Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Volume 48, Issue 12
Displaying 1-36 of 36 articles from this issue
  • Yoshimi HIROKAWA, Tamaki HORIKAWA, Shiro KATO
    2000 Volume 48 Issue 12 Pages 1847-1853
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    An efficient synthesis of 5-bromo-2-methoxy-6-methylaminopyridine-3-carboxylic acid (1), a carboxylic acid moiety of a potent dopamine D2 and D3 and serotonin-3 (5-HT3) receptors antagonist, (R)-5-bromo-N-(1-ethyl-4-methylhexahydro-1, 4-diazepin-6-yl)-2-methoxy-6-methylaminopyridine-3-carboxamide, is described. Reaction of methyl 2, 6-difluoropyridine-3-carboxylate (12) with methylamine in EtOH at -25°C gave a mixture of methyl 2-fluoro-6-methylaminopyridine-3-carboxylate (13) and the regioisomer 14 in a ratio of 57 : 43. On the other hand, reaction of 12 and methyl 2, 6-dichloropyridine-3-carboxylate (16) with sodium methoxide in tetrahydrofuran (THF) and CH2Cl2 provided the 2-methoxypyridine-3-carboxylic esters 20 and 23, respectively, as main products. Similar reaction of 16 in N, N-dimethylformamide (DMF) and MeOH proved to be highly regioselective for the 6-position. A much greater regioselectivity for substitution at the 6-position (>97%) was observed when 16 was treated with 4-methylbenzenethiolate anion in DMF (quantitative yield). After methoxylation of methyl 2-chloro-6-(4-methylbenzenethio)pyridine-3-carboxylate (25b) and successive oxidation of the 6-benzenethio moiety, nucleophilic substitution of the sulfoxide derivative 28 with methylamine gave the 6-methylamino derivative 8. Finally, bromination of 8 and alkaline hydrolysis produced the desired product 1 in an overall yield of 67%.
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  • Jun TODA, Michiya SAKAGAMI, Yoko GOAN, Mina SIMAKATA, Toshiaki SAITOH, ...
    2000 Volume 48 Issue 12 Pages 1854-1861
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    The thionium ions 10 generated by Pummerer reaction of N-aryl-N-methyl-3-(phenylsulfinyl)propionamides 4 caused not only an electrophilic cyclization reaction producing 2-quinolones 8, but also the formation of the vinyl sulfides 5 and 6 in favor of the latter reaction. On the other hand, the treatment of the vinyl sulfides 5 and 6 with p-toluenesulfonic acid induced cyclization to afford the 2-quinolones 8 in excellent to moderate yields, depending on the electronic properties of the aromatic ring, thus providing a convenient method for the snthesis of methoxy-2-quinolones.
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  • Yen-Cheng LI, Yueh-Hsiung KUO
    2000 Volume 48 Issue 12 Pages 1862-1865
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    Three new lignans, ficusal (1) and ficusesquilignans A (2), B (3) and one new γ-lactone, ficusolide diacetate (4), were isolated from the wood of Ficus microcarpa L.f. Their structures were determined by spectral evidence.
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  • Abolghasem JOUYBAN-GHARAMALEKI, Brian J. CLARK, Jr. ACREE
    2000 Volume 48 Issue 12 Pages 1866-1871
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    The capability of the extended forms, of two well established cosolvency models, i.e. the combined nearly ideal binary solvent/Redlich-Kister equation and the modified Wilson model, used to predict the solute solubility in non-aqueous ternary solvent mixtures is presented. These predictions are based on the measured solubilities of anthracene in binary solvent mixtures. As a result the values of average percent deviations were less than 2% for the anthracene solubility in ternary mixtures.This work was also extended to other cosolvency models, i.e. the extended Hildebrand solubility approach and the mixture response surface method, which are also commonly used for correlating solubility data in ternary solvents. The accuracy of the models is compared with each other and also with a published solubility model for ternary mixtures. The results illustrate that all models produced comparable accuracy.
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  • Benoit JOSEPH, David ALAGILLE, Jean-Yves MEROUR, Stephane LEONCE
    2000 Volume 48 Issue 12 Pages 1872-1876
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    A new series of N-substituted benzo[5, 6]cyclohepta[b]indole derivatives were synthesised and evaluated for in vitro cytotoxic activities against L1210 murine leukemia and HT29 cell lines. Among them, several compounds showed potent antitumor activity and blocked cell cycle progression of L1210 cells in G2+M phase.
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  • Hajnalka GOCZO, Piroska SZABO-REVESZ, Bela FARKAS, Magdolna HASZNOS-NE ...
    2000 Volume 48 Issue 12 Pages 1877-1881
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    The production of spherical crystals has recently gained great attention due to the fact that the crystal habit (form, surface, size, etc.) can be modified during the crystallization process. Spherical crystals of ASA were developed by non-typical and typical spherical crystallization techniques. The non-typical spherical crystallization process (conventional stirred tank method) resulted in few monocrystals and non-spherical crystal agglomerates. The typical spherical crystallization process was carried out by the three solvent-system (ethanol-water-carbon tetrachloride). The products were qualified by morphological study, NIR investigation, salicylic acid content, dissolution rate, studies on flowability, compactibility, cohesivity and tablettability. The results demonstrate that only typical spherical crystallization can be recommended for the production of spherical crystals of ASA. Only product made by this technique shows excellent flow properties and favourable compactibility, cohesiveness and tablettability values.
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  • Shin-ichi KONDO, Isao HATAKEYAMA, Shouichi HOSAKA, Masayuki KUZUYA
    2000 Volume 48 Issue 12 Pages 1882-1885
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    From the standpoint of the mechanism of mechanochemical polymerization, two kinds of copolymeric prodrug, whose monomer sequence distribution (MSD) is different from each other, can be prepared by this polymerization under appropriate operational conditions : one is a random copolymer abundant in the longer block consisting of the same repeating units (multi-block copolymer), and the other is a block copolymer. To confirm the difference of MSD, the 13C-NMR spectra of poly(acrylamide-co-sodium acrylate) prepared by mechanochemical polymerization were measured and compared with the spectrum of that synthesized by a conventional radical-initiated solution polymerization, which produces the random copolymer normally. The results show that MSD in copolymers depends on the polymerization method (operational condition). We prepared three kinds of copolymeric prodrug consisting of acrylamide and vinyl monomer of 5-fluorouracil, whose MSD is different from one another. These copolymeric prodrugs had almost the same number average molecular weight, particle diameter and composition, and differed only in MSD. We compared the rate of drug release of these copolymeric prodrugs. The rate of drug release was the highest with the random copolymer, followed by the mechanochemically produced multi-block copolymer and the block copolymer. This result suggests that the rate of drug release depends on MSD of copolymeric prodrugs. These results are useful as they give a fundamental insight into the synthesis of copolymeric prodrugs having the desired rate of drug release.
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  • Ange Desire YAPI, Mustofa MUSTOFA, Alexis VALENTIN, Olivier CHAVIGNON, ...
    2000 Volume 48 Issue 12 Pages 1886-1889
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    Several diaza-analogs of phenanthrene derived from 3-amino, 5-amino, 6-amino, 8-aminoquinolines, and 5-aminoisoquinoline were prepared to eveluate their antiplasmodial activities. All compounds showed mild to good activity in vitro, both on a Nigerian chloroquino-sensitive strain and on the chloroquino-resistant FcB1-Columbia and FcM29 strains. The position of the intracyclic nitrogen atom is shown to be crucial for the activities (best results are obtained with a 1, 10-phenanthroline skeleton). In regard to the particular properties of this structure (metalloprotease inhibition activity by chelating divalent metal ions), the potential chelating site of the molecule was blocked. In this case, the biological activity of the compound was greatly enhanced, showing that the mechanism of action of such a compound is probably not correlated to metalloprotease inhibition activity.
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  • Shun-Li WANG, Shan-Yang LIN, Ting-Fang CHEN
    2000 Volume 48 Issue 12 Pages 1890-1893
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    The pathway of dehydration and intramolecular cyclization of lisinopril dihydrate in the solid state was investigated using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and a combination of thermal analyzer with Fourier transform infrared microspectroscopy (thermal FT-IR microscopic system). The results indicate that the dehydration from the solid-state lisinopril dihydrate had a two-step process from dihydrate to monohydrate at 76°C and then from monohydrate to anhydrate at 99-101°C, which could be clearly observed from the above three methods. Only the thermal FT-IR microscopic system could give vital information on diketopiperazine (DKP) formation via intramolecular cyclization in anhydrous lisinopril. A new peak at 1670 cm-1 assigned to the carbonyl band of DKP formation was clearly evidenced. The water of reaction by-product was liberated at a temperature >157°C and appeared on the IR spectra near 3200-3400 cm-1. Moreover, the peak at 1574 cm-1 assigned to carboxylate shifted to 1552 cm-1 due to the DKP formation. The peak at 1670 cm-1 related to the DKP formation changed slightly in intensity from 147°C and significantly near 157°C. DSC and TGA methods were poor for use in supplying information on DKP formation in lisinopril. The thermal FT-IR microscopic system is useful from the view point that it can quickly and directly show the solid-state stability of drug.
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  • Koji URAKAMI, Yuka SAITO, Yasuhiro FUJIWARA, Chuichi WATANABE, Kazuich ...
    2000 Volume 48 Issue 12 Pages 1894-1897
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    Thermal desorption (TD) techniques followed by capillary GC/MS were applied for the analysis of residual solvents in bulk pharmaceuticals. Solvents desorbed from samples by heating were cryofocused at the head of a capillary column prior to GC/MS analysis. This method requires a very small amount of sample and no sample pretreatment. Desorption temperature was set at the point about 20°C higher than the melting point of each sample individually. The relative standard deviations of this method tested by performing six consecutive analyses of 8 different samples were 1.1 to 3.1%, and analytical results of residual solvents were in agreement with those obtained by direct injection of N, N-dimethylformamide solution of the samples into the GC. This novel TD/GC/MS method was demonstrated to be very useful for the identification and quantification of residual solvents in bulk pharmaceuticals.
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  • Takeshi KOIKE, Yoshifumi SHINOHARA, Seisho TOBINAGA, Naoki TAKEUCHI
    2000 Volume 48 Issue 12 Pages 1898-1902
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    The Pictet-Spengler reaction of tryptamine type 1, 2-dihydropyridine 5c derived from the cycloaddition of the sec-nitrodienamine 3c with acetaldehyde afforded the indoloquinolizine derivatives 6 and 7.
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  • Kazuhiko TAKE, Kazuo OKUMURA, Kazunori TSUBAKI, Kiyoshi TANIGUCHI, You ...
    2000 Volume 48 Issue 12 Pages 1903-1907
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    FK584[(-)-N-tert-butyl-4, 4-diphenyl-2-cyclopentenylamine hydrochloride, (-)-4·HCl], a potential candidate for the treatment of overactive detrusor, was synthesized in a 4-step approach starting with Sharpless oxidation of cyclopentenol 6 (kinetic resolution). This epoxidation is a rare case in that the empirical rule does not work. Regio- and stereoselective introductin of tert-butylamine to the obtained epoxycyclopentanol 5 and subsequent conversion of the resulting diol to an olefin completed the synthesis. The absolute configuration of FK584 was determined to be S by X-ray crystallographic analysis of the salt of S-(+)-mandelic acid.
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  • Fumiko ABE, Tatsuo YAMAUCHI
    2000 Volume 48 Issue 12 Pages 1908-1911
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    Five new megastigmane glucosides and one of their aglycones were isolated, along with (6S, 9R)-roseoside, from the polar fraction of the leaves of Asclepias fruticosa, and the structures were determined by spectroscopic methods. Most of them have an epoxy-linkage between C-5 and C-11. The configurations at C-3 and C-9 for each compound were confirmed to be S and R, respectively, by application of the modified Mosher's method.
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  • Feng-Peng WANG, Jin-Song YANG, Qiao-Hong CHEN, Lin YU, Bo-Gang LI
    2000 Volume 48 Issue 12 Pages 1912-1916
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    New access to the 7, 17-seco norditerpenoid alkaloids 9 (60%) from yunnaconitine (5), as well as 14 (46%) and 15 (22%) from isotalatizidine (10), via selective hydrolysis, chlorination and reduction with NaBH4 is described.
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  • Masanori KUROYANAGI, Kazumasa SUGIYAMA, Masahiro KANAZAWA, Nobuo KAWAH ...
    2000 Volume 48 Issue 12 Pages 1917-1920
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    From the needles of Abies sachalinensis, novel rearranged lanostane type triterpenes, 1-4, were isolated along with a known triterpene (5). The structures of the new compounds, 1-4, were elucidated to be 3, 4-seco-8-(14→13R)abeo-17, 13-friedo-9β-lanosta-4(28), 7, 14(30), 22Z, 24-pentaen-26, 23-olide-3-oic acid, methyl 3, 4-seco-8-(14→13R)abeo-17, 13-friedo-9β-lanosta-4(28), 7, 14(30), 22Z, 24-penten-26, 23-olide-3-oate, 3, 4-seco-8(14→13R)abeo-17, 13-friedo-9β-lanosta-4(28), 7, 14, 22Z, 24-pentaene-26, 23-olide-3-oic acid and methyl 3, 4-seco-8(14→13R)abeo-17, 13-friedo-9β-lanosta-4(28), 7, 14, 22Z, 24-pentaene-26, 23-olide-3-oate, respectively, by means of spectral experiments, especially two dimensional NMR spectroscopy, such as 1H-detected multiple quantum coherence (HMQC), 1H-detected heteronuclear multiple bond connectivity (HMBC) and 1H-1H-correlation spectroscopy (COSY) experiments. These new compounds have novel structures containing A-seco, rearranged spiro structure and a γ-lactone conjugated with a diene. Some of these compounds showed potent antibacterial activity against gram positive bacteria.
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  • Sun Dong YOO, Hun JUN, Beom Soo SHIN, Hye Suk LEE, Myung Ok PARK, Patr ...
    2000 Volume 48 Issue 12 Pages 1921-1924
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    This study first reports the pharmacokinetic disposition of polyethylene glycol (PEG)-modified salmon calcitonin (sCT) based on the number of attached PEG molecules. PEG-modified sCT was prepared by covalent linkage with succinimidyl carbonate monomethoxy polyethylene glycol. Mono- and di-PEG-sCTs were separated by size exclusion and reverse phase HPLC, and radioiodinated by the chloramine-T method with Na125I. 125I-mono-PEG sCT, 125I-di-PEG-sCT and unmodified 125I-sCT were administered to rats by i.v. injection. Serial blood samples, urine and various tissue samples were taken for the determination of radioactivity. Di-PEG-sCT exhibited significantly reduced systemic clearance (2.3 vs. 11.1 ml/min/kg) and steady-state volume of distribution (229.9vs. 603.1 ml/kg), while mono-PEG-sCT showed a prolonged elimination half-life (189.1 min vs. 59.8 min) compared with unmodified sCT. The extent of urinary excretion of the PEG-modified sCTs was higher than for the unmodified sCT, but all these chemicals were excreted in urine in small quantities (≤0.6%). There was a tendency toward reduced accumulation of PEGylated sCTs in tissues, with its reduction being inversely proportional to the molecular size. Accumulation of the total radioactivity of the unmodified and PEG-modified sCTs was highest in the liver, followed by kidneys, lungs, spleen, heart and thyroid. When expressed per tissue gram weight, however, the highest radioactivity was found in the kidneys. PEGylated sCTs may have greater therapeutic potential via reduced systemic clearance and prolonged elimination half-life over unmodified sCT.
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  • Yukihiro TAKEBAYASHI, Hironobu KOGA, Junji TOGAMI, Akio INUI, Hiroyuki ...
    2000 Volume 48 Issue 12 Pages 1925-1929
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    We previously reported that a cyclic octapeptide amide, c[D-Cys29, Cys34]NPY Ac-29-36 (YM-42454) showed a high affinity for Y1-receptors in SK-N-MC cells (Ki=0.047μM) but not for Y2-receptors in the porcine hippocampus membranes (Ki>10μM). To explore the critical residues of this unique cyclic peptide for Y1-binding activity, the structure-affinity relationships were investigated by means of amino acid replacement. The results indicated that the hydrophobic side-chains of Leu30 and Ile31, the guanidinium groups of Arg33 and Arg35, and the C-terminal amide are critical for the binding affinity of YM-42454 to the Y1-receptor. On the other hand, Thr32 in YM-42454 might not be critical for the Y1-binding affinity. 1H-NMR studies for YM-42454 and its derivatives have suggested that the critical residues are involved in the direct interaction with a Y1-receptor rather than in maintaining the bioactive conformation.
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  • Yuka INATOMI, Akira INADA, Hiroko MURATA, Masatoshi NISHI, Tsutomu NAK ...
    2000 Volume 48 Issue 12 Pages 1930-1934
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    From a whole plant of a fern, Diplazium subsinuatum, three new hopane-triterpene lactone glycosides, diplaziosides V-VII (1-3), were isolated, together with a new monoacetyl derivative (4) of diplazioside VII (3). Compounds 1-3 were defined as the respective 3-O-[β-D-glucopyranosyl-(1→2)]-β-D-glucopyranosides of 3β, 24-dihydroxyhopan-28, 22-olide (1), of 3β, 17, 24-trihydroxyhopan-28, 22-olide (2), and of (22R)-3β, 24, 30-trihydroxyhopan-28, 22-olide (3), and 4 as the 6"-O-acetate of 3, respectively, on the basis of spectral evidence. 1-3 are new in their glycoside structures but also in their triterpene structures. Furthermore, in compounds 1-4, the coupling between the 24-hydroxy proton and one of the 24-methylene protons showed a very large J-value (11.4Hz); based on this 1H-NMR evidence, etc., preferred conformations of the 24-hydroxymethylene groups in 1-4 are also inferred. In a similar manner, 1H-NMR coupling patterns of the 24-hydroxymethylene in the monoglucoside (2a) and aglycone (2b), derived from 2, are also reported and discussed here.
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  • Tomoyuki KITAZAKI, Takashi ICHIKAWA, Akihiro TASAKA, Hiroshi HOSONO, Y ...
    2000 Volume 48 Issue 12 Pages 1935-1946
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    New optically active antifungal azoles, N-[4-(azolyl)phenyl]- and N-[4-(azolylmethyl)phenyl]-N'-[(1R, 2R)-2-(2, 4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1, 2, 4-triazol-1-yl)propyl]azolones (1, 2, 3), were prepared in a stereocontrolled manner. Compounds 1-3 showed strong antifungal activity against Candida albicans in vitro. Among them, the imidazolidinones 3 showed a broad antifungal spectrum in vitro as well as potent in vivo activity against candidiasis and aspergillosis in mice. The imidazolidinones (3i, j, k) having 1H-1, 2, 3-triazol-1-yl, 2H-2-tetrazolyl and 1H-1-tetrazolyl moieties were found to exert strong protective effect against aspergillosis.
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  • Takashi ICHIKAWA, Tomoyuki KITAZAKI, Yoshihiro MATSUSHITA, Hiroshi HOS ...
    2000 Volume 48 Issue 12 Pages 1947-1953
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    New routes for the synthesis of the optically active antifungal triazoles 1-[(1R, 2R)-2-(2, 4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1, 2, 4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1b) and the 3-[4-(1H-1, 2, 3-triazol-1-yl)phenyl]-2-imidazolidinone analog (1a) that possess an imidazolidine nucleus were established. The key synthetic intermediates, (2R, 3R)-3-(2, 2-diethoxyethyl)amino-2-(2, 4-difluorophenyl)-1-(1H-1, 2, 4-triazol-1-yl)-2-butanol (8) and (2R, 3R)-2-(2, 4-difluorophenyl)-3-(2-hydroxyethyl)amino-1-(1H-1, 2, 4-triazol-1-yl)-2-butanol (14), were prepared by the ring-opening reaction of the oxirane (2) with the corresponding 2-substituted ethylamines. The acetal (8) was converted to the imidazolidinones (1a, b) by condensation with the carbamates (10a, b) followed by treatment with hydrochloric acid and subsequent catalytic hydrogenation. The candidate selected for the clinical trials, 1b (TAK-456), was alternatively prepared from the hydroxyethylamino intermediate (14) via two reaction steps : condensation with the carbamate (10b) to the urea (15) and subsequent cyclization to the imidazolidinones. This newly developed synthetic route could be applied to a large scale preparation of 1b.
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  • Norio SHIBATA, Zhaopeng LIU, Yoshio TAKEUCHI
    2000 Volume 48 Issue 12 Pages 1954-1958
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    Enantioselective fluorinating agents, (R)- and (S)-N-fluoro-3-tert-butyl-7-nitro-3, 4-dihydro-2H-benzo[e][1, 2]-thiazine 1, 1-dioxides (BNBT-F, 2) are readily prepared in 3 steps from racemic 3-tert-butyl-7-nitro-3, 4-dihydro-2H-benzo[e][1, 2]thiazine 1, 1-dioxides (5) via optical resolution and fluorination. These agents make accessible both enantiomers of optically active quaternary α-fluoro carbonyl compounds in modest to high enantioselectivities. X-ray crystallographic analysis of chiral 2 reveals a unique structure wherein the nitrogen atom is highly pyramidalized and fluorine occupies an axial position.
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  • Tetsuro ITO, Toshiyuki TANAKA, Yoshimi IDO, Ken-ichi NAKAYA, Munekazu ...
    2000 Volume 48 Issue 12 Pages 1959-1963
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    Four new C-glucopyranosides of resveratrol oligomers, hemsleyanosides A-D, were isolated from the bark of Shorea hemsleyana. The structures were established on the basis of spectroscopic evidence, influding 1H-1H and 1H-13C long-range couplings and nuclear Overhauser effect experiments in the NMR spectrum.
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  • Yoshio OKADA, Yuko TSUDA, Mayako TADA, Keiko WANAKA, Utako OKAMOTO, Ak ...
    2000 Volume 48 Issue 12 Pages 1964-1972
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    Based on structure-activity relationship studies, we designed and synthesized plasmin (PL) and plasma Kallikrein (PK) inhibitors. Trans-(4-aminomethylcyclohexanecarbonyl)-Tyr(O-Pic)-octylamide inhibited PL, PK, urokinase (UK) and thrombin (TH) with IC50 values of 0.53, 30 5.3 and >400μM, respectively. Trans-(4-aminomethylcyclohexanecarbonyl)-Tyr(O-2-Pyrim)-4-carboxyanilide inhibited PL, PK, UK and TH with IC50 values of 36, 0.56, 440 and >1000μM, respectively.
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  • Chisako YAMAGAMI, Miyako HARAGUCHI
    2000 Volume 48 Issue 12 Pages 1973-1977
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    We recently proposed a new H-accepting scale, SHA, for monosubstituted pyrazines, and demonstrated that this parameter works effectively in expressing the relationship between log P (P : 1-octanol/water partition coefficient) and log k' (k' : retention factor derived from reversed phase liquid chromatography) with aqueous methanol solutions as the mobile phase, according to the equation : log k'=α log P+ρσI+sSHA+const., where σI represents the electronic substituent constant. In this work, we have extended the same treatment to analysis of log k' measured in mobile phases containing different organic modifiers such as 1-propanol, acetonitrile, and dioxane, and found that the above equation is still useful. By comparing the correlations obtained, it was confirmed that parameter SHA could be universally utilized for representing the difference in H-bonding effects involved in different partitioning systems.
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  • Teruo KOMOTO, Hiroyuki HIROTA, Mari OTSUKA, Jiro KOTAKE, Susumu HASEGA ...
    2000 Volume 48 Issue 12 Pages 1978-1985
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    New fibrates containing piperidine, 4-hydroxypiperidine, piperidin-3-ene, and piperazine moieties in the structures were synthesized and evaluated. Among the synthesized compounds, 2-[3-[1-(4-fluorobenzoyl)-piperidin-4yl]phenoxy]-2-methylpropanoic acid (9aA : AHL-157) showed very superior activities in decreasing triglyceride, cholesterol, and blood sugar compared to bezafibrate in mice and rats.
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  • Hiroki AKASAKA, Tomohiro ENDO, Hiromasa NAGASE, Haruhisa UEDA, Shoichi ...
    2000 Volume 48 Issue 12 Pages 1986-1989
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    The complex forming ability of δ-cyclodextrin δ-CD with 7 kinds of macrocyclic compounds (MCCs) with 8-15 carbon atoms in the ring as models of large guest molecules was studied in aqueous solution and compared with the complexation properties of α-, β- and γ-CD. Both α- and β-CD formed relatively stable complexes with small MCCs, while γ- and δ-CD were more efficient in binding larger MCCs. The solid MCC/δ-CD complexes were precipitated with the larger MCCs with 11-15 carbon atoms in the ring, while no such precipitates were obtained with smaller MCCs with only 8-10 carbon atoms in the ring. The formation of the solid complexes was confirmed by powder X-ray diffractometry and differential scanning calorimetry. The cell dimensions of cycloundecanone (11 carbon atoms in the ring)/δ-CD complex were determined by X-ray crystallography. The preliminary crystal data were : Monoclinic, P21, a=32.50 (2) Å, b=19.02 (3) Å, c=16.60 (1) Å, β=98.37 (5)°, V=10148 (16) Å3.
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  • Young Sook YUN, Naoki SUGIMOTO, Setsuko SEKITA, Tamio MAITANI, Takashi ...
    2000 Volume 48 Issue 12 Pages 1990-1991
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    Chemical constituents of MeOH extracts of cigarette smoke were studied. Two new alkaloids, named cigatin A (1), 2-(Pyridine-3-yloxy)-benzene-1', 4'-diol and B (2), 2(4-Methyl-pyridin-3-yloxy)-benzene-1', 4'-diol, were isolated from a mainstream condensate of cigarette together with seven known alkaloids. Their structures were determined on the basis of spectral data and chemical methods.
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  • Shyh-Yuan LI, Ming-Der WU, Chi-We WANG, Yao-Haur KUO, Ray-Ling HUANG, ...
    2000 Volume 48 Issue 12 Pages 1992-1993
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    A novel C19 homolignan, taiwanschirin D (1), possessing a 3, 4-{1-[(Z)-2-methoxy-2-oxoethylidene]}pentano (2, 3-dihydrobenzo[b]furan)-3(2-oxoacetate) skeleton, was isolated from the stem of Kadsura matsudai HAYATA. Its structure was determined from physical and spectral data including 2D NMR spectra. The Anti-HBeAg test revealed that taiwanschirin D (1) had moderate activity at a concentration of 94.3μM (50μg/ml).
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  • Erdal BEDIR, Ihsan CALIS, Sonia PIACENTE, Cosimo PIZZA, Ikhlas A. KHAN
    2000 Volume 48 Issue 12 Pages 1994-1995
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    A new flavonol glycoside, isorhamnetin 3-O-β-D-apiofuranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→6)]-β-D-galactopyranoside, and the known diglycoside, isorhamnetin 3-O-α-L-rhamnopyranosyl-(1→6)-β-D-galactopyranoside were isolated from the aerial parts of Astragalus vulneraria. Characterization of the two compounds was done by spectroscopic methods (1D and 2D NMR, and FAB-MS).
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  • Ehab A. ABOURASHED, Ikhlas A. KHAN
    2000 Volume 48 Issue 12 Pages 1996-1998
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
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    The styryl α-pyrones, d-kawain (1) and d-methysticin (2) are two of the major kavalactone constituents of the anxiolytic herb Piper methysticum, commonly known as kava. The use of fungal models to mimic the mammalian metabolism of 1 resulted in the production of 4'-hydroxykawain (1a) from the culture broth of Cunning-hamella elegans (ATCC 9245), the same metabolite identified in rat urine. The fungus Torulopsis petrophilum (ATCC 20225) biotransformed 2 to 3'-hydroxy-4'-methoxykawain (2c) which is analogous, but not identical, to a known rat metabolite of methysticin.
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  • Tomihiro NISHIYAMA, Yasuhiro ONO, Sachiko KUROKAWA, Saori KIMURA
    2000 Volume 48 Issue 12 Pages 1999-2002
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    The direct α-bromination of various ketones using trifluoromethanesulfonic anhydride and Grignard reagent or magnesium bromide in ether gave the corresponding α-bromo ketones in moderate to good yields under mild reaction conditions.
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  • Masaji SUZUKI, Yutaka OHUCHI, Hajime ASANUMA, Toshie KANEKO, Sadakazu ...
    2000 Volume 48 Issue 12 Pages 2003-2008
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    A series of N-azabicycloalkyl-1-alkyl-2-oxo-1, 2-dihydro-3-quinolinecarboxamides were synthesized and tested for serotonin 5-HT4 receptor-stimulating effects in the regulation of electrically-evoked contraction in guinea pig muscle. Among them, N-azabicycloalkyl-1-isopropyl-2-oxo-1, 2-dihydro-3-quinolinecarboxamide (8c, 9c, 10c, 11c, 12c) exhibited potent serotonin 5-HT4 receptor-stimulating activity. The most potent compound, N-(endo-8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1, 2-dihydro-3-quinolinecarboxamide (8c, ED50=36.3 nM), was seven times as active as cisapride, while 8c had no affinity for 5-HT1A, 5-HT1D, D2, muscarinic M2 or muscarinic M3 receptors even at 10μM. Compound 8c stimulated digestive tract motility in conscious fed dogs (1.0 mg/kg p.o.).
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  • Nikolas FOKIALAKIS, Prokopios MAGIATIS, Sofia MITAKU, Francois TILLEQU ...
    2000 Volume 48 Issue 12 Pages 2009-2010
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    Two new alkaloids, megistonine I (1) and megistonine II (2), were isolated from the bark of Sarcomelicope megistophylla. Their structures, which are derived from the 3-methoxy-4-quinolone basic skeleton, were elucidated on the basis of MS and extensive NMR studies.
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  • Kenichiro TODOROKI, Yoshihito OHBA, Kiyoshi ZAITSU
    2000 Volume 48 Issue 12 Pages 2011-2013
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    We synthesized N-(4-substituted benzyl)isoluminol which has 4-bromo-, 4-methyl-, 4-methoxy-, 4-nitro-groups. These compounds produced chemiluminescence by the reaction with the oxidizing agent, potassium hexacyanoferrate and hydrogen peroxide, in an alkaline medium. The chemiluminescence intensites of these compounds were 0.03-4.7 times that of isoluminol. We used Hamett substituent constants as a parameter for the electronic substituent effects. The relationship between the amino-H chemical shift value and the Hamett substituent constants showed a good linear correlation. The relationship between the chemiluminescence intensities and the Hamett substituent constants showed a good linear correlation. The relationship between the fluorescence intensities and the Hamett substituent constants also showed a good linear correlation. The results suggest that the change in the electron density around the amino group strongly influences the fluorescence intensities and corresponding chemiluminescence intensities of these derivatives.
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  • Kiyosei TAKASU, Hisashi MIYAMOTO, Kiyoshi TANAKA, Tohru TAGA, Masahiko ...
    2000 Volume 48 Issue 12 Pages 2014-2016
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    Monohydrochlorides of cis-2, 5-diphenylpiperazine assume a chair conformation, while the corresponding dihydrochlorides assume a boat form regardless of the substituent(s) at the nitrogen atom.
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  • Yumiko YAMANO, Yasuko WATANABE, Naoharu WATANABE, Masayoshi ITO
    2000 Volume 48 Issue 12 Pages 2017-2018
    Published: December 01, 2000
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    A stereocontrolled synthesis of optically active β-D-glucopyranosides 1-4 of 3-hydroxy-7, 8-didehydro-β-ionol utilizing an asymmetric transfer hydrogenation to α, β-acetylenic ketones catalyzed by chiral ruthenium complexes as the key step is described.
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