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61.
Watanuki S Matsuura K Tomura Y Okada M Okazaki T Ohta M Tsukamoto S 《Chemical & pharmaceutical bulletin》2011,59(8):1029-1037
A series of 1-isopropyl-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized and their bradycardic activities were evaluated in isolated guinea pig right atria. Structure-activity relationship studies revealed that the introduction of an appropriate substituent and its position on the 1,2,3,4-tetrahydroisoquinoline ring are essential for potent in vitro activity. Furthermore, the tether between the piperidyl moiety and the terminal aromatic ring is important for potent antihypertensive activity. Oral administration of 6-fluoro-1-isopropyl-2-{[1-(2-phenylethyl)piperidin-4-yl]carbonyl}-1,2,3,4-tetrahydroisoquinoline (3b) to spontaneously hypertensive rats (SHR) elicited antihypertensive effects without inducing reflex tachycardia, which is often caused by traditional L-type Ca2? channel blockers. 相似文献
62.
Watanuki S Matsuura K Tomura Y Okada M Okazaki T Ohta M Tsukamoto S 《Chemical & pharmaceutical bulletin》2011,59(11):1376-1385
We synthesized and evaluated inhibitory activity against T-type Ca(2+) channels for a series of 1-alkyl-N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]piperidine-4-carboxamide derivatives. Structure-activity relationship studies have revealed that the isopropyl substituent at the benzylic position plays an important role in exerting potent inhibitory activity, and the absolute configuration of the benzylic position was found to be opposite that of mibefradil, which was first launched as a new class of T-type Ca(2+) channel blocker. Oral administration of N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]-1-[2-(3-methoxyphenyl)ethyl]piperidine-4-carboxamide (17f) lowered blood pressure in spontaneously hypertensive rats without inducing reflex tachycardia, an adverse effect often caused by traditional L-type Ca(2+) channel blockers. 相似文献
63.
Kawai Y Tsukamoto S Ito J Akimoto K Takahashi M 《Chemical & pharmaceutical bulletin》2011,59(9):1110-1116
The blockade of human ether-a-go-go-related gene (hERG) potassium channels is widely regarded as the predominant cause of drug-induced QT prolongation. The correlation analysis between the inhibition of the hERG channel (hERG inhibition) and physicochemical properties was investigated by use of in-house quinolone antibiotics as model compounds. In order to establish a simple prediction model of hERG inhibition, we focused on the comprehensible physicochemical parameters such as lipophilicity (log P) and basicity (pK(a)). At first, the risk associated with increasing log P and pK(a) was examined by statistical analysis. It was demonstrated that the risk associated with increasing log P and pK(a) by one unit, respectively, almost identically increased. Consequently, equal attention should be paid to both parameters on hERG inhibition. Next, a prediction model of hERG inhibition which was represented by log P and pK(a) was investigated. As a result, we built the stepwise discriminant prediction model which took advantage of the risk judgment by zone classification. In conclusion, the impact of log P and pK(a) on hERG inhibition was clarified relatively and quantitatively. The quantitative risk assessment established based on both parameters, was considered to be a practical and useful tool in avoiding hERG inhibition and in the rational drug design for drug discovery, especially in lead optimization. Moreover, we also carried out a trend analysis using a different derivative and demonstrated that both parameters were equally significant for hERG inhibition. 相似文献
64.
Tsukamoto K Shinohara Y Iwasaki S Maeda H 《Chemical communications (Cambridge, England)》2011,47(17):5073-5075
For detection of Hg(2+) and Ag(+), we have developed a coumarin-based probe with an N'-acetylthioureido group as a novel fluorescence switch, in which the hydrogen bond formation between the N-hydrogen and the acetyl O atom markedly increases the susceptibility of the probe toward desulfurization by Hg(2+) and Ag(+). 相似文献
65.
Fukaya Y Tsukamoto A Kuroda K Ohno H 《Chemical communications (Cambridge, England)》2011,47(7):1994-1996
We firstly developed high performance liquid chromatography methods with "ionic liquids" as eluents (HPILC) and successfully demonstrated the analysis of various biopolymers including scarcely soluble highly polymerized cellulose by means of HPILC with highly polar ionic liquid. 相似文献
66.
This paper investigates the flow field near three intersecting shock waves appearing in steady Mach reflection. Results of
numerical computations reveal a “von Neumann Paradox”—like feature for weak shock waves, in which the flow field between the
reflected and the Mach stem is smooth with no distinct slip flow region and changes rather smoothly. An analytical solution
of the Navier–Stokes equations constructed using a polar–coordinate system gives a flow field with the same properties as
the numerical simulation. 相似文献
67.
O. Tsukamoto S. Ishii Y. Kito S. Fukui H. Mukai J. Fujikami K. Hayashi K. Sato 《Physica C: Superconductivity and its Applications》1998,310(1-4):197-201
We study experimentally and theoretically the AC transport current loss characteristics of a tape in multiple tapes assembled in single layer and subject to external field produced by transport currents of adjacent tapes. We measured the AC transport current losses of a Bi2223 silver-sheathed tape in a single layer arrangement of three tapes using our newly developed potential leads arrangement to avoid spurious loss components caused by the magnetization in the adjacent tapes. In the paper, the influence of the external AC field produced by adjacent tapes on the loss characteristics is studied based on the experimental results and theoretical analysis. 相似文献
68.
69.
Sorption and diffusion of Sr were examined using a typical Japanese bentonite. The experimental results showed that Sr sorption
on the bentonite had linear relationship between the equilibrium Sr concentration and Sr sorption amount, i.e., Henry’s type
of sorption, in wide initial Sr concentration from 1.1×10−9 to 1.1×10−4 mol L−1 at pH 10. The Sr sorption also indicated pH dependence in pH range between 2 and 12. Sorption modelling calculation indicated
that cation-exchange reactions contributed to Sr sorption in the pH range studied and a surface complexation reaction was
predominant above pH 8. Diffusion of Sr in loosely compacted bentonite bed was described by pore and surface diffusion and
surface complexation of Sr. Chemical-transport calculations reproduce the diffusion data at pH 5 using the cation-exchange
parameters obtained in the analysis of the batch sorption experiment. 相似文献
70.
Sachiko Ohtani 《Journal of Number Theory》2006,120(2):272-286
We study the deformation theory of Galois representations whose restriction to every decomposition subgroup is abelian. As an application, we construct unramified non-solvable extensions over the field obtained by adjoining all p-power roots of unity to the field of rational numbers. 相似文献