Chemiluminescences of cypridina luciferin in aprotic solvents and the structure necessary for the production of light is 3, 7-dihydroimidazo[1, 2-α]pyrazin-3-one. Chemiluminescence ability of 2-hydroxy-, 3-amino- and 3-hydroxy-imidazo[1, 2-α]pyridine derivatives, 3, 7-dihydroimidazo[1, 2-α]pyrazin-3-one derivatives, and 3-aminoimidazo[1, 2-α]pyrazine derivatives was tested in diglyme and in dimethyl sulfoxide solutions. Chemiluminescence of dihydroimidazopyrazinones is very much stronger than that of 3-hydroxyimidazopyridines and the amino derivatives produce almost no light. In the case of 6-(3-indolyl)-imidazopyrazinone derivatives the light yield is extremely enhanced by the addition of a trace of acetate buffer in the reaction mixture (Table II) ; the chemiluminescence light yiled of Cypridina luciferin(I), which has a 3-indolyl group at 6-position, is 0.06 which is ca. 15% of its bioluminescence light yield.
In order to examine the difference in biological fate of iron from iron hydroxide colloid for injection containing a variety of stabilizer, iron-dextran colloid labeled with 59Fe and 3H was injected intravenously into normal male mice and systemic distribution of 59Fe and 3H was examined. The result obtained was comparatively examined with that obtained by the injection of iron chondroitinsulfate colloid labeled with 59Fe and 3H, and the following observations were made. 1) The rate of disappearance of from blood and phagocytized in the reticuloendothelial cells depends on the kind of stabilizer used, and the rate of disappearance is faster in iron chondroitinsulfate than iron-dextran colloid. 2) Utilization of iron as hemoglobin iron and incorporated into red blood cells is not affected by the kind of stabilizer present. 3) Relative distribution of 3H and 59Fe in various organs is approximately the same from both kinds of colloid but some organs showed a difference considered to be due to the difference in the metabolism of stabilizer liberated after a long time.
1) Mass spectral measurements were made on diphenyl ether, diphenylamine, and their thiocyanates. It was found that the spectral data made it possible to know in which benzene ring the SCN group was present, and the position of SCN group was proved from nuclear magnetic resonance spectra. 2) Thiocyanation was examined by Huchel's approximation and the results obtained on the position of thiocyanation in the compounds of general [chemical formula] formula agreed approximately with experimental facts.
Edema-producing activity of 35 synthesized bradykinin fragments was tested by administration of 10 μg to a rat hind paw and the result was compared with that of 10 μg of bradykinin. All the peptides showed edematous activity, the strongest being bradykinin-(7-9)-tripeptide which produced edema of a degree comparable to that produced by bradykinin. Bradykinin-(1-8)-octapeptide and-(3-8)-hexapeptide also had a strong edema action. There did not seem to be a distinct correlation between the number and kind of amino acids constituting the peptide and edematous activity.
Radioactive compounds, N-iodo[131I]acetyl-dl-tryptophan (II), 3, 5-diiodo[131I]tyrosine (III), and p-iodo-(IV), m-iodo-(V), and o-iodo-pheny1alanine[131I](VI), were synthesized and used in experimental animals. In isotopic exchange reactions of IV, V, and VI, the reaction velocities largely depended upon specific activity of inorganic radioactive iodine-131 used. IV, V, and VI showed selective accumlation in pancreas of mice and rats, showing possibility of their use as pancreas scanning agents. In comparison with radioactive selenomethionine[75Se](I), IV showed higher pancreas/liver concentration ratio than I, when both were injected simultaneously into a mouse. Among three derivatives of iodo-phenylalanine, VI was demonstrated to give the highest pancreas/liver and pancreas/blood concentration ratios. It was also demonstrated that smaller administration dose of VI gave higher uptake into pancreas and liver. The accumulation of VI in pancreas was portrayed by autoradiogram of a mouse. It was found that this compound was also selectively taken into various kinds of tumor in rats and mice. However, the iodophenylalanine incorporated into pancreas or tumor was not utilized for protein synthesis, but remained in its original chemical form. In urine, a radioactive substance of another chemical form was found and its excretion rate was slower than that of original chemical form.
The amount of secondary alcohol in the reaction mixture of phenyl glycidyl ether (P.G.E.) with ethylmagnesium bromide is by several percent smaller than that of propylene oxide or phenylpropylene oxide. It comes to about 50% and increase in proportion to the number of carbon atoms in the Grignard reagents. Notable difference is not recognized between the reaction product of alkyl- or halogensubstituted P.G.E. with Grignard reagents and that of P.G.E. The reaction velocity of P.G.E. containing a nitro group with Grignard reagents is rapid and primary alcohol alone was obtained regardless of the number of carbon atoms in the Grignard reagents. Quantitative analysis of these reaction mixtures was carried out by gas chromatography. Thiophenol or o-chlorothiophenol was detected together with ordinary reaction products in the reaction mixture of phenyl thioglycidyl ether with Grignard reagents. On the other hand, the main reaction product of P.G.E. with ethyl bromoacetate in the presence of zinc dust is ethyl hydroxypentanoate and hydroxymethylbutanoate was not found.
Examination of Agastache formosanum HAY. growing in various parts of Japan proved they always contain l-isomenthone and l-pulegone as the characteristic constituents, contrary to methylchavicol in the case of A. rugosa O. KUNTZE. This fact reveals the distinct difference of these two allied species, both distributed in eastern Asia.
Antibacterial tests against Hiochi bacteria of Japanese Sake were made with 13 kinds of compounds which are derivatives of lichen components, including orsellinic acid esters, β-orcinolcarboxylic acid esters, and olivetonide. Butyl orsellinate showed about 4 times the antibacterial action of n-butyl p-hydroxybenzoate and about 8-16 times that of salicylic acid. Hexyl and octyl orsellinates showed a strong antibacterial activity, about 60 times that of butyl p-hydroxybenzoate and about 125-250 times that of salicylic acid. The antibacterial action of methyl β-orcinolcarboxylate was about 10 times that of butyl p-hydroxybenzoate and about 20-40 times that of salicylic acid, while that of its ethyl ester was about 20 times that of butyl p-hydroxybenzoate and about 40-80 times that of salicylic acid. Olivetonide also showed an antibacterial action, about 8 times that of butyl p-hydroxybenzoate and 15-30 times that of salicylic acid. This test has shown that these compounds all had a strong antibacterial action against Hiochi bacteria.
Lyofolic acid was reinvestigated by silica gel column chromatography and it was found to be contaminated with two minor components, one of which was identified as deacetyllyofolic acid. The molecular formula of lyofolic acid was revised as C38H62O11·2H2O. Alkaline hydrolysis of lyofolic acid gave a deacetylated compound, C36H60O10·3H2O, which was proved identical with one of the minor components. Hydrolysis of lyofolic acid with methanolic hydrogen chloride yielded lyofoligenic acid, C30H50O5, and glucose, and the signal of acetoxyl group disappeared in the nuclear magnetic resonance (NMR) spectrum of its aglycone. Genic acid contains one cyclopropane ring which has an isolated methylene group [chemical formula], two secondary and one tertiary alcohols, and one carboxylic acid group. Isopropylidene derivative was formed with acetone and p-toluenesulfonic acid between one secondary and one tertiary hydroxyl groups, [chemical formula].
In order to examine antiphlogistic-analgesic activity of indoline derivatives, 3-[ω-(N, N-dialkyl)aminoalkyl]-3-methyl-1-phenyl-(I) and 3-[ω-(N, N-dialkyl)aminoalkoxy]-3-methyl-1-phenyl-indolin-2-one (II), and their related compounds were synthesized. Among these, 28 compounds were tested for their inhibitory action on writhing syndrome produced by acetic acid, their effect on general behavior, and their acute toxicity.
Most of the fine powders used in pharmaceutical preparation are different in their cohesiveness and particle density from particulate solids in other industries, and it is assumed that the behavior of fine powder in the mixer differs from them. Very early stages of the progress of mixing were examined in the V-type mixer, using antipyrin and lactose powder screened into the fraction of -100/+150 mesh, and mixing ratio of 1 : 25. It has been observed that the circulating flows of a mass of particles exist in the V-type mixer and are independent of each shell in the case of such particulate solids as glass bead or Soma sand. This kind of flow was not observed in the present case when the active ingredient was charged to the bottom of mixer. Variation of concentration was traced at some places on the 1st and 2nd layers and results are shown in Fig.6(a)-(e). These peculiar trends auggest that the mixing process was just like 'diffusion' from the charging position of active ingredient. Another charging position (Fig.1) was employed to compare the mixing rate with this position.
It has been found that gelation takes place at 25° when guanosine, boric acid, and sodium hydroxide are mixed together. Results obtained from conductance and viscosity measurements indicated that a chelate of 2 : 1 molar ratio is formed between guanosine and the borate. This was supported also by the analytical data of the crystalline powder obtained from a mixture of guanosine, boric acid, and sodium hydroxide. The gel formation proceeded exothermically, and the chelate was more stable in weakly alkaline medium. Gelation of the guanosine-borate system was inhibited by the presence of urea. It was concluded that the network structure formed by hydrogen bonding between guanine moieties of adjacent chelate molecules is essential for gelation of the guanosine-borate-water system.
By the utilization of the marked reactivity of amines and diketene, α-acetamidoacyl derivatives of biologically active amines were synthesized in an attempt to decrease the toxicity of such amines. In this reaction (Chart 1), acetacetylated amines are submitted to the Schmidt reaction, and the compounds obtained are listed in Table I and II. It is desirable, in this reaction, to add sodium azide to the chloroform solution of the acetacylamide derivatives and then add conc. sulfuric acid dropwise, rather than its reverse of adding conc. sulfuric acid to the chloroform solution and then sodium azide. Otherwise, the Knorr reaction often occurs.
Preparative methods for 2-aminomethyl-1, 1-diphenyl-1-butene (I), a hypertensive drug, were investigated. The following three-step method was suggested to be the most suitable for the preparation of I. The first process is to obtain 2-cyano-1, 1-diphenyl-1-butanol (II) by condensation of butyronitrile and benzophenone in the presense of sodium hydride (molar ratio, 1 : 2 : 2) at 90°. The second is the reduction of II by sodium borohydride-CoCl2 system (molar ratio, II : NaBH4 : CoCl2=1 : 10 : 2) in MeOH at 20° to 2-aminomethyl-1, 1-diphenyl-1-butanol (III), and the final step is the dehydration of III to I in a mixture of acetic acid and conc. hydrochloric acid (20 : 1).
Leukopenia-inducing action of N-methyl-bis(3-mesyloxypropyl)amine hydrochloride (No.838) and bis(3-mesyloxypropyl)amine hydrochloride (No.864) was discussed. In spite of their similarity in chemical structure, the two compounds have different antitumor spectrum and different affinity to hematopoietic tissues. Leukopenia induced by No.838 was far more severe than that by No.864, which was found to be protected by 2-mercaptopropionylglycine to some extent without affecting its antitumor activity.
Pharmacological properties of 1-phenyl-4-guanylpiperazine (PGP) sulfate (I) were examined on various organs innervated by the sympathetic nerve. Effect of PGP derivatives on the acute toxicity of tyramine in mice was also examined with 1-phenyl-(I-PGP), 1-(3-chlorophenyl)-(II), 1-(4-chlorophenyl)-(III), 1-(3-methylphenyl)-(IV), and 1-(4-methylphenyl)-4-guanylpiperazine sulfate (V). The results may be summarized as follows : 1) PGP causes a rise in blood pressure and contraction of the nictitating membrane in spinal cats. These actions are blocked by phentolamine and by pretreatment with reserpine. PGP derivatives potentiate the pressor response induced by tyramine. 2) PGP shows positive inotropic and chronotropic actions on openchest dogs and isolated heart of guinea pigs, but these actions are blocked by DCI and pretreatment with reserpine and guanethidine. 3) PGP causes vasoconstriction on isolated rabbit ear. 4) PGP derivatives increase the acute toxicity of tyramine. There is a correlation between the potentiating action of PGP derivatives on the pressor response of tyramine and their ability to increase the toxicity of tyramine. 5) The sympathomimetic action of PGP might be classified as indirectly acting on the sympathetic nervous system.
The hydrolysis rate constants of acetylsalicylic acid in water mixed with ethanol, propylene glycol, or N, N-dimethylacetamide were determined at various concentrations (30-90%, v/v) at pH regions between 6 and 13 (pH values being obtained from direct measurement by glass electrode). It was assumed that, in these solvent systems, hydrolysis of acetylsalicylic acid is due to the decomposition of its anion from the degree of dissociation determined by ultraviolet (UV) absorption spectra. The pH-independent region of decomposition rate constant, as is known at pH 5-8 in aqueous solution, was found at pH higher than 8 in these binary systems. The increase in decomposition rate constants of acetylsalicylic acid in ethanol and propylene glycol with the concentration of organic solvents can be explained from the scheme of cyclic intermediate of acetylsalicylic acid by Garrett. However, in the case of higher concentration of N, N-dimethylacetamide, the rate constants at pH 6 decreased with concentration of the solvent, while increased the rate constants at pH higher than 7 could not be explained from this study.
Condensation of aldehydes (Va, b) with ethyl methyl ketone gave α, β-unsaturated ketones (VIa, b), which were reacted with ethyl cyanoacetate in the presence of ammonium acetate to afford the pyridone derivatives (VIIa, b), one of which (VIIb) was converted to 5, 6-dimethylpyridine derivatives (VIIIc, d). On the other hand, the compound (XI) was oxidized with selenium dioxide to afford 2-formylpyridine derivative (XIII).
In connection with previous reported antifungal substance, 11-iodo-10-undecynoic acid and its derivatives, 2) further a number of ω-iodo-acetylenic fatty acid derivatives were synthesized. It was found that these compounds had high antifungal activities in vitro.
The reaction of mercaptans with L-α-tosylamido-β-propiolactone (I) derived from L-asparagine was investigated. In the presence of one molar equivalent of alkali, I reacted with mercaptans to afford N-tosyl-L-serine (III) or methyl ester (IV) of III in aqueous THF solution or methanolic solution, respectively. However, by adding catalytic amount of alkali, L-α-tosylamido-β-hydroxypropionic acid thioester (V) was obtained from the reaction mixture of I and mercaptans in THF or aqueous THF solution. No reaction was observed when I was treated with mercaptans in the presence or absence of acid catalyst.