This review deals with syntheses and reactions of pyrazines, especially, of 2, 5-disubstituted pyrazines. The description was made in due to order of 1) synthesis and properties of 2, 5-disubstituted pyrazines, 2) synthesis of 2, 5-disubstituted pyrazine N-oxides, 3) synthesis of pyrazinols, 4) synthesis and utilization of pyrazinethiols ; preparation of aldehydes, utilization as an acyl carrier, and preparation of olefins via the elimination of pyrazinylsulfinyl group, 5) synthesis of aminopyrazines, 6) synthesis of azidopyrazines and their transformation to imidazoles, 7) palladium-catalyzed reactions of chloropyrazines ; dechlorination, introduction of cyano, alkenyl, alkynyl, alkyl, and aryl groups to the pyrazine ring. The cross-coupling of chloropyrazines with aromatic heterocycles such as furan, thiophene, pyrroles, indoles, benzo [b] furan, benzo [b] thiophene, oxazole, thiazole, benz [b] oxazole, and benzo [b] thiazole is also described.
The electrical surface properties of biological cells have been studied, which provided us with the fundamental knowledge about the cell surface. The change in shape or biological functions of cells may affect the surface properties and can be detected by electrokinetic measurements. Biological cell surfaces are covered with polysaccharide chains, some are charged and some are not. Some polysaccharides produce a hydrogel matrixes under a proper condition. We thus consider it reasonable that cell surface is approximated by a hydrogel surface. Electrophoretic mobility measurements are useful for studying the surface properties of biological cells suspended as colloidal particles in an electrolyte solution. The electro-osmotic velocity measurements on the other hand are advantageous to the study of the surface properties of slab-shaped biological systems such as membranes. This work was started with a hydrogel, as a model material. As a hydrogel, poly (N-isopropylacrylamide) poly (NIPAAm), abbreviated as hereafter, was chosen, because this hydrogel changes its volume depending on temperature. The dependence of the electrophoretic mobility of latex particles covered with poly (NIPAAm) hydrogel layer or of the electro-osmotic mobility on poly (NIPAAm) plate upon temperature and ionic strength of the dispersing medium was well explained with an electrophoretic mobility formula for "soft particles" developed by Ohshima. The electrokinetic measurements and the explanation of data with an electrophoretic mobility formula for "soft particles " give usinformation about the surface charge density and the "softness" of soft surfaces. On the basis of the findings with hydrogels, we have discussed the relationship between the changes in shape or function of the biological cells and the change in physicochemical surface properties using these measurements. To study the change in physicochemical properties of the cell surface caused by apoptosis, we have measured the electrophoretic mobilities of intact and apoptotic human promyelocytic leukemia cell lines, HL-60RG cells. We have also studied the differences observed in surface properties of malignant lymphosarcoma cell line, RAW117-P, and its variant, RAW117-H10, with a high metastatic property to the liver. In both cases, the cell surfaces became softer by the changes of biological functions. We have applied electrophoresis and electro-osmosis measurements to the study of the electrokinetic surface properties of rat basophilic leukemia cells, RBL cells. It was also found that the surface of Human umbilical vein endothelial cells, HUVEC, is considerably soft as compared with those of other biological cells we have studied before.
This review chiefly describes the syntheses of naturally occurring hydroxypyrazines. First, typical hydroxamic acid type pyrazines such as aspergillic acid, neoasperegillic acid, pulcherriminic acid, and their derivatives are mentioned. Next, synthesis of arglecin and its derivatives, which are hydroxypyrazines carrying with guanidyl group on the side chain, via base-mediated elongation reaction of the carbon skeleton of the 2, 5-dialkylpyrazines are described. Third, synthesis and structural revision of emehetelone, a methoxy-hydroxypyrazine, are included. Septorine, an antibiotic agent from Streptomyces nodorum, is a methoxy-hydroxypyrazine carrying with an aroyl group on the pyrazine ring. The synthesis of septorine was accomplished by utilization of the selective PMA (permaleic acid) oxidation of the chloropyrazine. Further, OPC-15161 and astechrome, which are hydroxypyrazine and pyrazinyl hydroxamic acid, respectively, carrying pyrazine and indole rings, were prepared. Finally, syntheses of terramide A, B, and C, cyclic bishydroxamic acid type piperazines, via the reduction of 2, 5-dihydroxypyrazine 1, 4-dioxides are described.
In order to elucidate the morphological variation and the origin of erythrocytic micronuclei induced by mitotic inhibitors, each of clastogens (mitomycin C and cyclophosphamide) and spindle poisons (vincristine and colchicine) was administered intraperitoneally into a rat. After 24 h, the bone marrow smear was prepared and subjected to the microscopic analysis. In consequence, the sizes of micronuclei (MNSs) induced by spindle poisons were generally larger than those (MNCs) induced by clastogens. On the other hand, the bone marrow cells containing micronucleated erythrocytes were fractionated by cellulose column chromatography and then Percoll-gradient centrifugation. The micronuclear DNA was extracted from the resulting erythrocyte fraction and subjected to the dot blot hybridization with a centromeric or telomeric DNA probe. This experiment showed that centromeric and/or telomeric DNAs are enriched more in MNSs than in MNCs. Thus, such hybridization techniques and the morphological analysis would be available for classifying micronucleus-inducing drugs.
This investigation was carried out to try the application of pilocarpine hydrochloride (PC) solid dispersion as sustained release dosage form. Four preparations of PC with ethylcellulose and/or hydroxypropylmethylcellulose phthalate were prepared by the organic solvent method. The preparation D including PC : ethylcellulose : hydroxypropylmethylcellulose phthalate (1 : 9 : 10 at weight ratio) showed the best sustained release behavior in dissolution test among four preparations. The preparation D was examined by powder X-ray diffractometry and differential scanning calorimetry, and confirmed to be solid dispersion. Saliva secretory effect of preparation D was examined in healthy male volunteers, and its effect for Xerostomia was showed.