Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Featured articles
Displaying 221-220 of 255 articles
  • Volume 66 (2018) Issue 2 Pages 116
    Foreword Read more
    Editor's pick

    Nucleosides and nucleotides have fascinated chemists and biologists, because nucleosides and nucleotides are of vital importance not only as components of ribo- and deoxyribonucleic acids in central dogma, but also as a wide variety of biofunctional molecules. This current topic summarized the recent progress on chemical ligation of oligonucleotides, nucleoside antibiotics, unnatural base pairs, antiviral/antitumor nucleoside analogues, protecting groups for oligonucleotide prodrugs, and nucleotide second messengers.

  • Volume 66 (2018) Issue 2 Pages 105-115
    Synthetic Studies on Heteropolycyclic Natural Products: Development of Divergent Strategy Read more
    Editor's pick

    Three divergent total syntheses of heteropolycyclic natural product groups, namely gelsedine-type alkaloids, amathaspiramide alkaloids, and erythrina alkaloids, are outlined. These syntheses employed the strategy for designing a late-stage pluripotent common synthetic intermediate that is prepared via the formulation of original and innovative transformations. Brief description of the philosophy and criteria for choosing synthetic targets and common synthetic precursors, as well as the details of development of the overall synthetic schemes mapped around the designed common intermediate are discussed.

  • Volume 66 (2018) Issue 1 Pages 84-95
    Solid-Phase Modular Synthesis of Park Nucleotide and Lipids I and II Analogues Read more
    Editor's pick

    The paper describes solid-phase synthesis of peptidoglycan biosynthesis precursor and its analogues: Park nucleotide (1), neryl-lipid I (2) and neryl-lipid II (3). The higher acidity of activators accelerated the reaction rate of diphosphate formation, and solid-phase diphosphate formation was accomplished by using triazolium triflate (29) as an activator. The synthetic strategy enables to prepare 1-3 in a short time with a single purification. These analogues could be useful as chemical probes for discovering novel antibacterial agent and elucidating mechanistic studies.



  • Volume 66 (2018) Issue 1 Pages 78-83
    Secoiridoid Glycosides from the Twigs of Ligustrum obtusifolium Possess Anti-inflammatory and Neuroprotective Effects Read more
    Editor's pick

    This study showed that secoiridoid glycosides are the main constituents of the twigs of L. obtusifolium, and two new secoiridoid derivatives, obtusifoliside A and B (1, 2), were isolated from this plant. Moreover, anti-inflammatory, and neuroprotective activities of the isolated compounds were investigated. Among the isolates, the new compound 2 showed remarkably better anti-inflammatory effects without cell toxicity. This study could be useful for the development of novel anti-inflammatory and neuroprotective agents.



  • Volume 66 (2018) Issue 1 Pages 20
    Foreword Read more
    Editor's pick

    Technological progress in medicinal chemistry has contributed to develop a variety of drug candidates in pharmaceuticals. Focusing on the significant progress in the fields shown in the cover, the present current topics include three reviews, “New Gateways to Platinum Group Metal-Catalyzed Direct Deuterium-Labeling Method Utilizing Hydrogen as a Catalyst Activator,” “7-Azaindole: A Versatile Scaffold for Developing Kinase Inhibitors” and “Discovery and Development of Muscarinic Acetylcholine M4 Activators as Promising Therapeutic Agents for CNS Diseases” and one communication, “A Peptide–Glycolipid Interaction Probed by Retroinverso Peptide Analogues.”



  • Volume 66 (2018) Issue 1 Pages 1-19
    Creation of Novel Toxic Gas Surrogates and the Development of Safe and Facile Catalytic Reactions Read more
    Editor's pick

    Utilization of toxic gas surrogates can contribute to improving the safety and practicality for implementation of synthetic organic reactions. This review describes the author’s discovery, development, and applications of toxic gas surrogates. Various carbonyl compounds were obtained by Pd-catalyzed carbonylative transformations under mild conditions using novel carbon monoxide (CO) surrogates. Mechanistic studies of the CO generation and gram-scale syntheses using CO surrogates were successfully performed. Furthermore, the use of an inexpensive sulfur dioxide surrogate led to the development of unprecedented selective syntheses of sulfonamides and sulfinamides.



  • Volume 65 (2017) Issue 12 Pages 1099-1112
    Development of Highly Sensitive Analytical Methods for Biologically Relevant Materials and Their Pharmaceutical Applications Read more
    Editor's pick

    Analytical methods for disease diagnosis require high sensitivity and specific methods. For neonatal mass screening of congenital metabolic disorders, a 3 mm diameter disc of dried filter paper blood obtained from one drop of newborn blood is used, and one disc contains about 4 μL of blood. Diagnosis is performed by measuring hormones and genes in this disc. In hormone analysis, chemiluminescent enzyme immunoassay was developed. In genetic analysis, pyrophosphate generated by PCR amplification reaction or DNA fragment as amplification product was analyzed by luciferase bioluminescence method and capillary electrophoresis, respectively. In addition, identification of reactive oxygen species generated from natural medicines and antianginal drugs and their physiological action mechanism are described.

  • Volume 65 (2017) Issue 12 Pages 1167-1174
    Synthesis of Tetrahydrobiphenylene via Pd(0)-Catalyzed C(sp2)–H Functionalization Read more
    Editor's pick

    This paper describes the development of a synthetic method for tetrahydrobiphenylenes and derivatives based on a palladium(0)-catalyzed C(sp2)−H functionalization. This is a new direct method for accessing partially hydrogenated biphenylenes. The derivatization of a tetrahydrobiphenylene is also reported.

  • Volume 65 (2017) Issue 12 Pages 1144-1160
    Novel Non-carboxylate Benzoylsulfonamide-Based Protein Tyrosine Phosphatase 1B Inhibitors with Non-competitive Actions Read more
    Editor's pick

    A novel series of benzoylsulfonamide derivatives were synthesized and biologically evaluated. Among them, compound 18K was shown to inhibit protein tyrosine phosphatase 1B (PTP1B) activity potently and non-competitively (IC50=0.25 μM). Molecular dynamics simulation demonstrated that 18K binds to the allosteric site of PTP1B. Compound 18K showed high oral absorption in mice, rats, and beagles, and markedly reduced plasma glucose levels, TG levels, and HOMA values with no side effects at 30 mg/kg (p.o.) for one week in db/db mice. In conclusion, the substituted benzoylsulfonamide is a novel scaffold of non-competitive allosteric PTP1B inhibitors, and compound 18K is a promising candidate for an efficacious and safe anti-diabetic drug with anti-obesity effects.

  • Volume 65 (2017) Issue 11 Pages 1058-1077
    Discovery of a Novel Series of Pyrazolo[1,5-a]pyrimidine-Based Phosphodiesterase 2A Inhibitors Structurally Different from N-((1S)-1-(3-Fluoro-4-(trifluoromethoxy)phenyl)-2-methoxyethyl)-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915), for the Treatment of Cognitive Disorders Read more
    Editor's pick

    This article describes the discovery of a new class of lead compound 5 by combining structural features from previously disclosed two chemotypes, represented by 3 and 4, and subsequent medicinal chemistry efforts to optimize potency, PDE selectivity, and other preclinical properties including in vitro phototoxicity and in vivo rat plasma clearance. These efforts culminated in the identification of 20, which demonstrated significant elevation of cGMP levels in rat brains, and moreover, attenuated MK-801-induced episodic memory deficits in a passive avoidance task in rats. These data provide further support to the potential therapeutic utility of PDE2A inhibitors in enhancing cognitive performance.

  • Volume 65 (2017) Issue 11 Pages 1051-1057
    Novel Non-steroidal Progesterone Receptor Ligands Based on m-Carborane Containing a Secondary Alcohol: Effect of Chirality on Ligand Activity Read more
    Editor's pick

    The authors designed and synthesized m-carborane-based secondary alcohols and investigated their PR-ligand activity. All the synthesized alcohols exhibited PR-antagonistic activity at subnanomolar concentration. Among them, alcohols having a small alkyl side chain and a 4-cyanophenyl group, such as 7a, also exhibited PR-agonistic activity in a relatively high concentration range. Optical resolution of secondary alcohols having a methyl side chain was performed, and the PR-ligand activity and PR-binding affinity of the purified enantiomers were examined. The chirality of the secondary alcohol appears to have a more significant influence on PR-agonistic activity than on antagonistic activity.

  • Volume 65 (2017) Issue 11 Pages 1035-1044
    Gelation Factors of Pectin for Development of a Powder Form of Gel, Dry Jelly, as a Novel Dosage Form Read more
    Editor's pick

    Jellies for oral administration are dosage forms that contain water and heat is generally applied to the jellies during the manufacturing process. Therefore, it is difficult to formulate drugs that may be affected adversely by water and/or heat. To solve this problem, the authors develop a powder form of gel as a novel dosage form (dry jelly) that is converted to gel after addition of water at the time of administration. The concept of dry jelly gelation by water addition is shown in graphical abstract. In the article, the critical factors affecting gelation phenomena as well as physical and drug dissolution properties of the gel prepared from drug-containing dry jelly are evaluated.


  • Volume 65 (2017) Issue 11 Pages 1028-1034
    Effect of Magnesium Stearate Mono- and Dihydrate Dispersibilities on Physical Properties of Tablets Read more
    Editor's pick

    Magnesium stearate (MgSt), an essential lubricant in the manufacturing of tablets, is available in several hydrate forms with different qualities that affect the physical properties of tablets. This article examined MgSt mono- and dihydrates, and their effects on tablet dissolution, disintegration, and hardness were examined in terms of surface free energy and dispersibility. It was found that changes in those parameters related to dispersibility and dissolution differed between MgSt hydrates. This suggests that the quantitative determination of dispersibility of MgSt using NIR-CI is a useful methodology for improving the understanding of tablet manufacturing blending processes.

  • Volume 65 (2017) Issue 10 Pages 967-972
    Prediction of Dissolution Data Integrated in Tablet Database Using Four-Layered Artificial Neural Networks Read more
    Editor's pick

    A four-layered artificial neural network (4LNN) was employed to predict dissolution data from physicochemical and powder properties of active pharmaceutical ingredients (APIs) formulated in various kinds of tablets. Causal factors of APIs in the input layer were simplified into the nodes in the 1st hidden layer, properly integrated information would then be transferred to the nodes in the 2nd hidden layer, and finally the secured outcome was delivered in the output layer. An excellent model for the prediction of dissolution data was achieved with 4LNN method. The function of 4LNN was appreciably better than that of conventional three-layered model.

  • Volume 65 (2017) Issue 10 Pages 950-958
    Design, Synthesis and Antiproliferative Evaluation of Novel Disulfides Containing 1,3,4-Thiadiazole Moiety Read more
    Editor's pick

    In the article, a series of novel disulfides containing 1,3,4-thiadiazole moiety were synthesized and evaluated for their in vitro antiproliferative activities using CCK-8 assay against human cancer cell lines A549, HeLa, SMMC-7721 and normal cell lines L929. The bioassay results indicated that most of the tested compounds exhibited antiproliferation with different degrees, and some compounds inhibited the proliferation better than positive control 5-fluorouracil against various cancer cell lines. Furthermore, all compounds showed weak cytotoxic effect against L929 cells. Therefore, the results suggest that the substituent groups are vital for improving the potency and selectivity of this class of compounds.

  • Volume 65 (2017) Issue 10 Pages 945-949
    Rapid Analysis of DOXIL Stability and Drug Release from DOXIL by HPLC Using a Glycidyl Methacrylate-Coated Monolithic Column Read more
    Editor's pick

    The authors described that membrane-permeable bases accelerated the release of encapsulated drug, doxorubicin, from DOXIL by using a HPLC column for nanomedicine analysis.

  • Volume 65 (2017) Issue 10 Pages 940-944
    Versatile Amine-Promoted Mild Methanolysis of 3,5-Dinitrobenzoates and Its Application to the Synthesis of Colorado Potato Beetle Pheromone Read more
    Editor's pick

    In the article, a mild deacylation method for 3,5-dinitrobenzoates, which are often used to improve their diastereomeric or enantiomeric purities by recrystallization and also widely used as a pro-nucleophile in the Mitsunobu reaction, has been developed by using methanolic solutions of amines, such as dialkylamines. Removal of dinitrobenzoyl groups undergoes without affecting existing acetyl groups and also without affecting stereochemistry in α-hydroxy ketone. Encouraged by the promising versatility, the authors successfully applied this method to the efficient asymmetric synthesis of Colorado potato beetle pheromone.

  • Volume 65 (2017) Issue 10 Pages 930-939
    Microtropins Q–W, ent-Labdane Glucosides: Microtropiosides G–I, Ursane-Type Triterpene Diglucoside and Flavonol Glycoside from the Leaves of Microtropis japonica Read more
    Editor's pick

    Since an antileukemic ansa macrolide, maytansine was first isolated from Maytenus ovata, plants belong to Celastraceae draw the attention of natural product chemists. The authors focused on the plants collected in Okinawa Islands, and Celastraceae plant, Microtropis japonica was chosen for the target material. ent-Labdane glycoside and 6'-O-(2"S,3R")-2"-ethyl-2",3"-dihydroxybutyrates of aliphatic alcohol β-D-glucosides branches have been isolated from leaves and branches respectively. Current investigation of leaves afforded further ent-labdane glucosides, 6'-O-2"-ethyl-2",3"-dihydroxybutyrates of aliphatic alcohol β-D-glucosides, ursane-type triterpene diglucoside, and flavonol glycoside.

  • Volume 65 (2017) Issue 9 Pages 862-868
    Ethereal C–O Bond Cleavage Mediated by Ni(0)-Ate Complex: A DFT Study Read more
    Editor's pick

    Density functional theory calculations were performed to explore the mechanism of Ni-catalyzed cross-coupling reactions involving organo-lithium and -zinc reagents though ethereal C–O bond cleavage. In comparison with our previous mechanistic study on etheric Kumada–Tamao reaction, it shows that the the Ni(0)-ate complex-mediated reaction pathway is a new and general mechanism for ethereal cross-coupling reactions, which can well explain the experimental findings for several ethereal C–O bond cleavage couplings.  The present work also suggests that the anionic character of organometallic nucleophiles can change oxidative addition mechanisms/pathways, which may provide new reactivity and selectivity.



  • Volume 65 (2017) Issue 9 Pages 848-853
    Effect of the External Lubrication Method for a Rotary Tablet Press on the Adhesion of the Film Coating Layer Read more
    Editor's pick

    We evaluated the adhesion force of the film coating layer to the surface of tablets prepared using an external lubrication method. Increasing lubrication decreased wettability of the tablet surface. However, no change was observed in the adhesion force of the film coating layer. The magnesium stearate distribution state on the tablet surface was assessed and the lubricant was uniformly dispersed in the external lubrication samples. The distribution state of the lubricant affects the adhesion force of the film coating layer, and external lubrication maintained sufficient lubricity and adhesion force of the film coating layer with a small amount of lubricant.



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