Bioavailable acyl-CoA: cholesterol acyltransferase inhibitor with anti-peroxidative activity: synthesis and biological activity of novel indolinyl amide and urea derivatives

We synthesized a series of indoline derivatives with an amide or urea moiety and examined their inhibitory effects on acyl-CoA:cholesterol acyltransferase (ACAT) activity, lipid-peroxidation and serum cholesterol levels in experimental animals. Among the derivatives synthesized, a series of N-(1-alkyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamides++ + potently inhibited rabbit intestinal ACAT activity and lipid-peroxidation of rat brain homogenate. The effect on ACAT activity was related to the length of the alkyl chain at the 1-position of indoline. N-(4,6-Dimethyl-1-octylindolindolin-7-yl)-2,2-dimethylpropanami de hydrochloride (55) showed inhibitory effects on intestinal and hepatic ACAT activity slightly weaker than those of YM-750, and an inhibitory effect on low density lipoprotein (LDL)-peroxidation similar to that of probucol. Compound 55 also reduced serum cholesterol at 10 mg/kg/d in hyperlipidemic rats and 20 mg/kg/d in normolipidemic hamsters. The plasma concentration of 55 reached 716 ng/ml in dogs (10 mg/kg, p.o.), which is an effective concentration against hepatic ACAT activity and LDL-peroxidation. In conclusion, compound 55 is a novel bioavailable ACAT inhibitor with anti-peroxidative activity and is thus a promising anti-atherosclerotic and anti-hyperlipidemic drug. Indoline proved to be a useful pharmacophore for molecular design of new anti-peroxidative drugs.     

Synthesis of 3-phenylpyrroles by hydride reduction of 4-hydroxypyrrolidin-2-ones

3-Phenylpyrroles 2 were easily prepared in good yields by hydride reduction of 4-hydroxypyrrolidin-2-ones 1 , which have been prepared in high yields from the photoreaction of N,N-dialkylbenzoylacetamides, with lithium aluminum hydride.     

Proton transfer and a dielectric phase transition in the molecular conductor (HDABCO+)2(TCNQ)3

One-dimensional dielectric (N.H.N)( infinity ) hydrogen-bonding chains of monoprotonated 1,4-diazabicyclo[2.2.2]octane (HDABCO(+)) were introduced into an electrically conducting 7,7,8,8-tetracyano-p-quinodimethane (TCNQ) salt as the countercation structure. Room-temperature electrical conductivity was approximately 10(-)(3) S cm(-)(1), with a semiconductive behavior. The temperature-dependent dielectric constants of (HDABCO(+))(2)(TCNQ)(3) indicated a dielectric transition at 306 K. A large deuterium isotope effect for the dielectric transition (DeltaT = 70 K) was observed for the deuterated salt, (DDABCO(+))(2)(TCNQ)(3). Thermally activated order/disorder of the protons or deuteriums within the one-dimensional hydrogen-bonding chains of (HDABCO(+))( infinity ) and (DDABCO(+))( infinity ) affected the dielectric responses in the TCNQ-based semiconductors.     

Processing of β-BaB2O4 Thin Films Through Metal Organics

β-BaB₂O₄ (β-BBO) thin films were successfully synthesized by the sol-gel method using metallo-organic compounds. A stable BBO precursor solution was prepared from barium metal and boron triethoxide or 2,4,6-triethoxycyclotriboroxane in a mixture solvent of ethanol and 2-ethoxyethanol. As-precipitated powder formed by hydrolysis of the precursor solutions crystallized to ψ phase, which was transformed to β phase at higher temperatures. The transformation temperatures of powders from ψ to β phase of the ethoxide system and the boroxane system were 600 and 680°C, respectively. The calcination of precursor films in a mixture gas of water and oxygen was found to decrease the crystallization temperature of β-BBO films on Pt sheet substrates. The precursor films prepared from the ethoxide system and the boroxane system crystallized to β-BBO on Pt (111)/glass substrates at 500 and 550°C, respectively. The BBO films on Pt(111)/glass substrates showed the strong (006) preferred orientation. The β-BBO films on Pt(111)/glass substrates showed the second harmonic generation (SHG) of the 532 nm light on irradiation with 1064 nm light. The SH power from the BBO films was correlated with the fundamental power through the square-law proportionality based on the theory. The SHG efficiency of the BBO films was dependent upon the film thickness.     

NAD(P)+-NAD(P)H model. 52. Reduction of olefins by hantzsch ester on silica gel

Olefinic double bonds in α,β-unsaturated carbonyl or nitro compounds are reduced chemoselectively by Hantzsch ester on silica gel in excellent yields.     

Biaryl synthesis from two different aryl halides with tri(2-furyl)germane

[reaction: see text] The coupling reaction of germanium compounds with aryl halides has been developed. The Pd(0)-catalyzed reaction of aryl halides with tri(2-furyl)germane provides aryltri(2-furyl)germanes in good yield. The cross-coupling reaction of aryltri(2-furyl)germanes with aryl halides is achieved. This allows facile synthesis of unsymmetrical biaryls from two different aryl halides.     

The interaction of oxygen with TiC(001): photoemission and first-principles studies

High-resolution photoemission and first-principles density-functional slab calculations were used to study the interaction of oxygen with a TiC(001) surface. Atomic oxygen is present on the TiC(001) substrate after small doses of O(2) at room temperature. A big positive shift (1.5-1.8 eV) was detected for the C 1s core level. These photoemission studies suggest the existence of strong O<-->C interactions. A phenomenon corroborated by the results of first-principles calculations, which show a CTiTi hollow as the most stable site for the adsorption of O. Ti and C atoms are involved in the adsorption and dissociation of the O(2) molecule. In general, the bond between O and the TiC(001) surface contains a large degree of ionic character. The carbide-->O charge transfer is substantial even at high coverages (>0.5 ML) of oxygen. At 500 K and large doses of O(2), oxidation of the carbide surface occurs with the removal of C and formation of titanium oxides. There is an activation barrier for the exchange of Ti-C and Ti-O bonds which is overcome only by the formation of C-C or C-O bonds on the surface. The mechanism for the removal of a C atom as CO gas involves a minimum of two O adatoms, and three O adatoms are required for the formation of CO(2) gas. Due to the high stability of TiC, an O adatom alone cannot induce the generation of a C vacancy in a flat TiC(001) surface.     

A convenient and practical procedure to derive correction factors to estimate atomic ratios by XPS

In quantitative XPS, the preparation of reference samples is difficult or impossible, and the correction factor method has been employed. Therefore, a convenient and practical procedure to get correction factors to estimate atomic ratios is proposed, in which it is assumed that the XPS intensity distribution corresponds to the distribution of the photoionization cross section. This procedure can be applied to some instruments and various samples without the previous collection, preparation of reference sample groups, and determination of sensitivity factors for each element.     

Preparation and characterization of fluorine-containing aromatic condensation polymers. II. Preparation and characterization of fluorine-containing aromatic polyformal and copolyformals by solution polycondensation of 2,2-bis (4-hydroxyphenyl)-1,1,1,3,3,3-hexafluoropropane and/or 2,2-bis-(4-hydroxyphenyl)propane with dichloromethane

A series of fluorine-containing aromatic homopolyformal and copolyformals with a wide range of unit ratio were synthesized by the solution polycondensation of 2,2-bis (4-hydroxyphenyl)-1,1,1,3,3,3-hexafluoropropane (Bisphenol AF) and/or 2,2-bis (4-hydroxyphenyl)propane (Bisphenol A) with dichloromethane, and the effect of the fluorine substitution on the preparation and properties of these polymers was investigated by comparing with those of Bisphenol-A-based homopolyformal without fluorine. Irrespective of the ratio of Bisphenol AF, high-molecular-weight, fluorine-containing polyformals with reduced viscosities of 1.4–5.3 dL/g were obtained in high yields by using dichloromethane as both comonomer and solvent, potassium hydroxide as a base, and N-methyl-2-pyrrolidone as a comedium at 75°C for 4 h. Their solubility increased markedly by the introduction of fluorine atom. Colorless, transparent, and tough films were cast from chloroform solution irrespective of fluorine content. These films had good mechanical properties comparable to that of Bisphenol-A-based homopolyformal. The contact angles by water were larger than 90°, regardless of their fluorine contents, at 25°C. The glass transition temperature and thermal stability increased monotonically with increasing fluorine content. © 1994 John Wiley & Sons, Inc.     

Third virial coefficient of polystyrene in benzene

Second virial coefficients A₂ and third virial coefficients A₃ for benzene solutions of ten polystyrene fractions ranging in weight-average molecular weight M_w from 10⁴ to 2 × 10⁷ at 25°C were determined by light scattering. The third coefficient is represented approximately by A₃ = 8.0 × 10^?6 M mol g^?3 cm⁶ for M_w above 10⁵. In this molecular weight region, the factor g defined by A₃/AM_w/ This trend of g is consistent with predictions of early two-parameter theories but not with those of renormalization group theories. In particular, quantitative agreement is observed between the present experiments (for M_w ? 2 × 10⁵) and the mean-field two-parameter theory of Stockmayer and Casassa.