The structure of a mild and durable antihypertensive agent, 2-(2, 6-dichlorobenzylidenehydrazino)-1, 4, 5, 6-tetrahydropyrimidine hydrochloride (IIIa) (OT-24) was established by nuclear Overhauser effect (NOE) experiments. The anti-isomer (IIIa) was found to easily isomerize to the syn-isomer (IIIb) by irradiation of an ultraviolet ray on aqueous and methanol solution. Several related hydrazones were synthesized and their configuration was examined.

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Influence of local administration of serotonin on mitochondrial enzyme activities of rat skeletal muscle and action of anti-inflammatory drugs on it were studied. Two hundred μg of serotonin was injected into left gastrocnemius muscle. The right muscle was used for the control. The muscle was isolated 6 hr after serotonin injection and homogenized with 0.1 M Tris-HCl buffer containing 0.25 M sucrose (pH 7.4). The supernatant at 600×g of the homogenate was used as the enzyme source. Succinic dehydrogenase, malic dehydrogenase, lactic dehydrogenase, and ascorbate oxidase activities were determined in isotonic medium. Succinic dehydrogenase activity of the serotonin-injected muscle was about 3.2-fold of that of the control, but the other enzyme activities were not significantly changed. Aspirin, hydrocortisone, and indomethacin inhibited the increased activity of succinic dehydrogenase. Malic dehydrogenase and ascorbate oxidase activities of control and serotonin-injected muscle decreased by the administration of aspirin or hydrocortisone. Lactic dehydrogenase activity of both muscles was inhibited by the administration of aspirin, and increased by the administration of indomethacin.

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Dihydrocapsaicin (I) and capsaicin (II) were synthesized by a modified method of Crombie, and their acid parts were synthesized in a good yield by a one-step method, i.e., anodic synthesis introduced by Linstead, et al. Mass and nuclear magnetic resonance spectra of I and II were examined.

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Reaction of trialkylborane (I or II) with aromatic sulfonyl chloride derivatives (III-VIII) caused reductive alkylation and afforded the corresponding alkyl aryl sulfides (IX-XX) with a small quantity of mercaptans and disulfides. In this reaction, the yield of alkyl aryl sulfide was considerably better than that in the reaction with diphenyl sulfide (XXII) or sulfenyl chloride (XXIII) under the same condition. In the case of cyclohexyl phenyl sulfone (XXIV), a small amount of alkyl aryl sulfide was obtained, and diphenyl sulfone (XXV) did not react with trialkylborane. Since the reaction of trialkylborane with aromatic sulfonyl chloride was inhibited in the presence of a radical scavenger such as iodine or galvinoxyl, this reaction was considered to include a radical reaction.

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Pharmacological examination was made on bile secretion in rats of "Inchinkoto" ( ?? 〓 ?? ?? ), the most representative preparation for jaundice in Chinese medicine, and on each of its three constituent crude drugs (Gardeniae Fructus, Artemisiae Capillaris and Rhei Rhizoma). The extract of Gardeniae Fructus hardly increased bile secretion, while genipin, an agiycone of geniposide which is present in this crude drug, markedly increased it. Essential oils from Artemisiae Capillaris (Spica) and its oil-free extract increased bile secretion and 6, 7-dimethylaesculetin, which is one of the components of this crude drug, also showed the same effect. On the contrary, the extract of Rhei Rhizoma was not effective in this test. The extract prepared from "Inchinko-to" increased bile secretion and its action seemed to depend highly on that induced by Artemisiae Capillaris (Spica). The combination of genipin and 6, 7-dimethyl-aesculetin synergistically increased bile secretion.

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3-Alkoxyisocarbostyrils (IIa-e) were synthesized from 2-cyanomethylbenzoate (I) by heating with various primary alcohols in the presence of an equivalent amount of sodium. It was found that 3-methoxyisocarbostyril (IIa) reacted easily with hydrazine hydrate and mono- or di-substituted amines to give the corresponding 3-substituted aminoisocarbostyrils (VIIIa-i) in a good yield.

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The reaction of 2-methylhomophthalimide with diazomethane in ether resulted in the formation of spiropropane derivatives, such as spiro[cyclopropane-1, 4'-(2'-methyl-homophthalimide)] (II) and spiro[2-methylcyclopropane-1, 4'-(2'-methylhomophthalimide)] (III) and a compound (IV), the structure of which was still uncertain. This is a novel type of a reaction and has never been reported.

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A new series of compounds, bis(2-hydroxybenzamido)benzoic acid derivatives, was examined for their inhibitory effect on homocytotropic reaginic antibody-mediated passive cutaneous anaphylaxis reaction in rats. When injected intravenously, 2, 4-bis(2-hydroxybenzamido)benzoic acid (AB-23) and 3, 5-bis(2-hydroxybenzamido)benzoic acid (AB-19) showed marked inhibition of this reaction. The inhibitory activity of the former was about three times stronger than that of the latter. When administered orally, 2, 4-bis(2-acetoxybenzamido)benzoic acid (AB-50), a diacetylated form of AB-23, was the most effective among all the compounds tested. The usefulness of AB-50 as an oral antiasthmatic drug was discussed.

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π-Complex of o-hydroxybiphenyl was examined by the nuclear magnetic resonance (NMR) technique. Chemical shifts, nuclear Overhauser effect (NOE), and T₁ showed positive results. The proton spin-lattice relaxation time was measured over the temperature range of -52° to 80°, and the maximum relaxation time was observed at about 35°. It was found that the dipole-dipole relaxation time dominates at low temperatures and in the solvent which has a strong solvent-solute interaction. The spin-rotation relaxation time dominates at high temperatures and near the boiling point of the solution.

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Reduction of homophthalimide derivatives (IIa, IIb, and IIc) with NaBH₄ gave 3, 4-dihydroisocarbostyril derivatives (IIIa, IIIb, and IIIc) which were converted to isocarbostyril derivatives (VIa, VIb, and VIc) by hydrochloric acid in ethanol. VIc was converted into 8-oxoprotoberberine derivative (VII). Hydrogenation of VIc with 10% Pd-C gave the amide (VIII). Bischler-Napieralski reaction of VIII followed by reduction with NaBH₄ gave the dibenzoquinolizine derivative (IX).

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The two isomers (IIa and IIb) of 2-methyl-7-amino-cis-decahydroisoquinoline, which were obtained by catalytic hydrogenation of 2-methyl-7-amino-1, 2, 3, 4-tetrahydroisoquinoline (I), were also prepared from the corresponding decahydroisoquinolinols (IIIb and IIIa) via their tosylates. Deamination of IIa or IIb with nitrous acid was found to give a product which contained a mixture of alcohols (IIIa and IIIb) and the olefinic compounds (V and VI). Some mechanistic considerations were also presented for the deamination reaction.

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The synthesis of a series of 2-amino-1, 1-dialkyl-7-methoxy-1, 2, 3, 4-tetrahydronaphthalenes and the related compounds is described and their analgesic activities are reported. As measured by the acetic acid writhing method for the preliminary screening test, the introduction of geminal diethyl groups in the methylene at position 1 of 2-amino-1, 2, 3, 4-tetrahydronaphthalene enhances the analgesic activities. The substitution in 2-amino group decreases the activities. ED₅0 values of four compounds were checked by the acetic acid writhing, electric stimulation, and hot plate methods.

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An attempt was made to synthesize flavone derivatives (III) from 2'-hydroxychalcone derivatives (I) by using platinated palladium-carbon catalyst and the oxygen from amine N-oxide as the oxidation agent. III was obtained in 20% yield by the use of pyridine 1-oxide (IIa). The yield was poor when triethylamine N-oxide (IIb) was used but the reaction progressed at room temperature. The hydrogenated product, 2'-hydroxydihydrochalcone, and the cyclization product to a five-membered ring, 2-benzylidenecoumaranone, were not obtained in these reactions. It was assumed that ring closure took place without going through flavanone when the N-oxide was used.

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3, 3-Ethylenedioxy-5α, 6α-epoxyandrostan-17β-ol (I), derived from testosterone, was oxidized with glacial acetic acid and then hydrolyzed with 80% acetic acid to give 6β-hydroxytestosterone 6-acetate (IIb). The conversion of IIb to 6α-hydroxytestosterone 6-acetate (IIa) was achieved by treatment with HCl gas in CHCl₃ containing EtOH (0.7%). The trityl derivatives of IIa and IIb were hydrolyzed with K₂CO₃ to produce 6α (or 6β)-hydroxy-17β-trityloxy-4-androsten-3-one (IVa, IVb), respectively. The succinylation of IVa and IVb with succinic anhydride followed by hydrolysis with 50% acetic acid afforded 6α (or 6β)-hydroxytestosterone 6-hemisuccinate (VIa, VIb), respectively. VIa and VIb were attached to bovine serum albumin via mixed anhydride coupling using tributy1amine and isobutyl chloroformate.

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Surface-active properties and molecular aggregate formation of glycyrrhizic acid (GA) were examined by the measurement of surface tension, light scattering, light absorption of Rhodamine 6G (R-6G) solution or iodine solution, and fluorescence of R-6G solution. It was found that each physico-chemical property plotted against GA concentration showed a transition at a certain concentration, which indicated the formation of molecular aggegrates. The critical micelle concentration (CMC) values determined by these different methods were in good agreement. The spectral change method using the aqueous dye solution or the aqueous iodine solution seemed to be convenient because of the ease of its experiment. However, the definition of CMC by this method is somewhat arbitrary and the CMC value is sometimes influenced by the concentration of dye or iodine added. It is therefore essential to choose a suitable procedure for determining the exact CMC value from the plots of absorbance vs. concentration and to correct the CMC value for the effect of additives.

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With the Schiff base as a model compound, compounds possessing an azoxymethine group were reacted with pyridine 1-oxide (IIa) and triethylamine N-oxide (IIb), in the presence of a platinated palladium-carbon catalyst. Reaction of N-benzylideneaniline (I) with IIa gave benzanilide (III) and that of I with IIb gave 2-phenylquinoline (V) and not III. Reaction of I with fumaric acid and paraldehyde, in the presence of platinated palladium-carbon catalyst gave V in 23.3% yield. Reaction of 2-benzylideneaminophenol (VII) with IIa gave a small amount of 2-phenylbenzoxazole (VIII), while that with IIb for 7 days at room temperature gave VIII in 6% yield. It is considered that oxidation becomes too strong in the reaction of VII with an N-oxide. Reaction of VII by bubbling air through its xylene solution, using the platinated palladium-carbon catalyst, results in approximately quantitative yield of VIII. These reactions were also examined with the derivatives of VII.

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Catalytic effect of some kinds of metal ions on the reaction of o-toluenediazonium sulfate and thiocyanate ion was examined by determination of o-tolyl thiocyanate produced, using gas-liquid chromatography. The catalytic action of zinc, cupric, ferrous, mercuric, cuprous, and mercurous ions was effective but that of other metal ions, such as ferric, potassium, lead, silver, cobalt, cadmium, nickel, uranyl, chromium, molybdate, tungstate, manganease and stannous ions, was weak or negligible. The catalytic reaction was affected by pH of the solution and the molar ratio of the reactants. Good yield of o-tolyl thiocyanate was obtained with Zn²⁺ and Fe²⁺ at pH 1-3, and with Cu²⁺ at pH 8.5, and the yield was better, the larger the amount of thiocyanate ion added. As a catalyst, zinc ion was found to be the best. A new method of mixing one mol of o-toluenediazonium sulfate, 4 or more mol of potassium thiocyanate, and 1 mol of zinc sulfate solution at pH 1-3 and allowing them to react is recommended for the synthesis of o-tolyl thiocyanate, which is obtained in ca. 50% yield by this procedure.

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From the leaves of Magnolia obovata, α- and β-pinene, camphene, limonene, bornyl acetate (III), caryophyllene (IV), caryophyllene epoxide (V), and chavicol (VII) were identified as components of its essential oil, and ethyl palmitate (trace), ethyl stearate (trace), and palmitic acid (VI) were also isolated and characterized. The main component of the essential oil of fresh leaves was IV, while that of dried leaves was V. The conversion of IV into V advanced with drying of the leaves and ratio of V to the total amount of IV + V reached 85% after drying for 30 days. From the observation of the conversion of IV, impregnated into filter papers under various conditions, the conversion was found to be caused by air oxidation.

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Pharmacological properties of 32 s-triazine derivatives were examined and it's results are summarized as follows. 1) Twenty compounds showed depressant action against spontaneous motor activity. Among these, 4-substituted-2-amino-6-trifluoromethyl-s-triazine derivatives, I (4-iso-propylamino), IV (4-cyclohexylamino), IX (4- (4-methylpiperazin-1-yl)), X (4- (4- (2-hydroxyethyl)-piperazin-1-yl)), and 2-benzalhydrazino-4-tert-butyl-6-piperazino-s-triazine (XXXV) showed a significant effect below the dose level which caused muscle relaxation. 2) IV, X, and 2-hydrazino-4-piperazino-6-trifluoromethyl-s-triazine (XV) showed a significant anti-morphine action. 3) IX, 2-hydrazino-4-(4-acetylpiperazin-1-yl)-6-trifluoromethyl-s-triazine (XIII), 2-hydrazino-4-(4-methylpiperazin-1-yl)-6-trifluoromethyl-s-triazine (XIV), 2-benzalhydrazino-4-(4-(2-hydroxyethyl)-piperazin-1-yl))-6-trifluoromethyl-s-triazine (XXXIII), and XXXV strongly potentiated hexobarbital sleeping time. 4) Central depressant action of triazine derivatives was mainly characterized by sedative action accompanied by weak muscle relaxant and faint anti-convulsant action. Considering these results, it seems difficult to define the triazine derivatives as a specific type of a tranquilizer, although, IX, X, and XV exhibited cataleptogenic activity typical of major tranquilizer. 5) IX, X, and XXXV inhibited acetic acid-induced writhing and their activity was comparable to that of aminopyrine. 6) 2-Amino-4-p-chloroanilino-6-trifluoromethyl-s-triazine (VI), XIV, and 2-benzalhydrazino-4-morphorino-6-trifluoromethyl-s-triazine (XXX) showed moderate hypotensive actions. 7) I, IV, XIV, 2-isopropylamino-4-morphorino-6-trifluoromethyl-s-triazine (XLI), and 2-isopropylamino-4-methylamino-6-trifluoromethyl-s-triazine (XLIII) showed adrenolytic activities. 8) 2-Amino-4-phenethylamino-6-trifluoromethyl-s-triazine (V), 2-dimethylamino-4-(4-methylpiperazin-1-yl)-6-trifluoromethyl-s-triazine (XXXIX) and XLIII expressed moderate anti-serotonin effects but anti-cholinergic or anti-histaminic actions were not observed.

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The relation between oxidation rate of ascorbic acid and amount of oxygen dissolved in aqueous solutions of various solubilizing agents was examined. The oxidation rate of ascorbic acid was determined by the Warburg apparatus. In aqueous solutions of ethylene glycol, diethylene glycol, and triethylene glycol, having a hydrophilic group, the amount of dissolved oxygen and the oxidation rate of ascorbic acid were found to decrease with increasing concentration of these agents. In contrast, aqueous solutions of Cellosolve, isopropyl-Cellosolve, butyl-Cellosolve, methyl-Carbitol, Carbitol, butyl-Carbitol, dipropylene glycol, 1-methoxy-2-propanol, and hexylene glycol, having both hydrophilic and hydrophobic groups, showed a minimum point in the amount of dissolved oxygen and the oxidation rate of ascorbic acid. These experimental results indicate that these solubilizing agents undergo association in these mixtures at the minimum concentration, decrease the ability of the solution to dissolve or diffuse oxygen at this concentration, and this is probably the reason why there is a maximum in stability of ascorbic acid at this concentration.

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4-[N-(N', N'-Dialkyl) glycyl-N-phenyl]amino-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-ones (6, 7, 8) were synthesized starting from 1-methyl-2-phenyl-1, 2, 3, 10-tetrahydro-4H-pyrazolo [3, 4-c][1, 5] benzothiazepin-3-one (1). Several 2- or 4-substituted-N-(4-substituted-2-methyl-5-oxo-1-phenyl-3-pyrazolin-3-yl)methylanilines were synthesized. Treatment of methyl N-(2-methyl-5-oxo-1-phenyl-3-pyrazolin-3-yl)methylanthranilate (22) with ethyl polyphosphate afforded methyl N-(2-methyl-5-oxo-1-phenyl-3-pyrazolin-3-yl)methyl-N-ethylanthranilate (24) in 55.5% yield.

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The acid dissociation constants and stability constants of metal chelates and protonated complexes of 2-aminoethylphosphonic acid (H₂NCH₂CH₂PO₃H₂) and its related compounds (aminomethylphosphonic acid, 3-aminopropylphosphonic acid and O-phosphoethanolamine), were measured by potentiometry at 25° and μ=0.1 (NaClO₄) in aqueous solution. The acid dissociation constants were compared with those of aminocarboxylic acids, aminosulfonic acids, and related compounds. The stability of complexes was in the order of Mn<Co<Ni<Cu>Zn, and these values were influenced by the ligand basicity and the chelate size. It was revealed that the stability constant (log K_ML) of aminophosphonic acids lay between those of glycine and adenosine triphosphate (ATP) and aminophosphonic acids showed comparatively low selectivity to bivalent metal ions used.

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Three iridoid glycosides, sweroside, loganin and cantleyoside, were isolated from the fresh roots of Scabiosa japonica MIQ.

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Triterpenoids of the stems of three plants of Spiraea species (Rosaceae) were examined from the chemotaxonomical point of view. Glutinol and taraxerol, from S.Thumbergii SIEB., glutinone and taraxerol, from S.tosaensis YATABE, and betulinic acid and 3-epibetulinic acid from S.cantoniensis LOUR, were isolated and identified.

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The crystalline compound, obtained during the separation of choline and acetylcholine reineckates from the aqueous extract of Pueraria radix, was found to be a by-product formed during the porification of choline reineckate with acetone used as the solvent. This by-product was identified as diacetonamine reineckate. It was revealed that when reineckates in general are allowed to stand in acetone, the reineckate ion [Cr-(NH₃)₂(SCN)₄]^- liberates NH₃ group which adds to mesityl oxide, (CH₃)₂-C=CH-CO-CH₃, the dimer of acetone, to form diacetonamine, (CH₃)₂-C(NH₂)-CH₂-CO-CH₃.

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The roots of Sophora japonica L.afforded anhydropisatin (flemichapparin B) (I), iriso1idone (II), 5, 7-dihydroxy-3', 4'-methylenedioxyisoflavone (III), and biochanin A (IV), with d-maackiain and β-sitosterol.

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