Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as factor Xa inhibitor

Intravascular clot formation is an important factor in a number of cardiovascular diseases. Therefore, the prevention of blood coagulation has become a major target for new therapeutic agents. One attractive approach is the inhibition of factor Xa (FXa), which is a key enzyme in coagulation cascade responsible for the generation of thrombin by limited proteolysis of its zymogen, prothrombin. We have investigated 1-arylsulfonyl-3-piperazinone derivatives, containing a 4-(piperidino)pyridine group in place of guanidino and/or amidino groups, and discovered compound M55113 (30a: 4-[(6-Chloro-2-naphthalenyl)sulfonyl]-1-[[1-(4-pyridinyl)-4-piperidinyl]methyl]piperazinone), as a potent inhibitor of FXa (IC50=0.06 microM) with high selectivity for FXa over trypsin and thrombin.     

Automated separation and measurement of radioxenon for the Comprehensive Test Ban Treaty

A fully automatic radioxenon sampler/analyzer (ARSA) has been developed and demonstrated for the collection and quantitative measurement of the four xenon radionuclides,^131mXe(11.9 d),^133mXe(2.2 d),¹³³Xe(5.2 d), and¹³⁵Xe(9.1 hr), in the atmosphere. These radionuclides are important signatures in monitoring for compliance to a Comprehensive Test Ban Treaty (CTBT). Activity ratios of these radionuclides permit source attribution. Xenon, continuously and automatically separated from the atmosphere, is automatically analyzed by electron-photon coincidence spectrometry providing a lower limit of detection of about 100 μBq/m³. The demonstrated detection limit is about 100 times better than achievable with reported laboratory-based procedures for the short-time collection intervals of interest.     

Collaborative monitoring study of airborne particulate matters among seven Asian countries

Summary Seven Asian countries have been collaborating in collecting airborne particulate matter (APM) in their individual countries and analyzing them by neutron activation analysis as a common analytical tool. APM samples were collected into two fractions of fine and coarse grains (PM2 and PM2-10, respectively). Analytical data were compared from several viewpoints such as particulate sizes, locality of sampling sites (either urban or rural) and geographical location of participating countries. Chemical composition and their monthly variations as well as mass concentrations appear to be highly characteristic for individual sampling sites, suggesting that NAA data are suitable for evaluating the air quality in each site.     

Anodic layers formed in polyphosphate electrolytes on rectifying metals

Results obtained in studying the elemental and phase composition of anodic layers formed on titanium, aluminum, niobium, and zirconium under the action of electric discharges in aqueous electrolytes with hexametaphosphate complexes of Ni(II), Mg(II), and Mn(II) are presented.     

Synthesis,electronic structure,and physicochemical characteristics of pyrazolo[1,2-a]pyridazinium

The interaction of 1-methallylpyrazoles with acetic or propionic anhydride in the presence of perchloric acid forms products of acylation at the double bond and subsequent heterocyclization — pyrazolo[1,2-a]pyridazinium salts — that are representatives of a new heteroaromatic system. Analogous cyclization is observed in the acylation of 3-(2-hydroxy-2-methylpropyl-pyrazole.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1623–1631, December, 1990.     

Patents and literature

Protein engineering and site-directed mutagenesis is becoming immensely important in both fundamental studies and commercial applications involving proteins and enzymes in biocatalysis. Protein engineering has become a powerful tool to help biochemists and molecular enzymologists elucidate structure-function relationships in enzymic active sites, to understand the intricacies of protein folding and denaturation, and to alter the selectivity of enzymatic catalysis. Commercial applications of engineered enzymes are being developed to increase protein stability, widen or narrow substrate specificity, and to develop novel approaches for use of enzymes in organic synthesis, drug design, and clinical applications. In addition to protein engineering, novel expression systems have been designed to prepare large quantities of genetically engineered proteins. Recent US patents and scientific literature on protein engineering, site-directed mutagenesis, and protein expression systems related to protein engineering are surveyed. Patent abstracts are summarized individually and a list of literature references are given.     

Development of a novel laboratory scale high solids reactor for anaerobic digestion of processed municipal solid wastes for the production of methane

Economic evaluations of the capital costs for anaerobic digestion systems for gas production show that the reactor is a significant cost component. The successful application of high solids digestion of processed MSW (e.g., greater than 10% solids within the digester) would allow a decrease in reactor volume with maintenance of relatively high gas production rates. However, high solids slurries do not mix well in conventional stirred tank reactors. A horizontal shaft, hydraulically driven reactor was designed and fabricated to test the anaerobic digestion of high solids concentrations. Digester performance was evaluated as a function of experimental parameters such as nutrient requirements, feeding rates, pH control, and agitator design/ rotation speed; horsepower of mixing was also evaluated for the reactor. Several startup protocols were examined to obtain a biologically stable anaerobic fermentation at high solids levels.     

Esr and polarography of nitroazoles. 4. Polarographic study of nitrobenzimidazoles

The electrochemical reduction of 2-substituted 5(6)-benzimidazoles has been studied with the aid of classical polarography and cyclic voltammetry in acetonitrile. The influence of the substituents in position 2 on the magnitudes of the half-wave potentials of the first stage is exerted by induction and resonance mechanisms with approximately the same contributions, and that on the magnitudes of the half-wave potentials of the second stage predominantly by the resonance mechanism. The possibilities of taking the radical-stabilizing factor into account in the correlations are discussed. In order to study the 2-substituted 5(6)-nitrobenzimidazole series, their pK _a values in acetonitrile have been determined by potentiometric titration.For communication 3, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1246–1251, September, 1984.