Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
  • 67 巻 (2019) 9 号 p. 897-903
    Development of Diagnostic and Therapeutic Probes with Controlled Pharmacokinetics for Use in Radiotheranostics もっと読む

    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.

  • 67 巻 (2019) 9 号 p. 953-958
    Asymmetric Total Syntheses and Structure Elucidations of (+)-Eurotiumide F and (+)-Eurotiumide G もっと読む

    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.

  • 67 巻 (2019) 8 号 p. 733-771
    Development of Metal Nanoparticle Catalysis toward Drug Discovery もっと読む

    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.

  • 67 巻 (2019) 8 号 p. 872-876
    Synthesis of Propargylic Ethers by Gold-Mediated Reaction of Terminal Alkynes with Acetals もっと読む

    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.

  • 67 巻 (2019) 8 号 p. 877-883
    Study of the Inducible Cross-Linking Reaction to mRNA and the Effect on the Translation もっと読む

    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.

  • 67 巻 (2019) 7 号 p. 693-698
    Transition in Longgu Surface Associated with Decoction Process of Keishikaryukotsuboreito もっと読む

    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.

  • 67 巻 (2019) 7 号 p. 620-631
    Chemical Studies on Bioactive Natural Products Directed toward Development of Novel Antiinfective and Anticancer Medicines もっと読む

    Natural products are potential sources of lead compounds, especially intractable chemotherapeutic targets that require molecules with three-dimensional diversity rather than flatter “drug-like” molecules. This review article highlights the author’s efforts toward establishing synthetic routes to natural anti-tuberculosis and anti-tumor products, including structure−activity relationship studies. The synthetic targets, caprazamycin C, intervenolin, and leucinostatin A, exhibit striking biologic properties, such as antibacterial activity toward highly resistant strains of tuberculosis and interference with growth signals from stromal cells to tumor cells.

  • 67 巻 (2019) 7 号 p. 609-619
    Discovery of Nuclear Receptor Ligands and Elucidation of Their Mechanisms of Action もっと読む

    The author developed a series of vitamin D analogues which act as agonist, partial agonist, or antagonist for vitamin D receptor (VDR). The author examined the structures of the ligand-binding domain (LBD) of VDR complexed with the analogues by the X-ray crystal structural analysis, and small-angle X-ray scattering analysis combined with molecular dynamics simulation. All states of the VDR-LBD, which include agonist-, partial agonist- and antagonist-binding structures and apo-state structure, were clarified. Thus the author elucidated the mechanisms of VDR agonism, partial agonism, and antagonism based on structural changes (differences) in VDR-LBD induced by ligand binding.

  • 67 巻 (2019) 6 号 p. 566-575
    Design, Synthesis and Biological Evaluation of Novel Nonsteroidal Progesterone Receptor Antagonists Based on Phenylamino-1,3,5-triazine Scaffold もっと読む

    The novel progesterone receptor antagonists based on the multi-template approach were developed. Multi-template strategy enables facile structure-activity relationship (SAR) investigation, and phenylamino-1,3,5-triazine scaffold is a useful core structure for development of transcription modulators targeting nuclear receptors.

  • 67 巻 (2019) 6 号 p. 576-579
    In Cellullo and ex Vivo Availability of a Yellowish-Green-Light-Controllable NO Releaser もっと読む

    Light controllable compounds are very useful tools to manipulate biological signaling. In this paper, authors showed the biological applicability of a yellowish-green light controllable NO releaser, NO-Rosa5, which is more readily synthesizable and efficient NO releaser than its prototype, NO-Rosa1. NO-Rosa5 showed less toxicity in MTT assay than a blue light controllable NO releaser, NOBL-1, and was applicable to photoinduced NO release control in cellular condition. Furthermore, NO-Rosa5 could control vasodilation of rat aortic strip by light stimulation in Magnus test condition. NO-Rosa5 is expected to be useful chemical tool for NO research and utilized for innovative therapeutic method.

  • 67 巻 (2019) 6 号 p. 580-586
    T2 Relaxation Study to Evaluate the Crystalline State of Indomethacin Containing Solid Dispersions Using Time-Domain NMR もっと読む

    The aim of this study was to demonstrate the usefulness of T2 measurements conducted with a time-domain NMR (TD-NMR) for the characterization of active pharmaceutical ingredients (APIs) containing solid dosage forms. In the course of the experiments, the authors found that T2 measurements could detect the difference between the amorphous and crystalline API; furthermore, it was effective in monitoring the transformation from amorphous to crystalline during a thermal stress test. From these findings, the authors concluded that T2 measurement by TD-NMR is a promising analysis for the characterization of APIs in solid dosage forms, including SD-based pharmaceuticals.

  • 67 巻 (2019) 6 号 p. 587-593
    Direct Formylation of Fluorine-Containing Aromatics with Dichloromethyl Alkyl Ethers もっと読む

    Although fluorine-containing aryl formates have currently flourished as pharmaceutical and agrochemical intermediates, there is limited number of bearable methods in a large scale synthesis. In this article, the authors developed new operationally secure preparation method for dichloromethyl alkyl ethers having long carbon chains, and direct formylation of fluorine-containing aromatics with those reagents, which are applicable in a large scale synthesis. The authors also showed a number of examples for O-formylation of fluorine-containing and non-fluorine-containing aromatics with those reagents and the mechanistic aspect was discussed. The present method is simple and straightforward for laboratory and industrial use.

  • 67 巻 (2019) 6 号 p. 594-598
    Total Synthesis of 3-epi-Juruenolide C もっと読む

    This paper describes that the first total synthesis of 3-epi-Juruenolide C. The γ-lactone natural product, which was isolated from roots of Virola surinamensis, exhibits moderate antifungal activity against Cladosporium cladosporioides. The synthesis features a highly selective cross metathesis and the subsequent one-pot regioselective bromination, an intramolecular carbonylation using bis(triphenylphosphine)dicarbonylnickel, and a face-selective hydrogenation using a homogeneous Wilkinson’s catalyst. The sequential synthetic procedures could be useful to complete the synthetic and biological studies of other related γ-lactone natural products.

  • 67 巻 (2019) 5 号 p. 397-403
    Nickel-Catalyzed Hydrocyanation of Allenes and Its Application もっと読む

    Regioselective cyanation of simple and non-activated carbon–carbon bonds catalyzed by nickel complexes is described. This protocol enables to use of the substituted allenes for regio- and stereocontrolled transformations and their applications for cyclization, 3-component coupling reaction, heterocycle formation as well as natural product synthesis are demonstrated. The author reveals the origin of the above selectivity by axial chirality transfer process using optically active allenes as substrates. Steric bulk of substituents is found to be a key factor for discrimination of allenyl carbon–carbon double bonds in hydrometallation step.

  • 67 巻 (2019) 5 号 p. 439-444
    Measurement of Linezolid and Its Metabolites PNU-142300 and PNU-142586 in Human Plasma Using Ultra-Performance Liquid Chromatography Method もっと読む

    This paper describes the development and validation of a method for measuring linezolid and its metabolites PNU-142300 and PNU-142586 in human plasma, using ultra-performance liquid chromatography (UPLC) method. This method enables the simultaneous measurement of these three components within 3 min. Further, plasma concentrations of linezolid, PNU-142300 and PNU-142586 in patients treated with linezolid could be measured. The developed method is a useful tool for therapeutic drug monitoring and clinical pharmacokinetic/pharmacodynamic (PK/PD) profiling of linezolid, as well as for dose optimization during treatment.

  • 67 巻 (2019) 5 号 p. 461-466
    Study on Control of pH-Modulation Crystallization Utilizing Concept of Dissociation Equilibrium もっと読む

    3-Alkenyl cephem compound is a pharmaceutical intermediate. It is typically crystalized by pH adjustment method. However, since the filtration time in the solid-liquid separator is a bottleneck in the production, there is a need to control crystal morphology while changing the pH. This study could be shorten filtration time by pH-modulation operation that repeating the crystallization operation in the vicinity of solubility. The obtained monodisperse particles were like a pseudo-growth body in which a large number of primary particles were aggregated and increased, rather than being a crystallite growth.

  • 67 巻 (2019) 5 号 p. 476-480
    The Revised Structure of the Cyclic Octapeptide Surugamide A もっと読む

    Surugamide A, a non-ribosomal peptide with cathepsin B inhibitory activity, and its closely related derivatives, surugamides B-E are cyclic octapeptides produced by several Streptomyces species. All these peptides except for surugamide B contain a D-Ile residue that involve Cβ-epimerization step during its biosynthesis. However, the genes responsible for this conversion is absent in the biosynthetic gene cluster of surugamides. To clarify this issue, surugamide A containing D-Ile as well as its epimer having D-allo-Ile were synthesized. HPLC and Marfey’s analyses showed that surugamide A actually possesses D-allo-Ile instead of D-Ile, requiring structural collection of this group of peptides.

  • 67 巻 (2019) 4 号 p. 367-371
    A Simple and Easy Method of Monitoring Doxorubicin Release from a Liposomal Drug Formulation in the Serum Using Fluorescence Spectroscopy もっと読む

    In order to maximize the effect of drugs, nanomedicines, drug-containing nanoparticles, have become popular in the field of medicine as they allow selective delivery of drugs to the disease target. It is important to understand the drug release form nanomedicine at the disease target. In this study, the authors developed a simple and easy method of monitoring drug release from nanomedicine using a fluorescence analysis, especially fluorescence fingerprint. The authors used DOXIL as a typical nanomedicine and found out that the release of the encapsulated drug, doxorubicin, is accelerated by albumin which is the most abundant protein in the blood.

  • 67 巻 (2019) 4 号 p. 289-298
    Cyclodextrin-Based Molecular Accessories for Drug Discovery and Drug Delivery もっと読む

    A person may choose to wear an accessory so as to enhance their appearance and give them confidence and thus a change of character. So what happens when accessories are decorated with drugs? The author has developed molecular accessories for drugs through supramolecular chemistry to create new medicines and pharmaceutical technologies. In this article, the author introduces cyclodextrin-based supramolecular accessories such as molecular necklace, molecular earring, and intelligent molecular necklace, and describes their application in pharmaceutical sciences. Moreover, the author proposes a new concept in pharmaceutical sciences termed as “supramolecular pharmaceutical sciences,” which combines pharmaceutical sciences and supramolecular chemistry.

  • 67 巻 (2019) 3 号 p. 271-276
    A Time-Domain NMR Study of the State of Water in Wet Granules with Different Fillers and Its Contribution to the Wet Granulation Process and to the Characteristics of Granules もっと読む

    Wet granulation is one of the fundamental unit operations for manufacturing pharmaceutical solid dosage forms including tablets. This study investigated in detail the states of water incorporated in wet granules composed of different fillers. The key instrument to evaluate the state of water was a low-field benchtop 1H-NMR time-domain NMR (TD-NMR). This study successfully concluded that the state of water significantly affected the wet granulation process and the characteristics of the resultant granules. The findings can offer valuable knowledge on wet granulation process from the viewpoint of molecular mobility of water.