Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Volume 36, Issue 10
Displaying 1-50 of 74 articles from this issue
  • YOSHIO SASAKI, TATSUYA TAKAGI, HIDEKO KAWAKI
    1988 Volume 36 Issue 10 Pages 3743-3752
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    From the evaluation, of the force constant derived from the modified Lennard-Jones 12, 6 potential, the substituent entropy constant σs° has been deduced and revealed to be an effective descriptor representing both attractive (in other words, dispersion) and repulsive forces. Furthermore, for polar molecules, an additional descriptor 2 /α was proved to be a reasonable one representing both induction and orientation forces. These two kinds of quantitative structure -activity relationships (QSAR) descriptors are applied to many substituted methane and benzene derivatives and shown to be useful.
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  • BUNJI UNO, NAOKI KAIDA, TOSHIO KAWAKITA, KENJI KANO, TANEKAZU KUBOTA
    1988 Volume 36 Issue 10 Pages 3753-3759
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Electronic spectra of aromatic amine N-oxides show a marked blue shift with the change of solvent polarity from aprotic solvents to protic ones. This is very useful to examine the hydrophobic interaction between the amine N-oxides and cyclodextrins (CyD) in water. Among the various systems studied a typical example is the system of 4-nitroquinoline N-oxide (4NQO) and 2, 6-di-Omethyl-β-cyclodextrin in water. A clear red shift of the ultraviolet (UV) spectrum of 4NQO was observed upon inclusion complex formation, indicating directly that the CyD cage environment is much more hydrophobic than in water. Thermodynamic and spectroscopic constants pertinent to those inclusion complex formations were evaluated and the results are discussed in relation to the complex formation mechanisms.
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  • YOSHINOBU MUROFUSHI, MISAKO KIMURA, HARUMITSU KUWANO, YASUTERU IIJIMA, ...
    1988 Volume 36 Issue 10 Pages 3760-3769
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Addition reactions of the C4'-C5' double bond of griseolic acid were investigated. C4'-C5' Dihydrogriseolic acid was obtained by reduction of the adduct having halogen at the 4'-position. The ring juncture of the two five-membered rings of the C4'-C5' dihydro derivatives was of all- “cis” configuration. Acetolysis of the protected dihydrogriseolic acid gave the corresponding 1'-acetoxy sugar derivative. Reaction of this sugar derivative with silylated bases gave guanine and uracil derivatives of the dihydrogriseolic acid. The cyclic nucleotide phosphodiesterase (PDE)-inhibitory activity of the C4'-C5' cis dihydrogriseolic acid derivative was weaker than that of griseolic acid. The uracil derivative of C4'-C5' cis dihydrogriseolic acid completely lost the inhibitory activity against both adenosine 3', 5'-cyclic monophosphate (cAMP) and guanosine 3', 5'-cyclic monophosphate (cGMP) PDE, whereas the guanine derivative showed reduced inhibitory activity against cAMP PDE, but retained its activity against cGMP PDE. It was also apparent that the C4'-C5' trans dihydro derivative which was obtained as a minor product from the same culture broth of griseolic acid had almost the same inhibitory activity as griseolic acid.
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  • HARUKO TAKECHI, MINORU MACHIDA, YUICHI KANAOKA
    1988 Volume 36 Issue 10 Pages 3770-3779
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Upon irradiation of N-methylphthalimide (1) in the presence of N-acylindole derivatives (2 or 11), [2+2] cycloaddition occurred to give sterically hindered oxetanes (5) in moderate yields. Some reactions of these imide-oxetanes, such as formation of benzoxazepines (8 and 12) and eightmembered lactams (9 and 10), are also described.
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  • MASARU KOBAYASHI, TAKUYA HAMAGUCHI
    1988 Volume 36 Issue 10 Pages 3780-3786
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Six new cembranoid diterpenes, sinulariols C and D (1 and 2a), sinularial A (3), sinularic acid A (4), and sinularones A and B (5 and 6) were isolated from the lipid extract of the soft coral Sinularia mayi, together with four known compounds. The structures of the new compounds were elucidated by means of spectroscopic analyses, Horeau determination, and chemical conversion. Sinulariol C (1) was found to be an C-14 isomer of “13-hydroxyneocembrene” (8a) and gave sinularone A (5) on oxidation. Sinularial A (3) is the first example of a cembranoid aldehyde isolated from marine sources. Compounds 1 to 4 are plausible precursors to the cembranoid lactones found in various soft corals.
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  • YUTAKA OKADA, TOYONORI TAKEBAYASHI
    1988 Volume 36 Issue 10 Pages 3787-3792
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Optically active crystals of 10-bromo-11b-(2-fluorophenyl)-2, 3, 7, 11b-tetrahydrooxazolo-[3, 2-d][1, 4] benzodiazepin-6 (5H)-one were obtained by preferential crystallization; they were sometimes levorotatory and sometimes dextrorotatory. This phenomenon was proved to be an example of second-order asymmetric transformation between enantiomers. The rapid racemization reaction, which was essential for asymmetric transformation, was observed in methanol. The decrease of optical rotation obeyed good pseudo first-order kinetics and the half-lives of the racemization in methanol were estimated to be about 21 s at 30°C, 37s at 20°C and 70s at 10°C. The mechanism and factors which affect the rate of the racemization are discussed.
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  • TERUYO MATSUMOTO, MASAKO OHSAKI, KAORU YAMADA, FUYUHIKO MATSUDA, SHIRO ...
    1988 Volume 36 Issue 10 Pages 3793-3804
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    The 14-fluoroanthracyclines (5-10) carrying L-daunosamine, D-2-deoxyribose, or L-2-deoxyfucose as their glycosidic sugar moieties, were synthesized starting from (-)-7-deoxy-4-demethoxydaunomycinone ((R)-11a) or (-)-7-deoxydaunomycinone ((R)-11b). As key steps, the synthetic route features a novel fluorination reaction in which tetrabutylammonium fluoride is employed in the presence of a half equivalent of p-toluenesulfonic acid, and the previously explored glycosidation reaction in which trimethylsilyl trifluoromethanesulfonate is utilized as an activating reagent. In P388 in vivo tests, 5, 6, 9, and 10 exhibited prominent cytotoxicity comparable with that of adriamycin (1). Notable antitumor activity was also observed for 6 and 9 in P388 in vivo tests.
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  • CHIHIRO ITO, MIYUKI MATSUOKA, TOYOKO MIZUNO, KAKO SATO, YOKO KIMURA, M ...
    1988 Volume 36 Issue 10 Pages 3805-3810
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Six new coumarins, 6-formylumbelliferone (1), hassanon (2), 5-hydroxyseselin (4), cis-grandmarin (6, cis), trans-grandmarin isovalerate (8, trans), and kinocoumarin (9), were isolated from roots and root barks of some Citrus plants, and their structures were determined by means of spectral and chemical studies.
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  • FUMIKO ABE, YUJIRO MORI, Tatsuo YAMAUCHI, YASUHISA SAIKI
    1988 Volume 36 Issue 10 Pages 3811-3815
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Five new strophanthidin glycosides, strophanthidin glucos-3-ulosyl-cymaroside, glucosyldigitalosyl-cymaroside, cellobiosyl-cymaroside, digitaloside, and glucosyl-digitaloside, were obtained from the roots of Apocynum venetum L. var. basikurumon HARA, along with free strophanthidin and the common glycosides in Apocynum species, cymarin and k-strophanthidin-β Strophanthidin glucoside was also obtained.
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  • MIKIO HORI, TADASHI KATAOKA, HIROSHI SHIMIZU, HARUMI AOKI
    1988 Volume 36 Issue 10 Pages 3816-3825
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Treatment of 1-methyl-4-phenyl-1-thio-2H-chromenium perchlorate (2) with sodium hydride yielded a dimeric compound 4 and two rearrangement products 5 and 6 via unstable 1-methy1-4-phenyl-l-thianaphthalene (3). On heating with potassium hydroxide in ethanol, 1-methy1-2, 4-dipheny1-1-thio-2H-chromenium perchlorate (9) gave a dimeric compound 13 and two ring-opened products 11a and 12a, but no rearrangement product. On the other hand, 2-cyano-l-methy1-4-phenyl-1-thianaphthalene (20) prepared from the corresponding 1-thiochromenium salt 19 by treatment with triethylamine in ethanol was quite stable, and it is the first example of a stable and crystalline 1-thianaphthalene.
    Reactions of the 1-thianaphthalene 20 with electrophiles such as tetracyanoethylene, maleic anhydride, and 4-phenyl-1-thianaphthylium perchlorate gave the dimeric compound 23. However, the treatment of 20 with dimethyl acetylenedicarboxylate yielded a new ring expansion product 27 having a sulfur-containing nine-membered ring.
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  • HARUKI SASHIDA, MASANOBU KATO, TAKASHI TSUCHIYA
    1988 Volume 36 Issue 10 Pages 3826-3832
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Treatment of 6-unsubstituted 2-ethynyl-1-phenacylpyridinium bromides (10a-c) with 1, 5-diazabicyclo [5.4.0] undec-5-ene in refluxing benzene resulted in cyclization to give the 3-benzoylindolizines (11) via the N-ylide intermediates 13, whereas heating the salts 10 in refluxing acetic acid afforded the 1-benzoylindolizines (12). Upon similar treatment with the base, 2-ethynyl-6-methylpyridinium salts (20a-c) gave the 3-benzoyl-5-methylindolizines (22); in the case of the phenylacetylene compound 20c, 2, 3-diphenylcycl [3.2.2] azine (23) was also obtained. However, the reaction of 6-amino-2-ethynylpyridines (27a-c) with phenacyl bromide produced 5-ethynyl-1-azaindolizines (28), which were converted into 1-azacycl [3.2.2] azines (29). The mechanisms of these intramolecular cyclizations are discussed.
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  • HITOSHI TANAKA, MASAYA ISHIHARA, KAZUHIKO ICHINO, KAZUO ITO
    1988 Volume 36 Issue 10 Pages 3833-3837
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    The reaction of 8-hydroxy-6-methoxy-7-methoxymethoxycoumarin (3) with ethyl 2-bromo-3-(4-benzyloxy-3, 5-dimethoxypheny1)-3-oxopropionate (5) in the presence of potassium tert-butoxide gave the condensation product (6), which, on treatment with hydrochloric acid followed by reduction with lithium borohydride, was converted into a diastereomeric mixture of alcohols (8a, b). Treatment of the alcohols (8a, b) with 35% hydrochloric acid in acetic acid furnished aquillochin (cleomiscosin C)(1). The regioisomer cleomiscosin D (2) was similarly synthesized from 10.
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  • AKIO OHSAWA, TERUMITSU KAIHOH, TAKASHI ITOH, MAMIKO OKADA, CHIKAKO KAW ...
    1988 Volume 36 Issue 10 Pages 3838-3848
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Reactions of N-aminopyrazoles with halogenating reagents (Cl2, Br2, I2, BrCl, ICl, IBr, N-chlorosuccinimide, and N-bromosuccinimide) were examined. Some of these reagents preferentially lead to oxidation of the amino group to give the corresponding 1, 2, 3-triazines as major products, while others mainly gave either or both of 1-amino-4-halopyrazoles and 5-halo-1, 2, 3-triazines as the result of halogenation of the 4-position of the pyrazole ring prior to the oxidation of the amino group. In some cases, the oxidation of the amino group and the halogenation of the pyrazole ring proceeded concurrently to form not only the unhalogenated triazines but also the l -amino-4-halopyrazoles and the 5-halotriazines. Various reagents and reaction conditions were explored to utilize the reaction for the synthesis of halogenated and unhalogenated 1, 2, 3-triazines.
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  • TSUTOMU HATANO, TAKASHI YOSHIDA, TETSURO SHINGU, TAKUO OKUDA
    1988 Volume 36 Issue 10 Pages 3849-3856
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy was utilized for the assignments of the glucose carbon signals in the 13C-NMR spectra of hydrolyzable tannins in which the glucopyranose core takes a 1C4 or related boat conformation, and of tannins possessing a Cglucosidic linkage. Remarkable changes in the sequences of glucose carbons were observed with change in the conformation of the glucose core, and with the formation of a C-glucosidic linkage. The chemical shifts of the C-2 signals of the glucose cores adopting the open-chain form in Cglucosidic tannins and in complex tannins can be utilized for the discrimination of the configurations at C-1 in these tannins.
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  • MIKA HATANO, SUSUMU FUNAKOSHI, NOBUTAKA FUJII, MASAHARU TAKEYAMA, MITS ...
    1988 Volume 36 Issue 10 Pages 3857-3866
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    A 28-residue peptide corresponding to the entire amino acid sequence of vasoactive intestinal polypeptide of guinea pig origin (gVIP) was synthesized by assembling 6 peptide fragments, followed by thioanisole-mediated deprotection with 1 M trimethylsilyl trifluoromethanesulfonate in trifluoroacetic acid. The synthetic peptide was biologically as active as synthetic porcine VIP, but behaved immunologically in a different manner from the above mammalian VIP.
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  • NOBUYA KATAGIRI, TORU HANEDA, NOBUHISA WATANABE, ETSUKO HAYASAKA, CHIK ...
    1988 Volume 36 Issue 10 Pages 3867-3877
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Asymmetric synthesis of [1S, 2S, 3R, 4R]-2, 3-dihydroxy-4-hydroxymethylcyclopent-1-ylmalonate (its racemic form is already known as a versatile building block for carbocyclic C-nucleosides) was achieved by Diels-Alder reaction of cyclopentadiene with di-l-menthyl acetoxymethylenemalonate, followed by retrograde aldol C-C bond fission under reductive conditions. Asymmetric induction in Diels-Alder reactions using the chiral dienophile and its nor-acetoxy derivative is discussed from a mechanistic viewpoint and a new concept for asymmetric induction is proposed.
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  • TAIKO ODA, YUMIKO SUEYOSHI, KAORUKO HIROTA, YOSHIHIRO SATO
    1988 Volume 36 Issue 10 Pages 3878-3886
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    The enzymatic hydrogenation of 5'-formylgriseofulvin (3a) with a cell-free system of Streptomyces cinereocrocatus afforded 5'α-hydroxymethylgriseofulvin (4a). The structure of 4a was determined by comparison of the proton nuclear magnetic resonance (1H-NMR) spectrum, mass spectrum (MS), circular dichroism (CD) and ultraviolet (UV) spectrum with those of 5'α- and 5'β-hydroxymethylgriseofulvin (4a and 5a) which were synthesized chemically. The stereochemistry of hydrogenation was unequivocally determined by 270 MHz 1H-NMR analysis of the acetonide (10b) which was derived from the product obtained by the enzymatic conversion of [7'-2H] 5'-formylgriseofulvin (3b)(Chart 3). The results clearly indicated that the 7'-pro-S-hydrogen of 4a originates from the 7'-hydrogen atom of the substrate (3a), and it was further proved that the 5'-βhydrogen of 4a originates from the medium by the use of deuterium oxide.
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  • TOSHIO KINOSHITA, NORIKO NAKAHATA, AKIKO KOUCHI, SUNAO FURUKAW
    1988 Volume 36 Issue 10 Pages 3887-3896
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    The reaction of 1-(2-hydroxyethyl and 2-hydroxypropy1)-3, 6-dimethyl-2, 4 (1H, 3H)-pyrimidinedione (2 and 3) with bromine afforded 5-bromo-6-bromomethyl-l-(2-bromoethyl and 2-bromopropy1)-(4 and 5), 5-bromo-1-(2-bromoethyl)-6-dibromomethy1-2, 4 (1H, 3H)-pyrimidinedione (6), and 8, 8-dibromo-6, 8a-dimethyl (or 2, 6, 8a-trimethyl)-5, 7-dioxoperhydrooxazolo [3, 2-c] pyrimidine (8 or 9).
    Compound 4 reacted with sodium methoxide to give the 5-debrominated compounds 10, 11, and 13 [1-(2-bromoethyl)-, 1-vinyl-, and 1-(2-hydroxyethyl)-6-bismethoxy) methy1-3-methy1-2, 4-(1H, 3H)-pyrimidinedione]. Treatment of 4 with sodium dithiocarbamate and potassium thiolacetate gave 1 [2-(N, N-dimethylthiocarbamoylthio) ethy1]-6-(N, N-dimethylthiocarbamoylthiomethy1)-and 1-(2-acetylthioethyl)-6-acetylthiomethy1-5-bromo-3-methy1-2, 4 (1H, 3H)-pyrimidinedione (14 and 15).
    The reaction of 4 with sodium benzenesulfinate yielded 5-bromo-1-(2-bromoethyl)-3-methy1-6-benzenesulfonylmethy1-2, 4 (1H, 3H)-pyrimidinedione or 4-bromo-2-methy1-5-benzenesulfonyl-1, 3 (2H, 8H)-dioxoperhydropyrrolo [1, 2-c] pyrimidine (19 or 21).
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  • YASUMITSU TAMURA, SHUJI AKAI, HISAKAZU KISHIMOTO, MANABU SASHO, MASAYU ...
    1988 Volume 36 Issue 10 Pages 3897-3914
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Practical total synthesis of 11-deoxyanthracyclinones (8 and 9) was accomplished on the basis of two effective syntheses of the key intermediates (14 and 15) and the subsequent highly stereoselective introduction of a C-7 cis-hydroxyl group. Glycosidation of 8 with a suitably protected L-daunosamine (37) followed by deprotection provided 4-demethoxy-11-deoxydaunomycin (5). The C-13 acetal derivative (34) of 9 was successfully employed for the glycosidation to achieve the first total synthesis of 11-deoxydaunomycin (6). Two novel synthetic 11-deoxyanthracyclines (10 and 11) possessing a neutral sugar instead of L-daunosamine were also synthesized.
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  • KIYOSHI SAKINA, KEIKO KAWAZURA, KAZUYUKI MORIHARA, HARUAKI YAJIMA
    1988 Volume 36 Issue 10 Pages 3915-3919
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Cholecystokinin-octapeptide was synthesized by enzymatic condensations of three fragments, without side-chain protection, except for Tyr. Fmoc-Asp-Tyr (SO3Ba1/2)-OH, prepared by the concerted action of proteases, followed by pyridinium trifluoroacetylsulfate treatment, was used as the N-terminal fragment. In the final step, the Nα-Fmoc group employed as a sole protecting group was easily removed by base treatment without affecting the SO3 moiety.
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  • TSUTOMU HATANO, REIKO KIRA, TAEKO YASUHARA, TAKUO OKUDA
    1988 Volume 36 Issue 10 Pages 3920-3927
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    A new dimeric hydrolyzable tannin named isorugosin D (11), and two new monomeric tannins of related structures, isorugosin A (10) and isorugosin B (1), were isolated from the leaf of Liquidambar formosana HANCE (Hamamelidaceae). The orientation of the valoneoyl group at 0-4 and 0-6 of the glucose core in isorugosins A, B and D was found to be different from that of rugosin A (7), rugosin B (6) and rugosin D (18), and the orientations of this group in the tannins of both type were confirmed on the basis of the two-dimensional nuclear magnetic resonance spectrum (long-range 1H-13C correlation spectrum) of rugosin A (7).
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  • JUN'ICHI KATAKAWA, HIDEAKI YOSHIMATSU, MORIHIRO YOSHIDA, YONG ZHANG, H ...
    1988 Volume 36 Issue 10 Pages 3928-3932
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Synthesis of the alkaloids, (±)-cherylline (1) and (±)-latifine (2), was accomplished by application of an isocyanate cyclization reaction according to Tsuda's two step procedure for constructing 1, 2, 3, 4-tetrahydroisoquinol-l-one and a regioselective cleavage reaction of aromatic methyl ethers with dimethyl sulfide in methanesulfonic acid.
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  • SYLVIANE GIORGI-RENAULT, JEAN RENAULT, MICHEL BARON, PATRICIA GEBEL-SE ...
    1988 Volume 36 Issue 10 Pages 3933-3947
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    With the aim of obtaining new antitumor drugs more active than previously described 5, 8-quinazolinediones, a series of dimers of 5, 8-quinazolinediones linked in the 4-position by a simple or a substituted χ, ω-diaminopolymethylenic chain was studied. The structure-activity relationships of these compounds are discussed as functions of the length of the chain, presence or absence of other functional groups, nature of these functional groups, position of the chain and nature of the substituents in the 6 and (or) 7-positions. When bis (5, 8-quinazolinediones) were substituted in the 6-position with a methoxyl group, the dimerization showed a variable effect on cytotoxicity toward L 1210 leukemia cells. Bis [4-amino-bis-6, 7 (1-aziridinyl)-5, 8-quinazolinediones] which exhibited high cytotoxic activity (IC50 0.0037 to 0.018μm) were further screened in vivo for activity against murine P388 leukemia. Antitumor activity was increased by the dimerization of the molecule. The most potent compound bears an additional tertiary amino function on the chain.
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  • HIROSHI OHTAKA, KENJI YOSHIDA, KENJI SUZUKI, KOICHI SHIMOHARA, SHIGERU ...
    1988 Volume 36 Issue 10 Pages 3948-3954
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    From a search for antiulcer agents with cytoprotective activity by random screening, 1-(pyrrolidinocarbonylmethyl)-4-(2, 3, 4-trimethoxybenzyl) piperazine dimaleate (4h) was found as a lead compound. Analogues of 4h were synthesized and evaluated for antiulcer activity as well as toxicity. Four compounds (4h, p, w, x) exhibited potent antiulcer activity in several gastric ulcer models and low toxicity without any antisecretory activity. The antiulcer activity of these compounds was considered to be based on the cytoprotective activity.
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  • HIROSHI OHTAKA, KENJI YOSHIDA, KENJI SUZUKI
    1988 Volume 36 Issue 10 Pages 3955-3960
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Quantitative structure-antiulcer activity relationships of 1-(aminocarbonylalkyl)-4-benzylpiperazine derivatives (I) were analyzed by using the adaptive least-squares (ALS) technique. Discriminant functions show that (1) a bulky amide moiety is disadvantageous, (2) a small number of methylene groups between carbonyl and piperazine is favorable, (3) a substituent which has a large B1 value (or B2 value when the substituent is forced to be in the in-plane conformation) with low lipophilicity at the 3 and/or 4 position of the benzyl moiety is favorable for antiulcer activity with low acute toxicity.
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  • KOJI IUCHI, MASAHIRO NITTA, KEIZO ITO, KOICHI SHIMOHARA, GORO TSUKAMOT
    1988 Volume 36 Issue 10 Pages 3961-3966
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Several N-acyl di-or tripeptides related to proglumide (PhCO-DL-Glu-NPr2) were prepared and their effects on gastric secretion were examined by intraperitoneal injection in rats. PhCOGlu (Phe-NH2)-NPr2, Z-Glu (Phe-NH2)-NPr2, PhCO-Glu (NPr2)-Phe-NH2 and PhCO-Asp-(Phe-NH2)-NPr2 inhibited gastric secretion, while PhCO-Glu (Asp-Phe-NH2)-NPr2 stimulated gastric secretion. Of these peptides, PhCO-Glu (Phe-NH2)-NPr2 showed the most potent inhibitory activity against gastric secretion, and was more potent than proglumide.
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  • MINEO SHIMIZU, HIDEKI TSUJI, HISASHI SHOGAWA, HIDEKI FUKUMURA, SEIICHI ...
    1988 Volume 36 Issue 10 Pages 3967-3973
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    The ether-soluble fraction of MeOH extract from the leaves of Cryptomeria japonica D. DON showed an anti-inflammatory effect when topically applied to rats and an inhibitory effect on histamine-induced ileum contraction. The active component was isolated and identified as ciscommunic acid (1). Two new diterpenoids were also isolated along with two known compounds and were determined to be imbricataloic acid dimethyl acetal (5) and (E)-13-hydroxylabda-8 (17), 11, 14-trien-19-oic acid, obtained as the methyl ester (6m), by chemical and spectroscopic methods.
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  • YUKINOBU IKEYA, HIROTOSHI KANATANI, MISAKO HAKOZAKI, HEIHACHIRO TAGUCH ...
    1988 Volume 36 Issue 10 Pages 3974-3979
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Two new dibenzocyclooctadiene lignans, gomisin S (1) and gomisin T (2), were isolated from the fruits of Schizandra chinensis BAILL.(Schizandraceae). On the basis of spectral methods and chemical transformations, the structures of 1 and 2 were elucidated as (6S, 7S, 8S, S-biar)-5, 6, 7, 8-tetrahydro-1, 2, 10, 11, 12-pentamethoxy-6, 7-dimethy1-3, 8-dibenzo [a, c] cyclooctenediol and (6S, 7S, R-biar)-5, 6, 7, 8-tetrahydro-1, 2, 10, 11, 12-pentamethoxy-6, 7-dimethy1-3, 7-dibenzo [a, c] cyclooctenediol, respectively.
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  • SUSUMU TIANAKA, MICHIO TAKIDO
    1988 Volume 36 Issue 10 Pages 3980-3984
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Two new naphthopyrones, cassiasides B (1) and C (2), were isolated from the seeds of Cassia obtusifolia L. along with rubrofusarin 6-O-gentiobioside. The structures of the two new compounds 1 and 2 were established as rubrofusarin 6-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside and toralactone 9-O-β-gentiobioside, respectively, on the basis of spectral and chemical evidence.
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  • OSAMU FUJISHITA, MASAAKI HIRAKAWA, KAZUHIRO NAKASHIMA, SHUN HIGUCHI, K ...
    1988 Volume 36 Issue 10 Pages 3985-3993
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    The determination of the molecular volumes of organic substances for which values of specific gravity (d) are not available was investigated. The values of van der Waals volume (VA3/molecule) for aliphatic saturated monocarboxylic acids are closer to those of molecular weight per specific gravity (M/d: cm3/mol) than those of Vw (cm3/mol). The slope of the correlative equation between VA and M/d for organic anionic substances is 1.03, but that between Vw and M/d is 0.62.
    The values of VA for organic anionic substances show a good correlation with the absolute ionic mobility (mo) as well as M/d. The values of VA for amino acids and dipeptides also showed a better correlation with mo than the molecular weight (M). Thus, the values of mobility could be better estimated from the molecular volume than the molecular weight.
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  • TERUAKI AKAO, HIRONORI TAMEI, KYOICHI KOBASHI
    1988 Volume 36 Issue 10 Pages 3994-3999
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Neither the supernatant nor the precipitate fraction obtained from sonicated streptococci produced streptolysin S, but the combination of both fractions restored the ability to produce streptolysin S. Streptolysin S production by the precipitate required heat-stable and low-molecular substance (s) in the supernatant in addition to maltose and carrier (s) such as ribonuclease resistant yeast ribonucleic acid. The heat-stable factor could be replaced by brain heart infusion (BHI) broth. Moreover, proteose peptone involved in BHI and protease digests of proteins such as bovine serum albumin (BSA) and casein showed stimulative effects on streptolysin S production, but BSA, casein, casamino acids and an amino acid mixture did not. Some peptides having molecular weights of several thousands were required for streptolysin S production by the precipitate.
    These peptides could not be replaced by carriers and maltose for hemolysin production by the precipitate. Thus, three inducer factors, carrier, maltose and peptides, were required for streptolysin S formation. Peptides and maltose were essential for streptolysin S production in the cells, but not for release of the hemolysin from the cells into the medium, which required the carrier.
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  • TOMOKO NASHIDA, TOMOKO ITOH, TAKAYUKI SHIRAISHI, YUTAKA UDA
    1988 Volume 36 Issue 10 Pages 4000-4007
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    The substrate specificities of the squid liver α-N-acetylgalactosaminidases I and II were studied with natural compounds containing α-N-acetylgalactosaminyl or other glycosyl terminals as substrates. Both α-N-acetylgalactosaminidases I and II hydrolyzed terminal α-N-acetyl-galactosaminyl linkages of the natural compounds investigated; asialo bovine submaxillary mucin, Forssman glycolipid, human ovarian cyst A-glycoprotein and blood group A-type ghosts. On the other hand, the oligosaccharides containing α-galactosyl terminals, ceramide trihexoside and human ovarian cyst B-glycoprotein, were hydrolyzed by α-N-acetylgalactosaminidase I but not by α-N-acetylgalactosaminidase II. The milk oligosaccharides with other glycosyl terminals were nxot hydrolyzed by either enzyme. Application of α-N-acetylgalactosaminidase from squid liver together with other glycosidases was effective in structural studies of Forssman glycolipid.
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  • TAKAYUKI NAGAI, HARUKI YAMADA
    1988 Volume 36 Issue 10 Pages 4008-4018
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Sialidase activity was detected in mouse liver, and was localized predominantly in the lysosomal fraction. Weak activity was also contained in the microsomal fraction, but little was detected in the cytosolic fraction. The optimum pH values of these sialidase activities were 4.0-4.5 for 4-methylumbelliferyl-α-D-N-acetylneuraminate (4-M U-NeuAc) and sialyllactose.
    The sialidase activity in the lysosomal fraction was very unstable, but was partially stabilized in the presence of phenylmethylsulfonyl fluoride, Ca2+, Mg2+, Mn2+ and Zn2+.
    The lysosomal and microsomal sialidase fractions were active preferentially toward ganglioside mixture, in the presence of sodium cholate as a detergent. These enzymes were also active toward all of the sialooligosaccharides and sialoglycoproteins tested. Those substrates possessing an α(2→3)-sialyl linkage were hydrolyzed much faster than those with an α(2→6) or α(2→8) sialyl linkage. These sialidase fractions were much more active toward glycopeptides than glycoproteins. The microsomal sialidase fraction was also active toward submaxillary mucin (bovine), suggesting that it is capable of hydrolyzing O-acetylated sialic acid residues.
    When the lysosomal fraction was disrupted hypotonically, the activity toward 4-MU-NeuAc and sialyllactose was mainly recovered in the 15000×g supernatant, and it was fractionated with ammonium sulfate. The fractionated soluble lysosomal sialidase failed to attack gangliosides, andwas only weakly active toward glycoproteins but was capable of hydrolyzing glycopeptides and oligosaccharides. This enzyme was further purified by chromatography on diethylaminoethyl (DEAE)-cellulose, concanavalin A adsorption, affinity chromatography on Sephadex G-200 and high performance liquid chromatography on coupled columns of TSK-GEL G5000PW and G4000PW. When the soluble lysosomal sialidase fraction was subjected to DEAE-cellulose chromatography, most of the β-galactosidase was eluted in the unadsorbed fraction, but the sialidase was eluted in the unadsorbed and the adsorbed fractions.
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  • YOSHIO TACHIBANA, TAKAHARU MIZUTANI
    1988 Volume 36 Issue 10 Pages 4019-4025
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Amino acid residues contained in the recognition sites of seryl-transfer ribonucleic acid (tRNA) synthetase (SerRS) were studied by chemical modification. Ser residues were modified with phenylmethanesulfonyl fluoride, and appeared to be unnecessary for the recognition. However, the modification of Arg residues with phenylglyoxal, His residues with diethylpyrocarbonate and sulfhydryl groups with 5, 5'-dithiobis (2-nitrobenzoic acid), N-ethylmaleimide, iodoacetic acid or iodoacetamide showed that these residues were essential for the tRNA recognition by SerRS. Protection experiments with substrates from inactivation of Ser-tRNA formation by modification suggested that Arg residues interact with the γ-phosphate of adenosine triphosphate and tRNA. Modification of sulfhydryl groups showed that the groups interact with the hydroxyl groups of ribose of the CCA-end on tRNA. Furthermore, in order to understand the recognition mechanism between SerRS and tRNAser, some kinetic parameters such as the Km and Vmax values of yeast tRNAser and E. coli tRNAser for bovine SerRS were compared with the values of bovine tRNAser.
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  • MAKOTO OTSUKA, NOBUYOSHI KANENIWA
    1988 Volume 36 Issue 10 Pages 4026-4032
    Published: October 25, 1988
    Released on J-STAGE: May 27, 2011
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    The crystallization process of noncrystalline indomethacin (IMC) obtained by the grinding and by the fusion method was analyzed by a kinetic method. The noncrystalline samples of IMC were the α form ground for 10 h at 4°C (GNCγ), the γ form ground for 10h at 4°C (GNCγ) and the fused solid (NC). Ten kinetic models were employed, and crystallinity was determined by X-ray diffractometry. Data obtained were used to determine the thermodynamic parameters and crystallization mechanism.
    Under isothermal conditions GNCγ crystallized in both the α and γ forms simultaneously. The GNCγ and NC crystallized in the γ form, and the results of the Hancock-Sharp method suggested that both crystallizations occurred by a two-dimensional phase boundary reaction; the activation energies (E) were estimated to be 24.1 and 27.2 kcal/mol. The crystallization rate of GNCγ was about 60 times faster than that of NC, and therefore NC was a very stable noncrystalline solid. These results suggest that there are several kinds of noncrystalline solids.
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  • SHOZO MIYAZAKI, HIDEKI YAMAGUCHI, CHIZUKO YOKOUCHI, MASAHIKO TAKADA, W ...
    1988 Volume 36 Issue 10 Pages 4033-4038
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    The release rate of indomethacin from chitosan granules was compared with that of conventional commercial indomethacin capsules and a sustained-release capsule. In contrast with the rapid release of a commercial conventional capsule form, sustained release from the chitosan granules was observed. Furthermore, the release rate could be controlled by changing the mixing ratio of drug and chitosan.
    The potential of chitosan granules as an oral sustained-release dosage form of indomethacin was investigated in rabbits. When a conventional commercial capsule was administered orally to rabbits, the plasma concentration reached the maximum level 1 h after administration. In the case of the granules with a 1: 2 mixture of drug and chitosan, the chitosan granules did not give a sharp peak of plasma concentration, but produced a sustained plateau level of indomethacin. The area under the plasma concentration curve (AUC)(0-8 h) value of chitosan granules showed a slightly higher value than that of commercial capsules. This may be due to the slow rate of release from the chitosan granules and the longer residence time in the stomach.
    Thus, in terms of decrease in the peak of plasma concentration and maintenance of indomethacin concentration in plasma, the chitosan granules were superior to the conventional commercial capsules. Indomethacin granule preparations using chitosan may be practically useful as oral preparations with reduced side effects and with prolonged action.
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  • YOSHINOBU NAKAI, KEIJI YAMAMOTO, KATSUHIDE TERADA, GAMAL A. EL-GENDY
    1988 Volume 36 Issue 10 Pages 4039-4044
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    The solid dispersion of naphthalene with heptakis-(2, 6-di-O-methyl)-β-cyclodextrin (DMCD) has been studied by using X-ray diffraction and thermal methods. The influence of the solid dispersion on the dissolution and sublimation of naphthalene were studied. X-Ray diffraction and thermal data indicated the amorphous state of naphthalene and DMCD. Enhanced dissolution and reduced sublimation characteristics were observed in the ground mixture and the coprecipitate. The sublimation rate of naphthalene from the ground mixture and the coprecipitate increased during storage at high relative humidity due to crystallization.
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  • KEN-ICHI SHIROTANI, ETSUKO SUZUKI, YUTAKA MORITA, KEIJI SEKIGUCHI
    1988 Volume 36 Issue 10 Pages 4045-4054
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Six solvates of griseofulvin with alkyl halide and, alkyl dihalides were isolated, and their crystallographic as well as physico-chemical properties were investigated by infrared spectroscopy, powder X-ray diffractometry, X-ray crystallographic analysis, thermogravimetry (TG) and differential scanning calorimetry (DSC). From the weight loss in TG curves, the combining ratios between the drug and the solvent were determined to be 1: 1 except for that of griseofulvin 1-bromo-2-chloroethane solvate (drug: solvent =1: 0.8). The cell dimensions of griseofulvin bromoethane solvate and griseofulvin dibromomethane solvate were almost equal, and the solvates formed a new type of mixed crystal (substitutional solid solution).
    From X-ray crystallographic analysis, it was elucidated that the molecular arrangement in the dichloroethane solvate crystal was the same as that in the chloroform solvate determined by Shefteret al.
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  • KIYOSHI SHIMIZU, MOTOHARU IWATSURU
    1988 Volume 36 Issue 10 Pages 4055-4059
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    The absorption maximum of a drug in surfactant solution often shifts at surfactant concentrations above the critical micelle concentration (cmc). The first derivative absorption spectrum (FDAS) was used to evaluate the wavelength shift and to measure the cmc of surfactants.
    The cmc's of heptaethylene glycol dodecyl ether (HED), octaethylene glycol dodecyl ether (OED) and sodium dodecyl sulfate (SDS) obtained by the FDAS method were 1.2×10-4, 1.4×10-4 and 7.6×10-3 M, respectively. These cmc values were higher than those obtained by the surface tension method (the Wilhelmy plate method) because of the difference of the positions where the values were estimated on the curve (see text). In the measurement of cmc by the FDAS method, less sample and a shorter time are needed, and the reproducibility of this method is satisfactorily high. Though the FDAS method can be utilized for ionic and nonionic surfactants, it is particularly effective for nonionic surfactants, while the previous methods for cmc measurement of nonionic surfactant are generally cumbersome and time-consuming.
    It was found that the degree of shift-length increased with increasing alkyl chain length of alkylparabens (or alkyl gallates). Therefore, it seems that the use of alkylparabens (or alkyl gallates) of greater alkyl chain length is most convenient in the determination of cmc values by the FDAS method.
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  • YUJI TOKUNAGA, TOMOAKI IWASA, JIRO FUJISAKI, SEIJI SAWAI, AKIRA KAGAYA ...
    1988 Volume 36 Issue 10 Pages 4060-4067
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    A lipophilic prodrug of 1-β-D-arabinofuranosylcytosine (Ara-C), N4-[N-(cholesteryloxycarbonyl) glycyl]-Ara-C (COCG-Ara-C) was entrapped in unilamellar liposomes or solubilized in pH 7.4 phosphate-buffered saline with hydrogenated castor oil polyethylene glycol ether (HCO-60), and its biological disposition was studied in mice. Regardless of dosage form, COCG-Ara-C was accumulated in the liver after intravenous (i.v.) injection, but not in the lung or kidney. In contrast, the blood clearance and spleen distribution of COCG-Ara-C varied with dosage form: slow blood clearance and increased spleen levels of the prodrug were observed for the liposome-entrapped form relative to the detergent-solubilized form. Both COCG-Ara-C preparations successfully maintained the plasma levels of Ara-C compared with Ara-C aqueous solution. However, the plasma Ara-C concentration time profiles were markedly different between the preparations. After i.v. injection of liposome-entrapped COCG-Ara-C, plasma Ara-C levels increased slowly for the first 16h and subsequently decreased gradually. On the other hand, rapid appearance of Ara-C in the circulation and subsequently gradual elimination were observed after injection of the detergent-solubilized prodrug. The relative bioavailabilities obtained with respect to Ara-C aqueous solution were 592% and 129% for the liposome-entrapped and detergent-solubilized forms, respectively. The extremely high bioavailability of liposome-entrapped COCG-Ara-C could be explained in part by the finding that the liposome-entrapped prodrug reduced the plasma clearance of the parent drug Ara-C. These results indicate the potential utility of COCG-Ara-C-bearing liposomes as a sustained-release delivery system of Ara-C applied by i.v. injection.
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  • YUKIHISA KURONO, AKIHIRO FURUKAWA, TAKESHI TSUJI, KEN IKEDA
    1988 Volume 36 Issue 10 Pages 4068-4074
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    The reaction of p-nitrophenyl glycinate (NPG, pKa=7.1) with human serum albumin (HSA) was investigated kinetically at various pH's and 25°C. The Michaelis constant (Ks/m in Nt, where m is the number of reactive sites) and the catalytic rate constant (k2 in s-1) were determined. The affinity of the cationic substrate (NPGH+) to the reactive site is lower than that of the neutral substrate (NPG). The pH profile of k2 is sigmoidal, like that of ko, indicating ionization of the reaction species at pH 6-7. The effect of chemical modification of histidine residues by diethylpyrocarbonate on the reaction rate with NPG and the deuterium oxide isotope effect on the reaction rate of HSA with NPG indicate the reaction of NPG HSA complex with OH- rather than the nucleophilic reaction (formation of glycinated HSA) of the histidine imidazole group (s) with NPG. Results on the reaction in the presence of excess NPG over HSA suggest that HSA has nonspecific multiple reactive sites towards NPG. The reactive sites were considered to be relatively exposed on the surface of the HSA molecule and to be sensitive to conformational change.
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  • ATSUYA YOSHIDA, MASANOBU YAMAMOTO, FUMITOSHI HIRAYAMA, KANETO UEKAMA
    1988 Volume 36 Issue 10 Pages 4075-4080
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Inclusion complexation of digitoxin with β-cycIodextrin (β-CyD) derivatives, such as 2, 6-di-Omethyl-β-CyD (DM-β-CyD), 2, 3, 6-tri-O-methyl-β-CyD (TM-β-CyD), hydroxypropyl-β-CyD (HPβ-CyD, substitution degree 4.3) and hydroxyethyl-β-CyD (HE-β-CyD, substitution degree 4.0) was studied by the solubility method. The apparent 1: 1 stability constant (Kc) of the complexes in water at 25 -C was in the order of DM-β-CyD (84000 m-1)> HP-β-CyD (18000 m-1) =HE-β-CyD (17000 m-1) =β-CyD (17000 M-1)> TM-β-CyD (5600 M -1). From the high-performance liquid chromatographic tracing of each of the four components (digitoxin, bisdigitoxoside, monodigitoxoside, digitoxigenin) in the reaction mixtures, the individual hydrolysis rate constants (K1-K6) were determined by the non-linear least-squares method.β-CyDs suppressed the hydrolysis rates of digitoxin species in an acidic medium (pH 1.2), particularly the appearance of digitoxigenin, the final hydrolysis product, and the inhibitory effect was generally in the order of DM-β-CyD >β-CyD=HP-β-CyD=HE-β-CyD> TM-β-CyD. By analyzing the concentration dependency of the hydrolysis rate, DM-β-CyD was found to decelerate the appearance rate of digitoxigenin more than 2400 times.
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  • KAZUHO ABE, CHAO-HSIUNG WANG, HIKARU TANAKA, HIROSHI SAITO, NORIO MATS ...
    1988 Volume 36 Issue 10 Pages 4081-4087
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    Characteristics of cardiac β-adrenergic responses in Suncus murinus (suncus) were examined in comparison with those of the rat. In both species, isoproterenol produced positive inotropic and chronotropic responses in spontaneously beating right atria and positive inotropic response in electrically driven papillary muscles. However, the effects of β-adrenoceptor stimulation in suncus papillary muscles were considerably smaller than in the rat. Tyramine, an indirect sympathomimetic amine, did not affect the contraction of ventricular muscle in suncus. The affinity and density of specific [3H] dihydroalprenolol binding sites in suncus atrium were close to those in rat atrium. On the other hand, specific [3H] dihydroalprenolol binding sites in suncus ventricle were distinctly lower both in affinity and in density than those of rat ventricle. These results suggest that ventricular β-adrenergic responses in the suncus are markedly smaller than those in the rat, probably due to lower density and affinity of β-adrenoceptors.
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  • NORIAKI IMANISHI, EIJI OHMORI, KIMIO YATSUNAMI, ATSUSHI ICHIKAWA
    1988 Volume 36 Issue 10 Pages 4088-4094
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Hydrocortisone-stimulated synthesis of histidine decarboxylase (EC 4.1.1.22) was studied in rat stomach. Single or daily administration of hydrocortisone increased the histidine decarboxylase activity but not the histamine content in the fundic glands of stomachs from fed and fasted rats with or without adrenalectomy, and also in those from adrenalectomized fasted rats with concomitant treatment with pirenzepine, an inhibitor of gastrin secretion. The increase in histidine decarboxylase activity was maximal at 2 h after the administration of hydrocortisone, and the activity had returned almost to the pretreatment level by 4h after the administration. Furthermore, the increase was not augmented by daily administration of hydrocortisone for 3 d. Cycloheximide prevented the increase in gastric histidine decarboxylase due to hydrocortisone. Rat fundic gland tissue was found to possess binding sites for [3H] glucocorticoids in the cytosol. These results suggest that hydrocortisone stimulates the de novo synthesis of histidine decarboxylase in the fundic gland of rat stomach, though the response is not mediated by changes in the gastrin level.
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  • TAKESHI OHYA, SABURO KANNO
    1988 Volume 36 Issue 10 Pages 4095-4102
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
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    The pathway in the formation of cyanogen chloride from the reaction of 1-naphthol (1) and 4-phenylimidazole with chloramine was investigated. The intermediates isolated in the reaction of 1-naphthol (1) with chloramine were N-chloro-1, 2-naphthoquinone 2-imine (2) and o-carboxycinnamonitrile (6), the latter of which, liberating cyanogen chloride, was finally converted tophthalide-3-carboxylic acid (8). The products obtained in the reaction of 4-phenylimidazole (10) with chloramine were benzonitrile (14), benzoylformic acid (22) and benzoic acid (23) besides cyanogen chloride. Cyanogen chloride formed by the reaction of 4-methylimidazole with [15N]- chloramine was C14NCl. From these results the pathway of cyanogen chloride formation was elucidated.
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  • KAZUYA MITANI, SHUNICHIRO SAKURAI, TOSHIHIRO SUZUKI, KOJI MORIKAWA, EI ...
    1988 Volume 36 Issue 10 Pages 4103-4120
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    α-Isopropyl-α-[3-[3-(3-methoxyphenoxy) propylamino] propyl] -α-phenylacetonitrile derivatives containing various substituents on the benzene ring (A ring) at the phenylacetonitrile moiety were prepared, and their Ca2+-antagonistic activity was evaluated. Among these compounds, the N-Me derivatives with m-OMe, p-F, p-Cl, 3, 4-(OMe) 2 and 3, 5-(OMe) 2 substituents on the A ring were found to show higher Ca2+-antagonistic activity than verapamil. The effect of substituents on the A ring was examined quantitatively using physicochemical substituent parameters and regression analysis. The analysis showed that substituents with a π value close to zero are favorable to the activity and that optimum steric conditions exist for m-and p-substituents, corresponding to those of m-OMe and p-F or p-Cl. The analysis for the whole series of analogs where substituents on the A ring, the benzene ring (B ring) at the phenoxy moiety and the quaternary carbon atom are simultaneously varied suggested that there is an optimum molecular hydrophobicity, perhaps participating in the transport process to the site of action, besides position-specific steric and hydrophobic effects.
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  • KAZUYA MITANI, SHUNICHIRO SAKURAI, TOSHIHIRO SUZUKI, KOJI MORIKAWA, EI ...
    1988 Volume 36 Issue 10 Pages 4121-4135
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    α-[(Phenoxyethylamino) propyy]-α-phenylacetonitrile derivatives possessing various substituents on the benzene ring (A ring) at the phenylacetonitrile moiety, on the quaternary carbon atom and on the benzene ring (B ring) at the phenoxy moiety, and exhibiting various degrees of ablocking activity, were prepared. The variations in the activity were analyzed qualitatively as well as quantitatively by using physicochemical substituent parameters and a regression technique. The effect of substituents on the A ring was rationalized in terms of a parabolic function of their hydrophobic parameter. As regards substituents on the quaternary carbon atom, alkyl groups were desirable for high activity. The effects of substituents on the B ring were such that an optimum hydrophobic condition exists and that an alkoxy substituent at the o-position as well as smaller substituents at the m-and p-positions are favorable for high activity. The analysis for the combined series of analogs where substituents on the A and B rings are varied showed the existence of an optimum hydrophobicity for the whole molecule for the transport process of the molecule, besides above-mentioned various position-specific structural effects.
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  • HIDETOSHI FUJIWARA
    1988 Volume 36 Issue 10 Pages 4136-4143
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Stereospecific decomposition reactions of isomeric molecules of a series of 1-substituted quinolizidin-l-ols have been examined by using electron ionization mass spectra (EI-MS). Inspection of the MS indicates that the molecular ion and the other ions ([M-17] +, m/z154 and 168) for cis-isomers are much more abundant than those for trans-isomers. The configurations of epimers can be distinguished on the basis of the relative intensities of the molecular ion, the ions corresponding to [M-1] +, [M-17] + and [M-29] +, and the ions at m/z 154 and 168 in El-MS, and the peaks due to elimination of a hydroxyl radical from the molecular ion in the ion kinetic energy spectra.
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  • YOSHIRO KOBAYASHI, MASAHARU NAKAJIMA, MASAKAZU NAKAZAWA, TAKEO TAGUCHI ...
    1988 Volume 36 Issue 10 Pages 4144-4147
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Replacement of one fluorine atom of the hexafluorocholesterol derivative (4) with a methoxyl group took place during the saponification of the acetyl groups of 4 with methanolic potassium hydroxide to give the pentafluoromethoxy compound (5), which was converted to the corresponding 1α-hydroxyvitamin D3 form (6). The pentafluoromethoxy compound (6) was found to be about three times more potent than 1 a-hydroxyvitamin D3 in displacing radio-labeled 1, 25-dihydroxyvitamin D3 from the chick intestinal receptor, whereas the activity of 6 in response to bone calciummobilization in vitamin D-deficient rats was slightly lower than that of 1 a-hydroxyvitamin D3.
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  • TSUTOMU NAKANISHI, MARI KOBAYASHI, HIROKO MURATA, AKIRA INADA
    1988 Volume 36 Issue 10 Pages 4148-4152
    Published: October 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    A new pregnane glycoside, named toosendanoside (1), has been isolated from leaves of Melia toosendan SIEB. et Zucc.(Meliaceae). The structure of 1 has been assigned as (20R)-5α-pregnane-2α, 3α, 16β, 20-tetrol 2-O-β-D-glucopyranoside, based on lines of chemical and spectral evidence.
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