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Crystal structure and structural disorder of Ba3MgSi2O8were reinvestigated by laboratory X-ray powder diffraction. The title compound was found to be trigonal with space groupP3m1,Z=1, and unit-cell dimensionsa=0.561 453(4) nm,c=0.727 629(4) nm, andV=0.198 641(2) nm3. The initial structural model used for structure refinement was taken from that of glaserite (K3NaS2O8) and modified by a split-atom model. In the split-atom model, one of the two types of Ba sites and that of SiO4tetrahedra were, respectively, positionally and orientationally disordered. The new crystal structure and structural disorder were refined by the Rietveld method. The maximum-entropy-method-based pattern fitting (MPF) method was used to confirm the validity of the split-atom model, in which conventional structure bias caused by assuming intensity partitioning was minimized. The final reliability indices calculated from MPF wereRwp=6.52%,S=1.36,Rp=4.84%,RB=0.97%, andRF=0.52%. Details of the disorder structure of Ba3MgSi2O8are shown in the three-dimensional and two-dimensional electron-density distribution maps determined by MPF.

For forty-three clinical test values presumably associated to common complex human diseases, we carried out a genome-wide association study using 600K SNPs in a general Japanese population of 1,639 individuals (1,252 after quality control procedures) drawn from a regional cohort, followed by a replication study for statistically significant SNPs (p = 1.95 × 10(-9)-8.34 × 10(-39)) using an independent population of 1,671 from another cohort. In this single two-stage study, we newly found strong and robust associations of common variants at the ABO histo-blood glycosyltransferase locus in 9q32 with the plasma levels of pancreatic lipase (P-LIP), in addition to successful confirmation of the known ABO association of angiotensin converting enzyme (ACE) independent of the ACE1 gene in 17q23.2 with the ACE level. Our results are compatible with the previously reported association between the ABO gene and pancreatic cancer, and show that the effect of these common variants at the ABO locus on the P-LIP and ACE levels is largely opposing and pleiotropic.

The effects of human urotensin II on coronary flow were studied in the perfused rat heart. Urotensin II transiently decreased coronary flow, then induced sustained vasodilatation. In the presence of a cyclooxygenase inhibitor, diclofenac, coronary vasodilatation was significantly inhibited. A nitric oxide synthase inhibitor, N G -nitro- l -arginine ( l -NNA), attenuated the urotensin-induced vasodilatation. These data suggest that urotensin II modulates coronary flow through factors such as cyclooxygenase products and nitric oxide to elicit coronary vasodilatation.

In order to find antimicrobial agents, compounds of 6-substituted 3-(p-nitrophenylsulfonamido) pyridazine, 6-substituted 3-(p-tolylsulfonamido) pyridazine and 6-substituted 3-(p-aminomethylphenylsulfonamido) pyridazine were synthesized and screened as to their activities on Staph. aureus and E. coli, but any of them was found uneffective.

For the purpose of industrial application, some new synthetic methods of 3-sulfanilyl-6-alkoxypyridazine were examined and the reaction of 3-(p-acetamidophenylsulfonamido)-6-chloropyridazine with sodium alkoxide in the corresponding alcohol was found to produce 3-sulfanilyl-6-alkoxypyridazine and the corresponding alkyl ester of acetic acid in both excellent yields. To investigate the mechanisms of this reaction, 3-(p-acetamidophenylsulfonamido)-6-chloropyridazine, 3-(p-acetamidophenylsulfonamido)-6-methoxypyridazine and 3-sulfanilyl-6-chloropyridazine were reacted with sodium methoxide in methanol under various conditions, and estimated the percentages of deacetylation and methoxylation by determining the amount of ester and sodium acetate and chlorine ion. From these results, it was found that the deacetylation and the methoxylation proceeded simultaneously in this reaction of two points, and the objective compound 3-sulfanilyl-6-methoxypyridazine was produced in a good yield. Thus, this method was found available for the industrial production of 3-sulfanilyl-6-methoxypyridazine.

In order to find antimicrobial agents, the substitution of 3-acetamido-6-alkoxypyridazine 2-oxide was investigated. As the results obtained, it was made clear that a number of 3-acetamido-6-alkoxypyridazine, 3-amino-6-alkoxypyridazine and their 2-oxides having such a substituent group as nitro, amino, hydroxyamino, azo, hydrazo, chloro, methoxy, methylthio, hydroxy, and mercapto at 5-position of the pyridazine rings, were synthesized. This finding is of use to develope the chemistry of pyridazine. Among these new compounds, 3-acetamido-and 3-amino-5-nitro-6-alkoxypyridazine 2-oxides were found to exert excellent in vitro effects on pathogenic bacteria.

To find more improved sulfonamide drugs, 3-sulfanilyl-6-hydroxy-, 3-sulfanilyl-6-mercapto-, 3-sulfanilyl-6-alkoxy-and 3-sulfanilyl-6-alkylthio-pyridazine and their intermediates, 3-amino-6-hydroxy-, 3-amino-6-mercapto-, 3-amino-6-alkoxy- and 3-amino-6-alkylthio-pyridazine were synthesized. Few synthetic procedures via different routes were examined as to the synthesises of 3-sulfanilyl-6-alkoxy-, 3-sulfanilyl-6-alkylthio-and 3-amino-6-methoxy-pyridazine.Activities of the compounds of 6-substituted-3-sulfanilyl-pyridazine on some kinds of bacteria and viruses were examined and among thern, 3-sulfanilyl-6-methoxy-, 3-sulfanilyl-6-ethoxy and 3-sulfanilyl-6-methylthiopyridazine were found to exert remarkableantibacterial effects.

It was found that N-oxidation of 3-acetamidopyridazine gave a mixture of 1-oxide and 2-oxide and the 2-oxide had a tautomeric N-acetoxy from, while N-oxidation of 3-acetamido-6-methoxypyridazine, 3-amino-6-methoxypyridazine and 3-amino-6-chloropyridazine afforded exclusively 2-oxide.