Kobayashi, Toi

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmaceutical Sciences (Shiba-Kyoritsu)

Position

Research Associate/Assistant Professor/Instructor
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Papers 【 Display / hide 】

  • In2Q2: A New Entry of 16-Membered Tetraazamacrocycle Concatenating Indole and Quinoline Units

    Kihara K., Kobayashi T., Xu W., Kumagai N.

    Chemistry - A European Journal 30 ( 25 )  2024.05

    ISSN  09476539

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    A new family of 16-membered macrocycles comprising two indole (In) and two quinoline (Q) units, coined In2Q2, was synthesized. Each unit is diagonally located and concatenated in a head-to-tail fashion, furnishing a non-flat saddle-shaped architecture with C2 symmetry. The synthetic protocol utilizing macrocyclic diamide as a pivotal precursor allowed us to access a series of In2Q2 derivatives bearing various substituents on the periphery. The In2Q2 derivatives and their Zn2+ complexes were emissive in both solution phase and solid state. While the entire architecture of In2Q2 is similar to that of quinoline tetramer TEtraQuinoline, a couple of contrasting physicochemical properties were revealed.

  • Oxa-TriQuinoline: A New Entry to Aza-Oxa-Crown Architectures**

    Kobayashi T., Kumagai N.

    Angewandte Chemie - International Edition 62 ( 32 )  2023.08

    ISSN  14337851

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    A new 15-membered-macrocyclic molecular entity, oxa-TriQuinoline (o-TQ), was designed and synthesized. In o-TQ, three oxygen atoms were joined onto three quinoline units at the 2- and 8-positions in a head-to-tail fashion by three-fold SNAr reactions, giving rise to the characteristic N3O3 aza-oxa-crown architecture. o-TQ can serve as a new tridentate nitrogen ligand to capture a CuI cation and adopt a bowl shape, before supramolecular complexation with corannulene and [12]cycloparaphenylene (CPP) occurs through π–π and CH–π interactions. In the presence of the CuI cation, the non-emissive o-TQ becomes a highly emissive material in the solid state, whereby the emission wavelengths depend on the ancillary ligand on the CuI cation. The o-TQ/CuI complex is able to promote carbene catalysis to provide a range of enamines with a gem-difluorinated terminus.

  • Peripheral Modification of Tripodal Aza-Oxa-Crown Oxa-TriQuinoline

    Kobayashi T., Sakurai T., Kumagai N.

    Bulletin of the Chemical Society of Japan 96 ( 10 ) 1139 - 1143 2023

    ISSN  00092673

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    Oxa-TriQuinoline (o-TQ) is a new entry in the collection of aza-oxa-crown compounds featuring a semi-rigid flexible conformation and a tripodal ligation capability through three quinoline units. Herein, we describe the installation of functional groups and aromatic substituents on the outer edge of o-TQ to modulate its physicochemical properties. Amino and bromo substituents were regioselectively introduced at the 5-position, forming bowl-shaped Cu(I) complexes in which three quinoline units coordinated to Cu(I). X-ray crystallography indicated that these o-TQ derivatives preferred an almost identical geometry in both the absence and presence of Cu(I). In contrast to o-TQ, some new o-TQ derivatives exhibited photoluminescent properties in solution and/or in the solid state depending on the substituents.

  • Novel pyridinium-type fullerene derivatives as multitargeting inhibitors of HIV-1 reverse transcriptase, HIV-1 protease, and HCV NS5B polymerase

    Kobayashi T., Yasuno T., Takahashi K., Nakamura S., Mashino T., Ohe T.

    Bioorganic and Medicinal Chemistry Letters 49 2021.10

    ISSN  0960894X

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    In the present study, we newly synthesized four types of novel fullerene derivatives: pyridinium/ethyl ester-type derivatives 3b−3l, pyridinium/carboxylic acid-type derivatives 4a, 4e, 4f, pyridinium/amide-type derivative 5a, and pyridinium/2-morpholinone-type derivative 6a. Among the assessed compounds, cis-3c, cis-3d, trans-3e, trans-3h, cis-3l, cis-4e, cis-4f, trans-4f, and cis-5a were found to inhibit HIV-1 reverse transcriptase (HIV-RT), HIV-1 protease (HIV-PR), and HCV NS5B polymerase (HCV NS5B), with IC50 values observed in the micromolar range. Cellular uptake of pyridinium/ethyl ester-type derivatives was higher than that of corresponding pyridinium/carboxylic acid-type derivatives and pyridinium/amide-type derivatives. This result might indicate that pyridinium/ethyl ester-type derivatives are expected to be lead compounds for multitargeting drugs to treat HIV/HCV coinfection.

  • Fullerene derivatives as dual inhibitors of HIV-1 reverse transcriptase and protease

    Yasuno T., Ohe T., Kataoka H., Hashimoto K., Ishikawa Y., Furukawa K., Tateishi Y., Kobayashi T., Takahashi K., Nakamura S., Mashino T.

    Bioorganic and Medicinal Chemistry Letters 31 2021.01

    ISSN  0960894X

    　View Summary

    In the present study, we newly synthesized three types of novel fullerene derivatives: pyridinium-type derivatives trans-3a and 4a-5b, piperidinium-type derivative 9, and proline-type derivatives 10a-12. Among the assessed compounds, 5a, 10e, 10f, 10i, 11a-d, and 12 were found to inhibit both HIV reverse transcriptase and HIV protease (HIV-PR), with IC50 values in the low micromolar range being observed. Regarding HIV-PR inhibition activity, proline-type derivatives 11a-11d and 12, bearing an alkyl chain between the hydroxylmethylcarbonyl (HMC) moiety and pyrrolidine ring, were more potent than other derivatives. This result might indicate that connecting HMC moieties with proline-type fullerene derivatives through properly sized alkyl chain leads to improved HIV-PR inhibitory activity.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Courses Taught 【 Display / hide 】

  • DRUG SYNTHESIS LABORATORY COURSE

    2025

  • CHEMISTRY OF BIOACTIVE SUBSTANCES

    2025

  • BACHELOR'S THESIS

    2025

  • EARLY EXPOSURE TO INDUSTRY

    2025

  • STUDY OF MAJOR FIELD (MOLECULAR DESIGN)

    2025

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