Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Featured articles
Showing 81-80 articles out of 199 articles
  • Volume 68 (2020) Issue 1 Pages 34-45
    Drug Discovery Researches on Modulators of Lysine-Modifying Enzymes Based on Strategic Chemistry Approaches Read more
    Editor’s picks

    Because lysine modifications on proteins control various cellular processes and aberrations of the modifications are associated with various diseases, chemical modulation of lysine-modifying enzymes is interesting as a method to regulate the cellular functions or as a therapeutic strategy. Therefore, the author has identified some modulators of lysine-modifying enzymes. To find the modulators, the author has combined conventional drug design with “strategic chemistry approaches,” such as drug design based on enzyme catalytic mechanism. In this review, the author’s drug discovery studies are presented.

  • Volume 68 (2020) Issue 1 Pages 77-90
    Discovery of 3,5-Dimethylpyridin-4(1H)-one Derivatives as Activators of AMP-Activated Protein Kinase (AMPK) Read more
    Editor’s picks

    This paper describes that synthesis and evaluation of novel 3,5-dimethylpyridin-4(1H)-one scaffold compounds as indirect AMP-activated protein kinase (AMPK) activators. Unlike direct AMPK activators, this series of compounds inhibited cell growth of MDA-MB-453 but not that of SK-BR-3. The initial structure optimization of the lead compound 4a led to the discovery of compound 4f with potent AMPK activation activity and poor aqueous solubility. By further optimizing 4f, promising compound 25 was found out as a potent AMPK activator with good aqueous solubility.

  • Volume 68 (2020) Issue 1 Pages 100-102
    Morphometric Analysis of Paramylon Particles Produced by Euglena gracilis EOD-1 Using FIB/SEM Tomography Read more
    Editor’s picks

    Euglena gracilis EOD-1, produces large quantities of paramylon, has been reported to function as a dietary fiber. However, the morphometric analysis of paramylon has not been conducted so far. The authors attempted to observe the detailed three-dimensional structure of paramylon by FIB/SEM. The inside of paramylon particles was comprised of a dense structure with no evidence of the presence of large pores and gaps. The specific surface area of paramylon particles was not as large as activated charcoal, but similar to those of plant starches, indicating that the cholesterol-lowering effect of paramylon cannot be simply attributed to its adsorption ability.

  • Volume 67 (2019) Issue 12 Pages 1259-1270
    Metal-Free Oxidative Cross-Coupling Reaction of Heteroaromatic and Related Compounds Read more
    Editor’s picks

    The ubiquity of the biaryls with heteroatoms in and on the rings, are of importance in organic chemistry as building blocks of functional compounds, such as bioactive natural products, pharmaceuticals, and chemicals. Therefore, the cross-couplings can provide powerful tools for the construction of biaryls and the development of a novel coupling method has been intensively studied by synthetic chemists. In the present study, the author demonstrated the metal-free oxidative couplings of two different aromatic C-H bonds in electron-rich arenes for producing biaryls based on new strategies and concepts using hypervalent iodine reagents.

  • Volume 67 (2019) Issue 12 Pages 1301-1313
    Comparative Study of Pharmacopoeias in Japan, Europe, and the United States: Toward the Further Convergence of International Pharmacopoeial Standards Read more
    Editor’s picks

    Pharmacopoeias have provided public standards to help ensure the quality of drugs. As of 2018, pharmacopoeias exist in 56 countries and 3 regions. These pharmacopoeias have contributed to the quality assurance of drug substances and products by providing common standards for users in each region/country. As drug markets and supply chain is globalizing, the independent standards in each pharmacopoeia increase users’ burden of having to perform analytical procedures in different ways and using different acceptance criteria to satisfy pharmacopoeia requirements that vary across regions. To contribute to the further convergence of pharmacopoeial standards, the authors conducted a comparative study of the pharmacopoeias in Japan, Europe, and the United States.

  • Volume 67 (2019) Issue 12 Pages 1337-1346
    Ebenamariosides A–D: Triterpene Glucosides and Megastigmanes from the Leaves of Diospyros maritima Read more
    Editor’s picks

    Four new triterpene glucosides and two megastigmanes were isolated from the leaves of Diospyros maritima. The structures of triterpene glucosides were elucidated by a sequential hydrolysis of glycosidic and ester bonds using different enzymes to give partial hydrolyzed intermediates and finally aglycones. Hydrolysis of 28-O-ester bonded glucose by a crude glucosidase may give a new tool in triterpene chemistry.  Two new megastigmanes were also isolated and their structures were unambiguously elucidated using the modified Mosher's method and two megastigmanes were chemically correlated by NaBH4 reduction of the ketonic one.

  • Volume 67 (2019) Issue 11 Pages 1171-1178
    Development of Chemical Biology Tools Focusing on Peptide/Amide Bond Cleavage Reaction Read more
    Editor’s picks

    Elucidation of functions of endogenous peptides/proteins is undoubtedly valuable because they are key players of most of biological pathways. The author has developed chemical biology tools to accelerate the functional elucidation from the viewpoint of synthetic organic chemistry. In this Featured Article, the author introduces following three tools invented by his group: 1) an artificial amino acid that enables stimulus-responsive functional control of peptides and proteins; 2) a traceable linker for facile identification of target proteins of bioactive ligands; 3) an in-cell compatible labeling reagent of proteins of interest.

  • Volume 67 (2019) Issue 11 Pages 1179-1182
    Deprotonative Coupling of Pyridines with Aldehydes Catalyzed by an HMDS-Amide Base Generated in Situ Read more
    Editor’s picks

    Deprotonative coupling of pyridines with electrophiles using a stoichiometric amount of strong Brønsted bases usually employs cryogenic conditions in order to inhibit the occurrence of side-reactions. In this paper, the authors established the efficient and convenient coupling reaction of 3,5-dihalopyridines and 3-chloro-5-(trifluoromethyl)pyridine using an HMDS-amide base generated in situ from a catalytic amount of CsF and a stoichiometric amount of N(TMS)3. The reaction proceeds under ambient conditions and demonstrates the applicability of various (hetero)arylaldehydes, pivalaldehyde, and cyclohexanecarboxaldehyde as an electrophile.

  • Volume 67 (2019) Issue 11 Pages 1183-1190
    Significance of Data Selection in Deep Learning for Reliable Binding Mode Prediction of Ligands in the Active Site of CYP3A4 Read more
    Editor’s picks

    A data science methodology to identify the correct binding mode between CYP3A4 and compounds using deep learning has been developed. The methodology enables us to predict the biding mode between a substrate and CYP3A4 whose binding mode is difficult to predict with conventional docking algorithms and binding mode scores mainly due to the larger and more flexible biding pocket than that of the other CYPs.


  • Volume 67 (2019) Issue 11 Pages 1242-1247
    Structural Analysis of Polygalaxanthones, C-Glucosyl Xanthones of Polygala tenuifolia Roots Read more
    Editor’s picks

    To guarantee the quality of crude drugs, the marker constituents for quality control corresponding to each crude drug are defined. A standard product with a fixed structure is indispensable for quality control of crude drugs, but the structure of the standard product is unclear in a few cases. The authors found multiple standards for polygalaxanthone III, which is a component of Onji's marker constituent for quality control, and concluded from NMR and MS/MS spectral analyses that their structures were polygalaxanthone III and polygalaxanthone XI. In this study, they propose the use of LC-MS/MS to distinguish polygalaxanthone III and XI.

  • Volume 67 (2019) Issue 10 Pages 1046-1049
    Lewis Base Assisted Lithium Brønsted Base Catalysis: A New Entry for Catalytic Asymmetric Synthesis of β2,2-Amino Acids Read more
    Editor’s picks

    A new catalytic system comprising chiral Ag Lewis acid and lithium Brønsted base is developed for the synthesis of β2,2-amino acids by direct Mannich-type reaction of isoxazolidin-5-ones. Two nitrogen atoms in the product are chemically distinctive and can be easily differentiated. The cover art illuminates these features of this work by a projection onto a mysterious space.

  • Volume 67 (2019) Issue 10 Pages 1131-1138
    Development of a Membrane Curvature-Sensing Peptide Based on a Structure–Activity Correlation Study Read more
    Editor’s picks

    Membrane curvature is involved in variety of cellular phenomena. Peptide-based sensors are useful that easily detect or visualize membrane curvatures in cell-related studies. These have advantages over protein-based sensors in terms of the compactness with smaller steric hindrance in their target recognition and the capabilities of chemical modification and easy handling. In this article, a structure–activity correlation study by the authors has led to an amphipathic peptide FAAV that recognizes high-curvature membranes. The FAAV may be a promising prototype of curvature sensors, which enable the capture of the dynamics and roles of membrane curvatures in our life.

  • Volume 67 (2019) Issue 10 Pages 1139-1143
    Non-naturally Occurring Helical Molecules Can Interfere with p53–MDM2 and p53–MDMX Protein–Protein Interactions Read more
    Editor’s picks

    a-Helix-a-helix interactions are frequently observed at protein-protein interfaces, and the p53-MDM2/MDMX interaction is considered to involve interactions between a-helix structures of p53 and MDM2/MDMX. This work showed herein even non-naturally occurring artificial helix of bicyclic β-proline oligomer derivatives, bearing pitch and diameter per turn different from the typical a-helix structure of a-amino acid peptides can mimic α-helix structure sufficiently to interfere with the p53-MDM2/MDMX interaction.

  • Volume 67 (2019) Issue 10 Pages 1152-1159
    Controlled-Release Fine Particles Prepared by Melt Adsorption for Orally Disintegrating Tablets Read more
    Editor’s picks

    The design of controlled-release particles is required for developing orally disintegrating tablets (ODT). The authors have focused on melt adsorption technique which affords precise control of the size distribution of controlled-release particles and requires neither solvents nor drying processes. In the present study, the authors demonstrated that melt adsorption is a superior manufacturing method for controlled-release particles. Specifically, ODT with adequate strength and disintegration could be prepared by using the particles which have been optimized by Design of Experiment (DoE) and Multiple regression analysis without losing sustained-release. This technique should contribute to the development of ODT to improve medication adherence.

  • Volume 67 (2019) Issue 9 Pages 897-903
    Development of Diagnostic and Therapeutic Probes with Controlled Pharmacokinetics for Use in Radiotheranostics Read more
    Editor’s picks

    Radiotheranostics means the integration between diagnosis and therapy using radioisotopes. In the radiotheranostics, the diagnostic probe and corresponding therapeutic probe should show similar biodistribution. Thus, imaging using diagnostic probes before therapy can predict therapeutic and side effects of corresponding therapeutic probes. The author has developed radiolabeled probes with controlled pharmacokinetics for use in radiotheranostics. In this article, bone-seeking probes, sigma-1 targeted probes, and αVβ3 integrin targeted probes containing RGD peptide for cancer diagnosis and therapy are introduced as radiotheranostic probes.

  • Volume 67 (2019) Issue 9 Pages 953-958
    Asymmetric Total Syntheses and Structure Elucidations of (+)-Eurotiumide F and (+)-Eurotiumide G Read more
    Editor’s picks

    Determining the stereochemistry of a cyclic acetal moiety is sometimes difficult because it is hard to observe NOESY correlations depending on the substitution pattern and the conformation. While the X-ray crystallographic analysis is a powerful method for structure determination, many natural products are often difficult to form single crystals because of their limited availability. The authors accomplished the first asymmetric total syntheses of (+)-eurotiumide F and (+)-eurotiumide G having such a cyclic acetal moiety, and through their total syntheses, they succeeded to measure the X-ray crystallographic analysis of eurotiumide G and revised the relative configuration between H1 and H4.

  • Volume 67 (2019) Issue 8 Pages 733-771
    Development of Metal Nanoparticle Catalysis toward Drug Discovery Read more
    Editor’s picks

    A methodologically and conceptually novel immobilization method to prepare metal nano-particles (NPs) catalyst are currently required for the development of organic, inorganic, green, materials, and medicinal chemistry. Here the authors developed” “in situ metal NP and nanospace simultaneous organization (PSSO) method”, which is different from previously reported metal NPs-immobilizing methods. They also applied the in situ PSSO method to prepare various immobilized transition-metal NPs, including base metals. For example, the in situ PSSO method can be applicable to easily prepare Pd, Ru, Ni, and Fe NPs with good recyclability and low metal leaching for use in organic synthesis.

  • Volume 67 (2019) Issue 8 Pages 872-876
    Synthesis of Propargylic Ethers by Gold-Mediated Reaction of Terminal Alkynes with Acetals Read more
    Editor’s picks

    Gold catalysts have attracted considerable attentions due to their low catalyst loading and the high functional group compatibility. The authors conducted an extensive research on the gold-catalyzed introduction of terminal alkynes to acetals to reveal that thermally stable cationic gold catalysts bearing bulky ligands were particularly suitable for the reaction. Because of its high utility to synthesize a broad range of propargylic ethers, this protocol should find a widespread use for synthesis of various propargylic ethers in the area of chemical biology and medicinal chemistry.

  • Volume 67 (2019) Issue 8 Pages 877-883
    Study of the Inducible Cross-Linking Reaction to mRNA and the Effect on the Translation Read more
    Editor’s picks

    The covalent bond formation (crosslinking) of mRNA with the antisense oligonucleotide promotes the translational inhibition. In this study, several derivatives of T-vinyl (4-vinylpyrimidin-2-one) were investigated to obtain the stable derivative so that its reactivity is protected until it access to the target site. Thus, the 2-thiopyrimidinyl T-vinyl derivatives was determined to be a good cross-linking agent with a moderate stability. The investigation using the Luc mRNA, the synthetic mRNA and non-cellular translation system revealed that the translation is terminated at the end of the cross-linked duplex between the mRNA and the oligonucleotide.

  • Volume 67 (2019) Issue 7 Pages 693-698
    Transition in Longgu Surface Associated with Decoction Process of Keishikaryukotsuboreito Read more
    Editor’s picks

    Longgu is a fossil crude drug used in Kampo prescriptions, but its role in the decoction is still unclear. The authors hypothesized that it adsorbs foreign organic compounds into its superficial pores, and aimed to reveal it indirectly by 1H magic angle spinning NMR spectroscopic analysis, thermogravimetric analysis and nitrogen adsorption isotherm. These analyses revealed that longgu was macroporous material, and it adsorbed organic compounds during the decoction process. Although further study is required, the authors suggest that the significance of longgu is in adjusting the component profiles in Kampo decoctions as an adsorbent.




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