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Ogino M Nakada Y Negoro N Itokawa S Nishimura S Sanada T Satomi T Kita S Kubo K Marui S 《Chemical & pharmaceutical bulletin》2011,59(11):1369-1375
As a part of our research for novel potent and orally available acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors that can be used as anti-atherosclerotic agents, we recently reported the discovery of the (4-phenylcoumarine)acetanilide derivative 1. However, compound 1 showed adrenal toxicity in animal models. In order to search for safer ACAT inhibitors that do not have adrenal toxicity, we examined the inhibitory activity of ACAT in human macrophage and adrenal cells. The introduction of a carboxylic acid moiety on the pendant phenyl ring and the adjustment of the lipophilicity led to the discovery of (2E)-3-[7-chloro-3-[2-[[4-fluoro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl]-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]acrylic acid (21e), which showed potent ACAT inhibitory activity in macrophages and a selectivity of around 30-fold over adrenal cells. In addition, compound 21e showed high adrenal safety in guinea pigs. 相似文献
104.
Masanori Miura Takanori Koike Tsukasa Ishihara Shuichi Sakamoto Minoru Okada Mitsuaki Ohta 《合成通讯》2013,43(5):667-674
A one‐pot synthetic method of unsymmetrical biaryls was developed via the Suzuki cross‐coupling reaction of aryl halide using a phase‐transfer catalyst in a biphasic solvent system. 相似文献
105.
Geometriae Dedicata - In the theory of cluster algebras, a mutation loop induces discrete dynamical systems via its actions on the cluster $${\mathcal {A}}$$ - and $${\mathcal {X}}$$ -varieties. In... 相似文献
106.
Suzuki K Matsuo T Hashizume D Tamao K 《Journal of the American Chemical Society》2011,133(49):19710-19713
A room-temperature dynamic equilibrium between dibromodisilenes and bromosilylenes has been demonstrated by taking advantage of the steric protection using the fused-ring bulky 1,1,3,3,5,5,7,7-octa-R-s-hydrindacen-4-yl (Rind) groups. Although the bromosilylenes cannot be directly observed by spectroscopic methods, the thermal homolytic cleavage of the Si═Si double bond has been confirmed by a pseudo-first-order kinetics for the trapping with bis(trimethylsilyl)acetylene and a crossover reaction using two kinds of Rind-substituted dibromodisilenes. The addition of 4-pyrrolidinopyridine (PPy) to the dibromodisilene leads to an equilibrium mixture between the dibromodisilene and a PPy adduct of bromosilylene, the latter being isolated and characterized. The substitution of the bromine atom in the dibromodisilene by the Grignard reagent is significantly accelerated by the addition of PPy. 相似文献
107.
Shoji Y Matsuo T Hashizume D Gutmann MJ Fueno H Tanaka K Tamao K 《Journal of the American Chemical Society》2011,133(29):11058-11061
Diborane(6) as a H-bridged dimer of monoborane can be converted cleanly by two-electron reduction into diborane(6) dianion, which is isoelectronic with ethane, through B-B σ-bond formation when each boron atom has a bulky ligand on it. The existence of the B-B σ bond is supported by the X-ray molecular structure [B-B bond length of 1.924(3) ?], NMR studies, magnetic susceptibility measurements, and DFT calculations. Stepwise hydride abstraction reactions of the diborane(6) dianion produce the corresponding H-bridged diborane(5) anion and doubly H-bridged diborane(4) without B-B bond scission. 相似文献
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Tsukasa Nakayama 《国际流体数值方法杂志》1990,10(6):683-695
A new numerical method has been developed for the analysis of unsteady free surface flow problems. The problem under consideration is formulated mathematically as a two-dimensional non-linear initial boundary value problem with unknown quantities of a velocity potential and a free surface profile. The basic equations are discretized spacewise with a boundary element method and timewise with a truncated forward-time Taylor series. The key feature of the present paper lies in the method used to compute the time derivatives of the unknown quantities in the Taylor series. The use of the Taylor series expansion has enabled us to employ a variable time-stepping method. The size of time increment is determined at each time step so that the remainders of the truncated Taylor series should be equal to a given small error limit. Such a variable time-stepping technique has made a great contribution to numerically stable computations. A wave-making problem in a two-dimensional rectangular water tank has been analysed. The computational accuracy has been verified by comparing the present numerical results with available experimental data. Good agreement is obtained. 相似文献
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