Conformations and steric and stacking interactions of trisubstituted ureas and thioureas with alkyl and phenyl groups

The monomeric ν(N—H) vibrations of various trisubstituted ureas of the R₂UPh type and -thioureas of the R₂TUPh type have been studied. The trans—out isomerism in the former and the trans—out—cis isomerism in the latter are discussed from the point of view of steric effect. The monomeric ν(N—H) vibrations of RPhUPh and RPhTUPh are also examined. The single band appearing in the spectrum of both ureas is characteristic of the cis form; this suggests the existence of phenyl—phenyl interaction (the stacking interaction proposed by Galabov et al. [10]). Behavior of ν(N—H) vibrations at several concentrations is shown to be clearly different in the three forms (trans, out and cis). The presence of the cis form is confirmed by solvent effect experiments.     

Neutron activation analysis of low level lithium in water samples

For determining low level lithium concentrations in water, a neutron activation method based on the measurement of tritium radioactivity produced by⁶Li(n,)³H reaction has been developed. This method is specific and free from interference by other chemical elements. Using a low background liquid scintillation counter for tritium measurement, the detection limit is approximately 0.3 ppm during irradiation at a thermal neutron flux density of 1.1·10⁷n·cm^–2·s^–1 for 6 hours by a small nuclear reactor and liquid scintillation counting for 2000 minutes     

New hydroxyl protecting groups of a safety-catch type removable by reductive acidolysis.

New hydroxyl protecting groups of a safety-catch type, i.e., 4-methylsulfinylbenzyl-oxycarbonyl (Msz) group for Tyr and 4-methylsulfinylbenzyl (Msob) ether for Thr, have been developed. O-Msz and O-Msob groups are stable under both acidic and basic conditions and can be removed by a one-pot reaction involving reductive acidolysis using tetrachlorosilane-trifluoroacetic acid (TFA)-scavengers. Using these new protecting groups, a 17 residue-peptide, gamma-endorphin, was successfully synthesized by the efficient solid phase method.     

Preparation of prolonged-release spherical micro-matrix of ibuprofen with acrylic polymer by the emulsion-solvent diffusion method for improving bioavailability

Prolonged-release spherical micro-matrices of ibuprofen with acrylic polymer (Eudragit RS) were prepared using a novel emulsion-solvent diffusion method. It was found by examining cross sections of the spherical matrix before and after dissolution tests with a scanning electron microscope and a porosimeter that the resultant micro-matrix had a sponge-like internal structure. The spherical matrices were successfully recovered with a relatively high concentration of the drug in ethanol (0.4-0.6 g/ml) and over a wide range of temperatures (5-35 degrees C). The size of the spherical matrix could be easily controlled by varying the agitation speed of the system and the concentration of emulsifier added to the aqueous medium. The drug release rate from the spherical matrix decreased with increasing concentration of polymer formulated due to the reduced diffusion path and increased tortuosity in the matrix. Spherical matrices with ibuprofen:Eudragit RS = 3:1 improved the bioavailability of the drug and prolonged the drug action in beagle dogs.     

Steady-state and nanosecond spectroscopic studies of triplet sensitized reaction of K-region arene oxides

Photorearrangement reactions of K-region arene oxides, 9,10-epoxy-9,10-dihydrophenanthrene (1a), 3-acetyl-9,10-epoxy-9,10-dihydrophenanthrene (1b), and 3,4-epoxy-3,4-dihydropyrene (1c) in dichloroethane (DCE) solution were investigated by steady irradiation and nanosecond transient spectroscopy. Photorearrangements producing substituted oxepins, 2 occur via the singlet excited state of these compounds, while the phenolic products, 9-hydroxyphenanthrene (3a), 3-acetyl-9-hydroxyphenanthrene (3b), and 4-hydroxypyrene (3c) are formed via the triplet state. Phenol 3 formation from the triplet 1 sensitized by the triplet 3 (i.e. product sensitization) is proposed for the photorearrangement reactions of 1a and 1c, and this process is the only way phenol (3a) is formed because of the negligible intersystem crossing probability of 1a. No product sensitization occurs in the photorearrangement reaction of 1b.     

Studies on antiulcer drugs. III. Synthesis and antiulcer activities of imidazo[1,2-a]pyridinylethylbenzoxazoles and related compounds. A novel class of histamine H2-receptor antagonists.

A series of imidazo[1,2-a]pyridinylalkylbenzoxazole derivatives was synthesized and tested for histamine H2-receptor antagonist, gastric antisecretory and antiulcer activities. Some of 2-amino-6-[2-(imidazo[1,2-a]pyridin-2-yl)ethyl]benzoxazole derivatives were found to have good pharmacological activities. Among them, 2-amino-6-[2-(7-methoxy-3-methylimidazo[1,2-a]pyridin-2-yl)ethyl] benzoxazole (II-11) and 2-acetamido-6-[2-(7-methylimidazo[1,2-a]pyridin-2-yl)ethyl] benzoxazole (II-38) showed potent antisecretory and cytoprotective activity. The structure-activity relationships of these compounds are discussed.     

Diethylhydrogensilyl cyclic diethylsilylene derivatives in gas chromatography/mass spectrometry of hydroxylated steroids. III-Fragmentations of 5β-pregnane-17,20,21-triol derivatives

A reaction of N,O-bis-(diethylhydrogensilyl) trifluoroacetamide with 5β-pregnane-17,20,21-triols afforded diethylhydrogensilyl (DEHS) cyclic diethylsilylene (DES) derivatives. 5β-Pregnane-3α,17α,20β,21-tetraol yielded the 3α,21-bis-DEHS-17α,20β-DES compound, whereas the structure of the major product from its 20α isomer was assigned as the 3α,17α-bis-DEHS-20α,21-DES derivative, which would undergo facile isomerization to the unstable 3α,21-bis-DEHS-17α,20α-DES structure under electron ionization. Fragmentations of these DEHS-DES compounds are discussed on the basis of isotope labelling experiments, linked scanning data, and accurate mass measurements.     

Optically active antifungal azoles. VIII. Synthesis and antifungal activity of 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]- 3-(4-substituted phenyl)-2(1H,3H)-imidazolones and 2-imidazolidinones

New optically active antifungal azoles, 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl ]-3-(4- substituted phenyl)-2(1H,3H)-imidazolones (1,2) and 2-imidazolidinones (3,4), were prepared in a stereocontrolled manner from (1S)-1-[(2R)-2-(2,4- difluoro- and 2-fluorophenyl)-2-oxiranyl]ethanols (15, 16). Compounds 1-4 showed potent antifungal activity against Candida albicans in vitro and in vivo, as well as a broad antifungal spectrum for various fungi in vitro. Furthermore, the imidazolidinones, 3b--e and 4d, e, were found to exert extremely strong growth-inhibitory activity against Aspergillus fumigatus.