Thermolysis of copper (II) complex of tryptophan in various solvents led to the formation of tryptamine and indole as a by-product. Similar treatment of copper (II) complex of 1, 2, 3, 4-tetrahydro-1-methyl-β-carboline-3-carboxylic acid (V) afforded harman (VII) which would be formed by air-oxidation of 1, 2, 3, 4-tetrahydroharman (VI). Thermolysis of I and V with copper powder as a catalyst or without catalyst was also examined.
There is a lipid monolayer on the surface of the alveolus of animal lung. It decreases the surface tension of water in the alveolus and has an important effect on the function of the lung. Lipid separated from cow lung tissue was found to contain dipalmitoyl phosphatidyl choline in a high concentration. The monolayer of the lung phosphatidyl choline exhibited a marked hysteresis, and this hysteresis was considered to be correlated with the lung mechanics. It was found that this hysteresis became larger when the monolayer was compressed to higher surface pressure, and also that it depended on temperature and was the largest at about 30°. It was concluded that the hysteresis was caused by the phase transition of the monolayer by compression. The behavior of the monolayers of phosphatidyl ethanolamine and sphingomyeline separated from cow lung tissue was also discussed.
Some properties of dopamine β-hydroxylase (DβH) in the homogenate of bovine adrenal medulla and inhibitory effects of thiourea derivatives on DβH were examined. Enzymic formation of norsynephrine from tyramine in the homogenate of the adrenal medulla was linear with respect to time (up to 30 min) and protein concentration (up to 160 μg). By typical Lineweaver-Burk plots, Km value was calculated to be 4×10-3M. Among the compounds tested, N-phenyl-N'-[3-(4H-1, 2, 4-triazolyl)]thiourea and N-n-butyl-N'-[3-(4H-1, 2, 4-triazolyl)]thiourea were effective inhibitors, and inhibition by the latter was non-competitive with substrate tyramine. Structure-activity relationship between thiourea derivatives and the inhibitory effect on DβH was discussed.
Sodium cyanide was reacted with 2-cyano-3, 3-bis(methylthio)acrylonitrile (Ia) and methyl 2-cyano-3, 3-bis(methylthio)acrylate (Ib), the derivatives of ketenethioacetal, and 2, 3-dicyano-3-methylthioacrylonitrile (IIa), and cis and trans compounds of methyl 2, 3-dicyano-3-(methylthio)acrylate (IIb, c) were obtained. Reaction of these compounds (IIa, b, c) with nucleophilic reagents (amines and active methylenes) gave the corresponding compounds in which methylthio group had been substituted, in a good yield.
N-Alkylaminopropyl-1, 1-diphenylmethylamines and N-alkylaminoethylamines were synthesized and some pharmacological properties of these compounds were examined. Local anesthetic activities of IVa, Va, Ve, and Vf were more potent than that of procaine on the surface anesthesia in guinea pig cornea, but less potent than that of lidocaine. Vc had approximately the same potency as lidocaine. On the infiltration anesthesia in guinea pigs, Va, Vc, Ve, and Vf had almost the same potency of procaine. All of these compounds, however, had an intradermal irritancy in the rabbit skin. IVa, Va, and Ve produced marked inhibitory effect on the acetic acid-induced writhing in mice, and IVa, Vc, and Vd increased threshold of the tail pain response in mice. Vc and Vd were found to have an antitussive activity by the mechanically stimulating method in guinea pigs. Tremor caused by tremorine in mice was inhibited by IVa, but not by other compounds. All the test compounds produced a fall in the blood pressure of anesthetized rats and rabbits, and this action was not inhibited by pretreatment with atropine and diphenhydramine, respectively.
The phase diagram of the cholesterol-cetyl alcohol system was determined by means of optical microscopy, differential thermal analysis, and dielectric measurement. A mixture of cholesterol and cetyl alcohol took a liquid-crystalline state at a limited range of composition (25-45 mole% of cholesterol) although each of pure components did not take the liquid-crystalline state. The dielectric properties of the mixture was examined and the dielectric constant and the dielectric loss were found to take maximum values at the temperature where the fusion begins. Dielectric loss is mainly due to relaxation in the solid phase. In the range from the initial melting point to the final melting point of the solid, the mixtures have dielectric relaxation smaller than that of the solid phase. In the liquid crystal and the isotropic liquid phase, the mixture does not show dielectric relaxation so that the dielectric loss is due to conduction.
Among the 352 kinds of amino acid derivatives obtained from amino acids, N-2-fluorenesulfonyl-β-alanine and N-2-naphthylaminomethyl-L-alanine were found to have a good anti-influenza virus activity. The known antiviral agents had to be given within a short period after viral infection to be effective but these compounds showed a significant effect by administration even 72 hr after viral infection. The action mechanism of these compounds was considered to be the sum of two biphasic effects ; one of inhibiting viral multiplication and the other of inhibiting specific inflammation accompanying viral infection.
Absorption of benzoic acid, phenol, phenobarbital, and pentobarbital from water by goldfish was studied kinetically. The absorption membrane of goldfish was thought to be like a lipid membrane for the absorption of these chemicals at various pH. Addition of urea (1M) to the water promoted absorption rate of each chemical, as was the case with salicylic acid.3) There was a difference in the order of absorption rate of these chemicals between goldfish and their intestinal absorption in rats.4) The ratio of equilibrium concentration of the chemicals between goldfish and water did not agree with the pH-partition equilibrium theory, either in the variance of pH or of chemicals. The amount of absorption estimated from the decrease of chemicals in water was completely recovered in the homogenate of goldfish. Concentration of the chemicals in goldfish organs was the highest in the gills for all the chemicals tested. The observed excretion rate of benzoic acid from goldfish in fresh water, after the absorption experiment, was consistent with the kinetic theory during the first 2 min but decreased rapidly thereafter.
Absorption, distribution, and excretion of o-hexyloxybenzamide (HBA) were studied in rats by using <14>C-labeled compound, which was prepared from <14>C-salicylic acid. The radioactivity in blood reached maximum level at 2 hr after intraperitoneal administration of the compound dissolved in soybean oil. The level of radioactivity in blood was as low as that in tissues. The rats excreted about 77% of the injected radioactivity in urine, and about 15% in feces within 72 hr. In the case of percutaneous administration of HBA in ointment, about 16% of the administered radioactivity was excreted in urine within 72 hr and about 73% of the administered radioactivity remained at the site of application. In both routes of administration, distribution of radioactivity in rat tissue was more highly located in the kidney and liver than in other tissues. Examination of metabolite in urine showed that no unaltered compound could be detected and main metabolites might be glucuronides of carboxylic acid-type and alcoholic type derivatives derived from the hexyloxy residue of HBA.
N-Methyl-N, N-bis(3-methylsulfonyloxypropyl)amine 4, 4'-biphenyldisulfonate (838D) and bis(3-methylsulfonyloxypropyl)amine p-toluenesulfonate (864T) are a cross between nitrogen mustard and busulfan. On the cultured Yoshida sarcoma cells, 50% growth inhibition concentration (IC50) of 838D, 864T, and nitrogen mustard was 6.1×10-3 mM, 1.4×10-2 mM and 2×10-5 mM, respectively. Busulfan did not give the value of IC50 in this condition. They were more effective on Yoshida sarcoma and ascites hepatoma AH 13 than on AH 66 or AH 7974. Syntheses of nucleic acid and protein in Yoshida sarcoma cells were not influenced by the addition of 864T or nitrogen mustard at concentrations above IC50. The entry of tumor cells into mitosis was inhibited at the same concentration of these compounds. In the experiments, 864T showed activities similar to that of nitrogen mustard. Characteristic activities of 864T on rats bearing transplantable tumors were not revealed in experiments using cultured tumor cells.
The structures of two steroidal substances, G4 and S4, isolated3) from the fresh aerial parts of Dioscorea tenuipes FRANCH. et SAVAT. (Dioscoreaceae) were investigated. G4 mp 217-218° (decomp.), [α]D-55.0°, was characterized as 3-methoxalyldiotigenin 4-acetate (V), and S4, mp 205-206° (decomp.), [α]D+19.0°, was presumed to be a complex (VI) consisting of one mole each of V, Mg(OH)2, and H2O. They are first spirostanol methoxalate and its magnesium complex ever found in nature.
Five metabolites appearing in the urine of the rabbit fed bromazepam were isolated; these are 2-(2-amino-5-bromobenzoyl)pyridine (ABBP), 2-(2-amino-5-bromo-3-hydroxybenzoyl)pyridine (3-OH ABBP), 3-hydroxybromazepam, and two new matabolites, 9-hydroxybromazepam and 5'-hydroxybromazepam. The new metabolites were characterized by thin-layer chromatography (TLC) ; elemental analysis, and infrared, nuclear magnetic resonance, and mass spectrometries. Metabolites, which were excreted mainly as conjugates of glucuronic acid and/or sulfuric acid, were measured by preparative TLC and characteristic colorimetric method after enzymic hydrolysis of the conjugates. Urinary excretion of bromazepam and its metabolites have been studied in dogs, rabbits, mice, rats and guinea pigs after massive doses of bromazepam. The conjugated 3-OH ABBP was the major metabolite in rabbits (17.1% of the dose) and dogs (6.2% of the dose) during 24 hr. The major metabolites found in rats, however, were the conjugated form of 3-OH ABBP (5.3% of the dose), 5'-hydroxybromazepam (4.2% of the dose), and ABBP (3.8% of the dose), and 9-hydroxybromazepam was not excreted. In mice the major metabolite was the unconjugated form of 3-hydroxybromazepam (7.5% of the dose). In guinea pigs, two unknown metabolites, besides the above five metabolites, were excreted, and it was confirmed that one of them was benzhydrol analog of ABBP. When intraperitoneal injection was compared with oral administration of the same dose in the rabbit, the urinary excretion of the ring-cleaved metabolites, ABBP and 3- OH ABBP, decreased, but that of the others, 3-hydroxybromazepam and 5'-hydroxybromazepam, increased. On the basis of these data, pathways of bromazepam were postulated (Chart 1). Quantitative differences in the urinary metabolites of bromazepam in each species was clearly observed during the first 24-hr period.
Mercuric acetate oxidation of deoxynupharidine (I) gave in oily product (II) which formed a crystalline perchlorate (III). When treated with sodium borohydride, III afforded trans-and cis-quinolizidine derivatives (IVa and IVb). Formula II' was assigned to the structure of II from the infrared spectral data of II, IVa, and IVb.
A new base, dehydronantenine, was isolated from the tree bark of Nandina domestica THUNB., and its structure was formulated as (I) from ultraviolet and nuclear magnetic resonance spectra, especially by the application of nuclear Overhauser effect. I was synthesized by the dehydrogenation reaction of O-methyldomesticine (II) and its structure was proved. One kind of a neutral substance was also isolated and it was confirmed to be (-)-episyringaresinol (III).
Two synthetic ways to quisqualic acid (I) from 3, 5-dioxo-1, 2, 4-oxadiazolidine (V) and from methyl 3-chloro-2-benzoxycarbonylaminopropionate (X) are described. DL-2-Amino-3-(1-hydroxyureido)propionic acid (DL-II) and L-2-amino-4-(3-hydroxyureido)-butyric acid (VI) were also synthesized.
Oral or intraperitoneal administration of bis(3-methylsulfonyloxypropyl)amine p-toluenesulfonate (864-T) and N-methyl-N, N-bis(3-methylsulfonyloxypropyl)amine 4, 4'-biphenyldisulfonate (838-D) for 3 consecutive days before or after immunization suppressed the number of 19S hemolysin plaque-forming cells (HPFC) in the spleen as well as the circulating antibodies, hemagglutinin and hemolysin, of mice on day 4 after immunization with sheep red blood cells. In single administration, the maximum inhibition was found on day 0 in 864-T and 838-D, on day 2 in cyclophosphamide, and on day 3 in busulfan. 864-T and 838-D were classified in the different type from cyclophosphamide or busulfan. Seven-S HPFC were not suppressed by 864-T, 838-D, nitrogen mustard N-oxide, busulfan, or 6-mercaptopurine in the administration for 3 consecutive days from day 0 or from day 4, and only cyclophosphamide inhibited it when administered from day 4. 864-T and 838-D did not affect the carbon clearance in mice.
Free amino acids in " bear gall" and the related crude drugs were determined by aminoacid analyzer (Hitachi Model KLA-3B). On the basis of these data, "bear galls" were divided into two groups with respect to the patterns of amino acids contained, and the pattern of amino acids in each group was characteristic and distinctive from those of domestic hog, bovine, and wild boar galls. The glycine/taurine ratios in these galls were significantly correlated to the ratios of glycine- and taurine-conjugated bile acids.
Acute toxicity and sedative action of water-soluble fractions obtained from Zizyphus seeds were estimated in mice. Very weak toxic effect was found in all the fractions. Fractions DZ-191, DZ-193, and DZ-18 showed some sedative action in a climbing test. Significant potentiation of hexobarbital-induced anesthesia was found in DZ-191, DZ-193, and ZM fractions. Significant antagonistic effect to caffeine-induced hyperactivity was found in DZ-193 and ZM fractions. Only ZM showed a slight decrease of hole crossing after repeated oral administration for 3 days.
Photoelectron spectra of sodium and/or piperidine salts of six kinds of σ complexes obtained from either 1, 3, 5-trinitrobenzene or picric acid were measured. The results showed that binding energies of 1 s electrons of nitrogen atoms of a complex differ distinctly from each other, but those of oxygen atoms differ slightly and those of carbon atoms are approximately equal. The difference of binding energies of nitrogen atoms of three nitro groups was attributed to the different degree of polarization of these groups in a crystalline form. Charge densities of nitrogen atoms of all σ complexes measured were estimated from the correlation curve established between binding energies of nitrogen atoms of several compounds and their charge densities calculated by the CNDO/2 method. Disagreement was noted in charge densities of complex II calculated by the CNDO/2 method and that estimated by the present method.
The essential oil of Mosla methylchavicolifera FUJITA (Labiatae) was examined by gas chromatography and infrared spectrometry, and its components were compared with those of Agastache rugosa O. KUNTZE. The similarity of components of these two essential oils will show the same stage of appearance of homologous element in the formation of essential oils controlled by the homologous series of genes. These phenomena are also explained by assuming that parallel evolution of essential oil formation is in the same stage.
2, 3-Methylenedioxynaphthalene (VIII), mp 97-99°, which was first isolated from Cinnamomum camphora SIEB., was synthesized from piperonal (I) via seven steps. In the course of this study, reduction of V to VI was successfully achieved by PdCl2-NaBH4 without affecting the carboxyl group. All spectra data (ultraviolet, infrared, mass) of synthesized VIII were almost identical with those of natural product and its nuclear magnetic resonance spectrum also agreed with the structure of VIII. As a result, the structure of natural VIII was synthetically confirmed.
Gas chromatographic method is devised for the determination of tetracaine N-oxide, a metabolite of tetracaine, in urine. Tetracaine N-oxide is converted to methyl p-(N-methyl-N-butylamino) benzoate by treating with trimethylanilinium hydroxide, and it shows satisfactory sensitivity to flame ionization detector. The calibration curve for quantitation is constructed with caffeine as an internal standard. Tetracaine N-oxide was separated from urine by extraction with chloroform. A known amount of this compound added to urine was recovered at the rate of ca. 69% by the proposed procedure.
It was demonstrated that an aqueous ethanolic extract of the fruits of Prunus japonica THUNB., dry seeds of which have been used as a diuretic, had a purgative activity. A physiologically active constituent was isolated as crystals, and named "prunuside". Prunuside (I) was hydrolysed to one mole each of kaempferol, glucose, rhamnose, and acetic acid, or gave 3-rhamnoglucosylkaempferol (IV) by mild hydrolysis with 2% aqueous NaOH solution. It was thereby clarified that the chemical structure of I was a monoacetyl derivative of IV. IV had already been isolated from Calystegia japonica CHOISY, Rhamnus japonica MAXIM., and Rosa multiflora THUNB., which are known as purgative crude drugs. The purgative activity of I was far stronger than that of IV and I may be attractive as a new active constituent.