It was found that taurocholic acid and glycocholic acid, the bile components, had the effect of accelerating absorption of salicylic acid derivatives from rat digestive tract, same as taurine and glycine reported previously. In order to examine the action of bile juice itself in the absorption of salicylic acid derivatives, experiments were carried out by ligation of bile duct (in rats) and it was found that the secreted bile had the reverse effect of inhibiting the absorption of salicylic acid derivatives from rat small intestine, and that cholic acid among the bile components had the same effect. It was thereby assumed that bile juice and bile components had repulsive and homologic actions, and were in complicated correlation. The bile juice once taken out of a living body has a different action from bile juice in secreting state and had no action of inhibiting the absorption of salicylic acid derivatives from small intestine (of a rat).
In order to examine the analgesic action of benzofuran derivatives, 4, 5, 7-trisubstituted 2-monoalkylaminomethyl-2, 3-dihydrobenzofurans were synthesized. Analgesic effect of 32 of these compounds was tested by the electric shock method and inhibition of writhing syndrome elicited by acetic acid. 7-Methoxy-2-methylaminomethyl-2, 3-dihydrobenzofuran (35) showed the strongest analgesic activity with only a weak acute toxicity
Polarographic behaviors of androst-4-ene-3, 6, 17-trione (I) in aqueous dimethylformamide and acetonitrile containing 0.1 M LiCl as a supporting electrolyte were examined. In 50% acetonitrile solution, I showed one reduction wave corresponding to two electrons at -0.755 V vs. S.C.E., whereas in 50% dimethylformamide solution, two reduction waves appeared, involving two electrons in all at -0.810 and -1.485 V vs. S.C.E. In the case of aqueous dimethylformamide, the total limiting current was constant and the height ratio of the 1st wave to the 2nd was dependent on dimethylformamide concentration. The controlled potential electrolysis of I in aqueous dimethylformamide resulted in the formation of 5α-androstane-3, 6, 17-trione (IX). These results together with the ultraviolet spectral data revealed that in dimethylformamide solution, I exists in the keto-enol equilibrated state, and the 1st and 2nd waves are ascribable to the reduction of keto and 6-enol forms, respectively.
The insoluble metal-5'-AMP complexes were isolated and the metal coordination sites on 5'-AMP were investigated by infrared absorption and nuclear magnetic resonance (NMR) spectra. Spectral changes in complex formation were discussed on the basis of absorption bands of the adenine ring moiety (1700-1600 cm-1) and phosphate groups (1200-900 cm-1) in comparison with those of 5'-AMP and 5'-AMP sodium salt which were prepared from various pH solutions. Shifts of C=N+ at 1690 cm-1 to 1705 cm-1 and 1675 cm-1 in complexation with Pb2+ and Cd2+, respectively, and a little change in 1200-900 cm-1 showed that the adenine ring moiety and also the phosphate group are the sites of coordination of these metals. Other metals such as Fe3+, Al3+, UO22+, ZrO2+, and Ag+ coordinate mainly the phosphate group of 5'-AMP. The coordination of Pb2+ and Cd2+ to the adenine ring moiety was confirmed clearly by NMR spectra, in DMSO-d6 but the site of coordination in the adenine ring could not be determined.
Pharmacological properties of 2-trimethylaminoethyl-1'-methylisothiuronium bromide hydrobromide (MTMA) and 2-trimethylaminoethyl-1'-ethylisothiuronium bromide hydrobromide (ETMA), derivatives of 2-trimethylaminoethylisothiuronium bromide hydrobromide (TMAET), on autonomic nervous system were examined. MTMA gave a rise in blood pressure of the rat and cat, and caused a contraction of nictitating membrane of a cat. The pressor action and contraction of nictitating membrane were blocked by hexamethonium. On the other hand, ETMA showed depressor action and blocked the pressor action induced by acetylcholine and DMPP in rat and cat. Contraction of nictitating membrane induced by electrical stimulating and acetylcholine was blocked by ETMA. MTMA and ETMA showed a weak negative inotropic action on the heart preparation of guinea pig, but ETMA was weaker than MTMA. MTMA showed a stimulating action on the isolated guinea pig ileum. Contraction of ileum was inhibited by hexamethonium and atropine. On the other hand, ETMA had no stimulating action but blocked the contraction of ileum induced by nicotine. The contraction of vas deferens of a guinea pig induced by electrical stimulation of preganglionic fiber of hypogastric nerve was potentiated by MTMA and inhibited by ETMA. Acute toxicity in mice was also tested.
Brief heating of α-kainic acid (I) and α-allokainic acid (II) with ninhydrin in water solution first afforded the products C and B respectively. The former (C) was readily epimerized in hot methanol or dimethyl sulfoxide to yield the antipode of the latter (B). Further heating of the product C in a phosphate buffer gave the product E via intermediates D and D'. The structures of the products B, C, and E were elucidated as VI, VII, and VIII, respectively, and those of the intermediates D and D' are discussed. Reaction sequences of α-kainic acid and α-allokainic acid with ninhydrin in a phosphate buffer at 60° were followed by means of ultraviolet spectra.
3, 3-Bis(substituted methyl)-6-chloro-3, 4-dihydro-2H-1, 2, 4-benzothiadiazine-7-sulfonamide 1, 1-dioxides were obtained by the condensation of 4-amino-6-chloro-m-benzenedisulfonamide (III) with 1, 3-disubstituted acetones. Condensation of III with 1, 3-diacetoxyacetone or 1, 3-dihydroxyacetone (XII) gave 6-chloro-3-(1-hydroxyethyl)-2H-1, 2, 4-benzothiadiazine-7-sulfonamide 1, 1-dioxide. When N-methyl-ο-aminobenzenesulfonamides were treated with XII, 3-acetyl-3, 4-dihydro-2H-1, 2, 4-benzothiadiazines were obtained. Condensation of ο-aminobenzenesulfonamide with XII afforded 3-acetyl-3, 4-dihydro-2H-1, 2, 4-benzothiadiazine 1, 1-dioxide (XX), whose treatment with alkali converted it to 3-(1-hydroxyethyl)-2H-1, 2, 4-benzothiadiazine 1, 1-dioxide. Some of these products showed diuretic action in rats.
Examinations were made on the root constituents of three cultivated Japanese valerians, "Hokkai-kisso" which is produced in Hokkaido and solely circulated in the present crude drug market, "Azamiba-kisso" which was once cultivated in Kanto district, and the valerian which has been cultivated at Toyama University, and a number of sesquiterpenoids has been isolated or detected. These valerians are characterized by containing sesquiterpenoids of the kessane skeleton (in particular kessyl glycol) in a large quantity. Further, presence of 2-isopropyl-4-methylanisole having a m-cymene skelton has been demonstrated in nature for the first time.
8-Unsubstituted-3-oxo-1-thia-4, 8-diazaspiro [4, 5] decane derivatives (V) were prepared from the corresponding 8-alkoxycarbonyl derivatives (IIb, c) by the Method A (HBr-AcOH), method B1 (KOH-iso-PrOH), or method B2 (Claisen's alkali). V were also prepared by the reaction of 4-piperidone hydrochloride (VIII) with corresponding mercapto acids and primary amines (method C). Sulfoxides (VI) of V were prepared by method A or method D1 (oxidation of V with H2O2), and sulfones (VII) were prepared by method A or method D2 (oxidation of V with KMnO4). VI and VII were not obtained by the method B1 or B2. 4-Oxo-1-thia-5, 9-diazaspiro [5, 5] undecane (V-35) was prepared by method A or method C, and the sulfone (VII-25) of V-35 was prepared by method A.
Dissolution of aluminosilicates in weak hydrochloric acid solution was studied. In general, sodium ions were at first dissolved into the solution, and then aluminum ions began to dissolve after the dissolution of sodium ions was almost completed. The amount of sodium and aluminum ions dissolved was just equivalent to the amount of acid consumed. In the course of dissolution of both ions, dissolution of silicon was also observed. From these facts, it was suggested that silicon atoms were dissolved as the result of breaking of aluminosilicate structure, in contrast with the case of sodium and aluminum ions. Therefore, the dissolution of silicon atoms was due to a secondary effect. One silicon atom dissolved when 1.3 aluminum atoms dissolved in the case of sodium aluminosilicates No.1-6, which were synthesized in alkaline medium, while one silicon atom dissolved when 2.7 aluminum atoms dissolved in the case of No.7 and 8, which were synthesized in acid medium. It was therefore concluded that the samples synthesized in acid medium were neither sodium aluminosilicates nor sodium aluminum silicates but sodium aluminum aluminosilicates. It was also found that the degree of crystallization and adsorption volume of N2 gas on crystalline aluminosilicates decreased when these crystals were washed with acid solution.
The compounds produced by the action of propyl or isopropyl chloride with guaiazulene had been comfirmed as the 3-substituted derivatives of guaiazulene from the visible region and nuclear magnetic resonance spectra. In the reaction with iso-propyl chloride, only one product (I) was obtained, but two products were produced from the reaction with propyl chloride. One of the two latter products was identified with I from retention time and mixed melting point test of the trinitrobenzoate. I and the other (II) were separated from the latter products by gas chromatography and both compounds were examined by mass and nuclear magnetic resonance spectra. From these results, it was confirmed that I and II correspond respectively to 3-isopropyl- and 3-propyl-guaiazulene.
The reaction of methylene blue with M- and N-active sialoglycopeptides released from human erythrocytes by ficin treatment was spectrophotometrically studied. The results show that sialoglycopeptides interact with methylene blue to form sialoglycopeptide-methylene blue complexes which give absorption peaks at 665 and 618 mμ, and the fact suggests that the interaction between sialoglycopeptides and methylene blue is an ionic bond reaction. The bound sialic acids of sialoglycopeptides may be the receptor site for methylene blue.
The metabolic fate of 14C-Metaproterenol [1-(3, 5-dihydroxyphenyl)-2-isopropylaminoethanol] was investigated by its oral administration to rabbits, rats, and mice. In all cases the radioactivity was found more in feces than in urine. On the other hand, a negligible amount of radioactivity was found in bile of the rabbit and in expiratory air of the mouse. Examination on the urinary metabolites by ion exchange chromatography denied the glucuronide formation of this drug in rabbits, although it suggested the production of acidic or neutral metabolites. These findings strongly suggested that absorption of this drug from gastrointestinal tract was rather poor and this might be one of the major reasons for much lower activity by oral than parenteral administration.
From the rhizome of domestic Menispermum dauricum DC., cheilanthifoline (I), stepholidine (III), and stepharine (VIII) were newly isolated, and also 6 kinds of yellow base (Base II to VII) in crystalline form.
Rhizomes of Dryopteris bissetiana C. CHR. (Aspidiaceae) were examined for phloroglucinol derivatives and margaspidin was isolated. This is the first time that margaspidin was isolated from Japanese ferns. Margaspidin was also detected by thin-layer chromatography from the rhizomes of D. pacifica TAGAWA, D. saxifraga H. ITO, and D. sacrosancta KOIDZ.