Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
53 巻, 4 号
選択された号の論文の24件中1~24を表示しています
Regular Articles
  • Satoru Watano, Takumi Okamoto, Yoshinobu Sato, Yoshifumi Osako
    2005 年 53 巻 4 号 p. 351-354
    発行日: 2005年
    公開日: 2005/04/01
    ジャーナル フリー
    Scale-up of wet granulation in a vertical high shear mixer was conducted. Pharmaceutical excipient powders composed of lactose, cornstarch and micro-crystallinecellulose, and hydroxypropylcellulose as a binder were mixed together and then granulated with purified water under various operating conditions and vessel scales. A novel internal stress measurement system was developed and stress of normal and tangential directions that granules received from the agitator blade during the granulation was continuously measured. The results indicated that granules received stress mainly from the tangential direction, which also showed the largest value near at the vessel wall. The effects of the agitator tip speed and the centrifugal acceleration on the measured stress was investigated. It was found that the tip speed of the agitator blade could be the main factor for the granule growth. The physical properties such as strength, size distribution and compressibility of granules prepared by changing the operating conditions and the vessel scales were evaluated and the scale-up characteristics of high shear granulation were investigated experimentally. The results showed that these physical properties had linear correlations with the tip speed. It was finally concluded that the scale-up of high shear granulation could be well conducted by means of the tip speed of the agitator blade.
  • Okiko Miyata, Hiroshi Asai, Takeaki Naito
    2005 年 53 巻 4 号 p. 355-360
    発行日: 2005年
    公開日: 2005/04/01
    ジャーナル フリー
    The imino 1,2-Wittig rearrangement of hydroximates containing a furan ring provides a novel method for the synthesis of β-hydroxy-α-amino acids. Upon treatment with LDA, hydroximates smoothly underwent the rearrangement to give Z-2-hydroxyoxime ethers in good yield, which were converted into both cis- and trans-oxazolidinones with high stereoselectivity. The cis- and trans-oxazolidinones were stereoselectively converted into erythro- and threo-β-hydroxyphenylalanines, respectively, via the oxidative cleavage of a furan ring, ring-opening of oxazolidinone, and deprotection.
  • Hideki Kanho, Sayaka Yaoya, Nobuo Kawahara, Takahisa Nakane, Yoichi Ta ...
    2005 年 53 巻 4 号 p. 361-365
    発行日: 2005年
    公開日: 2005/04/01
    ジャーナル フリー
    The glucosylation of some coumarin and flavone derivatives on incubation with the hairy roots of morning glory (Pharbitis nil) was previously reported. We further studied the biotransformation of benzaldehyde- and acetophenone-type derivatives. Vanillin and isovanillin were reduced to alcoholic derivatives and glucosylated at the phenolic and the alcoholic hydroxyl groups. In the case of 3,4-dihydroxybenzaldehyde, the formyl group was reduced and the 3-hydroxyl or 4-hydroxyl groups were glucosylated to give monoglucosides. The 3-hydroxyl group was predominantly glucosylated to the 4-hydroxyl group. 4-β-D-Glucopyranosyloxy-3-methoxybenzylalcohol was obtained in low yield. In time-course experiments with vanillin, it was found that the high-level reduction of the formyl group and glucosylation of the phenolic hydroxyl group occurred, and finally 4-O-β-D-glucopyranosylvanillylalcohol was obtained as the main product. In the case of 3,4-dimethoxybenzaldehyde, 3,4,5-trimethoxybenzaldehyde, and salicylaldehyde, the formyl groups were reduced, and then the hydroxyl groups at the benyl position were glucosylated to give alcoholic glucosides in relatively high yields. In 4-hydroxy-3-methoxyacetophenone, the 4-hydroxyl group was glucosylated and two dimerized glucosides, biphenyl and biphenylether types, were obtained in low yields. In acetophenone, 1-β-D-glucopyranosyloxy-1-phenylethane and 2-β-D-glucopyranosyloxyacetophenone were obtained. As mentioned above P. nil hairy roots showed various biotransformative activities including glucosylation of phenolic and benzylic hydroxyl groups, reduction of the formyl group near the benzene ring, and phenol oxidation dimerization. The glucosylation reaction was especially interesting for the production of valuable glucosides.
  • Yue Wang, Nobuo Okabe
    2005 年 53 巻 4 号 p. 366-373
    発行日: 2005年
    公開日: 2005/04/01
    ジャーナル フリー
    The crystal structures of the series of four ternary complexes, [Pd(phen)(2,6-PDCA)]·4H2O (1) (phen=1,10-phenanthroline; 2,6-PDCA=2,6-pyridinedicarboxylic acid), [Pd(bpy)(2,3-PDCA)]·3H2O (2) (bpy=2,2′-bipyridineand; 2,3-PDCA=2,3-pyridinedicarboxylic acid) and [Pd(phen)(PHT)]·2.5H2O (3) (PHT=o-phthalic acid ) and [Pd(bpy)(PHT)]·1.5H2O (4), are determined and the coordination modes of palladium(II) ternary complexes are characterized. All complexes take the mononuclear Pd(II) complexes, in which central Pd(II) atom of each complex has a similar distorted square-planar four coordination geometry. In all complexes, the aromatic heterocyclic compounds, phen and bpy, behave as a bidentate N, N′ ligand. In the complex 1 and 2, 2,6-PDCA and 2,3-PDCA behave as a bidentate N, O ligand, and in complex 3 and 4, PHT behaves as a bidentate O, O′ ligand.
  • Hideji Tanaka, Xiangli Liu, Daichi Kawabata, Hiroshi Chuman, Chisako Y ...
    2005 年 53 巻 4 号 p. 374-377
    発行日: 2005年
    公開日: 2005/04/01
    ジャーナル フリー
    The chloroform/water distribution coefficients (KD) of sixteen diazine compounds were determined by a stepwise flow ratiometry. An aqueous solution of analyte was delivered and merged with chloroform. The flow rate ratio of both the phases was varied stepwise under a constant total (chloroform+aqueous) flow rate. The analyte was extracted to chloroform while both the phases, which were segmented by each other, were passing through an extraction coil. The segmented stream was then led to a UV/Vis detector directly without phase-separation. The absorbance of the chloroform and aqueous phases (Ao and Aa, respectively) was each measured at the maximum absorption wavelength of the analyte. The plots of A−1 against Rf, (ARf)−1 against Rf−1, and ARf against A gave straight lines, where A was Ao, Aa or the sum of them (AS). The KD of the analyte was calculated from the slopes and intercepts of the plots. The log KD values obtained for the analytes (−0.5—1.4) were agreed well with the values measured by a shake-flask method. The present method is simple, rapid (5 min/determination) and applicable to the volatile compounds with reasonable precision (standard deviation of log KD<0.07).
  • Viqar Uddin Ahmad, Afsar Khan, Umar Farooq, Farzana Kousar, Saleha Sul ...
    2005 年 53 巻 4 号 p. 378-381
    発行日: 2005年
    公開日: 2005/04/01
    ジャーナル フリー
    Three new tricyclic cis-clerodane type diterpenoids trivially named as limbatolide A (1), limbatolide B (2) and limbatolide C (3) have been isolated from the roots of Otostegia limbata along with two known compounds; oleanic acid and β-sitosterol. The structure elucidation of the new compounds was based primarily on two-dimensional (2D) NMR techniques. Compounds 1—3 displayed inhibitory potential in a concentration-dependent manner against acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8) enzymes, respectively.
  • Fumiaki Kisa, Koji Yamada, Masafumi Kaneko, Masanori Inagaki, Ryuichi ...
    2005 年 53 巻 4 号 p. 382-386
    発行日: 2005年
    公開日: 2005/04/01
    ジャーナル フリー
    Five glucocerebroside molecular species, SJC-1-SJC-5, have been isolated from the less polar lipid fraction of a chloroform/methanol extract of the sea cucumber Stichopus japonicus. The structures of these glucocerebroside molecular species were determined on the basis of chemical and spectroscopic evidence. SJC-1, SJC-2, and SJC-3 are typical sphingosine- and phytosphingosine-type glucocerebroside molecular species with nonhydroxylated and hydroxylated fatty acyl moieties. SJC-4 and SJC-5 are also sphingosine-type glucocerebroside molecular species with hydroxylated fatty acyl moieties, although they are new glucocerebroside molecular species with unique sphingosine bases.
  • Hisashi Matsuda, Toshio Morikawa, Teruki Ohgushi, Tomoko Ishiwada, Nor ...
    2005 年 53 巻 4 号 p. 387-392
    発行日: 2005年
    公開日: 2005/04/01
    ジャーナル フリー
    The methanolic extract from the flowers of Angelica furcijuga KITAGAWA was found to inhibit nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages. From the methanolic extract, two new glycosides, hyuganosides IV and V, were isolated together with 28 known constituents. The structures of the new constituents were determined on the basis of chemical and physicochemical evidence. Furthermore, the inhibitory effects of 11 coumarin constituents on nitric oxide production were examined. Among them, 3′-angeloyl-cis-khellactone (IC50=82 μM), (S)-(−)-oxypeucedanin (57 μM), imperatorin (60 μM), isoepoxypteryxin (53 μM), and isopteryxin (8.8 μM) showed inhibitory activity.
  • Teppei Kumemura, Tominari Choshi, Aki Hirata, Mitsuko Sera, Yohhei Tak ...
    2005 年 53 巻 4 号 p. 393-397
    発行日: 2005年
    公開日: 2005/04/01
    ジャーナル フリー
    A total synthesis of a new furo[3,2-h]isoquinoline alkaloid TMC120-B (2), isolated from Aspergillus ustus together with two related compounds, has been completed in sixteen steps. The key step is the synthesis of the appropriate 3,7,8-trisubstituted isoquinoline framework (23) based on a thermal electrocyclic reaction of the 1-aza 6π-electron system involving the benzene double bond. In addition, the microwave assisted electrocyclic reaction of this system was newly performed.
  • Chisako Yamagami, Akira Hamasaki, Yukiko Kumagai, Tetsuhiro Moritoki, ...
    2005 年 53 巻 4 号 p. 398-401
    発行日: 2005年
    公開日: 2005/04/01
    ジャーナル フリー
    We recently proposed a new hydrogen-accepting scale, SHA, on the basis of the heat of formation calculated by the conductor-like screening model (COSMO) method. In this work, the same approach was applied to a series of compounds with a common hydrogen-donor group. Thus the SHA values for monosubstituted phenols were calculated and used for correlating their log Poct values (Poct: 1-octanol/water partition coefficient) with log PCL (PCL: chloroform/water partition coefficient) and log PE (PE: butyl ether/water partition coefficient). It was demonstrated that the SHA parameter works effectively, providing excellent correlations whose physicochemical meanings are well rationalized in terms of hydrogen-bonding characteristics of the substituents.
  • Isao Kinoyama, Nobuaki Taniguchi, Eiji Kawaminami, Eisuke Nozawa, Hiro ...
    2005 年 53 巻 4 号 p. 402-409
    発行日: 2005年
    公開日: 2005/04/01
    ジャーナル フリー
    A novel series of N-arylpiperazine-1-carboxamide derivatives was synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic properties were evaluated. Reporter assays indicated that trans-2,5-dimethylpiperazine derivatives are potent AR antagonists, and in this series trans-N-4-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,4-difluorophenyl)-2,5-dimethylpiperazine-1-carboxamide (18g, YM-175735) exhibited the most potent antiandrogenic activity. Compared to bicalutamide, YM-175735 is an approximately 4-fold stronger AR antagonist and has slightly increased antiandrogenic activity, suggesting that YM-175735 may be useful in the treatment of prostate cancer.
  • Seiji Miwatashi, Yasuyoshi Arikawa, Ken-ichi Naruo, Keiko Igaki, Yasum ...
    2005 年 53 巻 4 号 p. 410-418
    発行日: 2005年
    公開日: 2005/04/01
    ジャーナル フリー
    A novel series of 4-phenyl-5-pyridyl-1,3-thiazole analogues possessing potent in vitro inhibitory activity against p38 mitogen-activated protein kinase and the release of tumor necrosis factor-α (TNF-α) from human monocytic THP-1 cells stimulated by lipopolysaccharide has been identified. Subsequent structure–activity relationship (SAR) studies and optimization for absorption, distribution, metabolism, and elimination (ADME) profiles led to the identification of compounds 7g and 10b as orally active lead candidates that block the in vivo production of proinflammatory cytokine (TNF-α). In pharmacokinetic studies, compound 10b showed good oral administration in mice and demonstrated significant in vivo anti-inflammatory activity in an anti-collagen monoclonal antibody-induced arthritis mouse model (minimum effective dose (MED)=30 mg/kg). Further elucidation of this class of compounds may provide novel anti-inflammatory agents, such as anti-rheumatoid arthritis drugs.
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