiocyanates in alkohol in the presence of triethylamine led to corresponding thioureas (II) obtained as natrium or triethylamonium salts [1]. Further treatment of (II) with α-bromoketones give aminothiazoles (III) with a good yield. As a rule only less hindered nitrogen atom is involved into the cyclization with formation of one from two of possible isomers.     

The Reactivity of Associates of Aminomethylated Calix [4] Resorcinolarenes towards P-Nitrophenyl Esters of Phosphorus Acids

Abstract

The kinetics of reactions of aminoinethylated calixarenes (AMC) of different structure (substituents at nitrogen atom as well as on the “lower” rim of cavity are varied) with esters of phosphorus acids has been studied under pseudofirst order conditions in water-DMF and water-alcohol (i-PrOH) solutions by spectrophotometry. The dependences of the observed rate constants of the reactions on the concentrations of AMC reach a plateaus at the investigated values of pH 8 - 1 1. This indicates binding of the substrates by the aggregates of AMC and allows to calculate the parameters of the reactions: CCA, k_a, K_b. It was shown by NMR ³¹P method, that AMC are the catalysts of hydrolysis of esters of phosphorus acids in water-DMF solutions. The higher reactivity of AMC as compared with the one of calix[4]resorcinolarenes and o-aminomethylphenols was found. It was revealed AMC preceeds in both media, however the reactivity of the aggregates is considerably less in the water - alcohol solutions than those in the water - DMF solutions.     

Biochemical and Structural Studies of Conserved Maf Proteins Revealed Nucleotide Pyrophosphatases with a Preference for Modified Nucleotides

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Development of Novel Stability-Indicating Method for the Determination of Dimethindene Maleate and Its Impurities

A novel and selective stability-indicating liquid chromatographic method has been developed and validated for the analysis of dimethindene maleate, the related substance 2-ethylpyridine, and three degradation products. Dimethindene maleate was subjected to forced degradation study by acid and basic hydrolysis, oxidation, and thermal decomposition. Three degradation products that were formed during the forced degradation study were separated from dimethindene using a Zorbax SB CN column (150 × 4.6 mm; 5 μm); cyanopropyl-bonded stationary phase was applied for the first time for the separation of dimethindene and its impurities. The proposed method was validated and was found suitable for quality control and stability tests of pharmaceuticals containing dimethindene maleate.

     

Reactions of 2- and 4-pyrones with secondary phosphine chalcogenides: a facile synthesis of functional phosphorylated pyrones

The oxidative cross-coupling between 4-hydroxy-6-methyl-2-pyrone or 3-hydroxy-2-methyl-4-pyrone and secondary phosphine chalcogenides proceeds in CCl₄/Et₃N under mild conditions (20–52 °С, 0.75–10 h) through the hydroxyl group to give O-(6-methyl-2-oxo-2H-pyran-4-yl) diorganylphosphinochalcogenoates or O-(2-methyl-4-oxo-4H-pyran-3-yl) diorganylphosphinochalcogenoates, in high yields.     

Regioselective synthesis of 2-unsubstituted 1-aryl-4- and 1-aryl-5-acylimidazoles

An efficient and simple method for the synthesis of 2-unsubstituted 1-aryl-4- and 1-aryl-5-acylimidazoles has been developed. It consists in the condensation of α-diketone monooximes with aromatic amines and formaldehyde on the presence of boron trifluoride etherate, leading to the formation of stable boron trifluoride complexes of N-oxides. Further reduction of these complexes led to the corresponding imidazoles. This method permits broad variations of substituents in the aryl part of these compounds.     

Characterization of hydromedusan Ca2+-regulated photoproteins as a tool for measurement of Ca2+concentration

Calcium ion is a ubiquitous intracellular messenger, performing this function in many eukaryotic cells. To understand calcium regulation mechanisms and how disturbances of these mechanisms are associated with disease states, it is necessary to measure calcium inside cells. Ca²⁺-regulated photoproteins have been successfully used for this purpose for many years. Here we report the results of comparative studies on the properties of recombinant aequorin from Aequorea victoria, recombinant obelins from Obelia geniculata and Obelia longissima, recombinant mitrocomin from Mitrocoma cellularia, and recombinant clytin from Clytia gregaria as intracellular calcium indicators in a set of identical in vitro and in vivo experiments. Although photoproteins reveal a high degree of identity of amino acid sequences and spatial structures, and, apparently, have a common mechanism for the bioluminescence reaction, they were found to differ in the Ca²⁺ concentration detection limit, the sensitivity of bioluminescence to Mg²⁺, and the rates of the rise of the luminescence signal with a sudden change of Ca²⁺ concentration. In addition, the bioluminescence activities of Chinese hamster ovary cells expressing wild-type photoproteins also differed. The light signals of cells expressing mitrocomin, for example, slightly exceeded the background, suggesting that mitrocomin may be hardly used to detect intracellular Ca²⁺ without modifications improving its properties. On the basis of experiments on the activation of endogenous P2Y₂ receptor in Chinese hamster ovary cells by ATP, we suggest that wild-type aequorin and obelin from O. longissima are more suitable for calcium detection in cytoplasm, whereas clytin and obelin from O. geniculata can be used for calcium measurement in cell compartments with high Ca²⁺ concentration. Figure

Hydromedusan photoproteins differ in Ca²⁺ concentration detection limit, sensitivity of bioluminescence to Mg²⁺, and rates of rise of luminescence signal with a sudden change of [Ca²⁺] despite a high degree of identity of their amino acid sequences and spatial structures, and, apparently, a common mechanism for the bioluminescence reaction.     

Elemental Sulfur Disproportionation in the Redox Condensation Reaction between o‐Halonitrobenzenes and Benzylamines

The disproportionation of elemental sulfur at moderate temperatures is investigated in the redox condensation involving o‐halonitrobenzenes 1 and benzylamines 2 . As a redox moderator, elemental sulfur plays the dual role of both electron donor and acceptor, generating its lowest and highest oxidation states: S^?2 (sulfide equivalent) in benzothiazole 3 and S⁺⁶ (sulfate equivalent) in sulfamate 4 , and filling the electron gap of the global redox condensation process. Along with this process, a cascade of reactions of reduction of the nitro group of 1 , oxidation of the aminomethyl group of 2 , metal‐free aromatic halogen substitution, and condensation finally led to 2‐arylbenzothiazoles 3 .     

Fast choice of separation conditions for analyses by capillary zone electrophoresis using an information system Xemic

An information system Xemic applicable in analytical chemistry is described and its use in capillary electrophoresis for searching suitable separation conditions is demonstrated. This system is capable to provide suitable separation conditions even for analytes for which no electrophoretic experiments have been published so far. The system works with a database of components of anionic character the analyses of which have been performed, published in reviewed scientific journals, and included into a database created by an expert. Moreover, the system learned to search also in abstracts or complete scientific articles to find articles dealing with the determination of a substance in a given sample matrix. When no experiments have been published so far for a defined substance in a specific matrix, Xemic shows the separation conditions for determination of the substance regardless of the matrix. When no response can be found for the analyte of interest at all, the system Xemic works like an expert in the field and searches chemically similar substances and offers a series of substances the physicochemical properties of which are close to the followed analyte with respect to the behavior in the electric field, and shows working conditions for their analysis. Thus, the analyst puts only the order in the form of a given analyte in a given matrix and obtains a recommendation of a separation system that should enable to perform a successful separation. The system is not rigid and enables the operator to change the importance of individual attributes used in similarity search so as to obtain a broader or narrower group of similar components. With a certain probability the analyte of interest can be successfully analyzed under separation conditions that suited for the analysis of the most similar substances in the given matrix.