Hiroyuki Kakei

Design and synthesis of 6-methylpyridin-2-one derivatives as novel and potent GluN2A positive allosteric modulators for the treatment of cognitive impairment

Takafumi Yukawa, Toshihiro Imaeda, Hiroyuki Kakei, Shogo Hashizume et autres

N-Methyl-D-aspartate receptors (NMDARs) are key regulators of synaptic plasticity in the central nervous system. Potentiation of NMDARs containing GluN2A subunit has been recently recognized as a promising therapeutic approach for neurological disorders. We identified a novel series of GluN2A positive allosteric modulator …

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Light-driven Radical-polar Crossover Catalysis Enabling Decarboxylative Fluorination of Redox Active Esters

Yunosuke Takekawa, Taiga Kodo, Kazunori Nagao, Hiroyuki Kakei et autres

This manuscript represents an organophotoredox-catalyzed decarboxylative fluorination of alkyl redox active esters with triethylamine trihydrofluoride. The reaction proceeds through a radical-polar crossover mechanism to generate a carbocation equivalent under non-acidic and transition metal free conditions. This protocol allows delivery of various tertiary …

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Design and synthesis of fused bicyclic inhibitors targeting the L5 loop site of centromere-associated protein E

Takaharu Hirayama, Masanori Okaniwa, Hiroshi Banno, Hiroyuki Kakei et autres

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CCDC 1439418: Experimental Crystal Structure Determination

Takaharu Hirayama, Masanori Okaniwa, Hiroshi Banno, Hiroyuki Kakei et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

Synthetic Studies on Centromere-Associated Protein-E (CENP-E) Inhibitors: 2. Application of Electrostatic Potential Map (EPM) and Structure-Based Modeling to Imidazo[1,2-a]pyridine Derivatives as Anti-Tumor Agents

Takaharu Hirayama, Masanori Okaniwa, Hiroshi Banno, Hiroyuki Kakei et autres

To develop centromere-associated protein-E (CENP-E) inhibitors for use as anticancer therapeutics, we designed novel imidazo[1,2-a]pyridines, utilizing previously discovered 5-bromo derivative 1a. By site-directed mutagenesis analysis, we confirmed the ligand binding site. A docking model revealed the structurally important molecular features for effective …

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CCDC 1037305: Experimental Crystal Structure Determination

Takaharu Hirayama, Masanori Okaniwa, Hiroshi Banno, Hiroyuki Kakei et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

CCDC 1037306: Experimental Crystal Structure Determination

Takaharu Hirayama, Masanori Okaniwa, Hiroshi Banno, Hiroyuki Kakei et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

Design and Synthesis of Potent Inhibitor of Apoptosis (IAP) Proteins Antagonists Bearing an Octahydropyrrolo[1,2-a]pyrazine Scaffold as a Novel Proline Mimetic

Kentaro Hashimoto, Bunnai Saito, Naoki Miyamoto, Yuya Oguro et autres

To develop novel inhibitor of apoptosis (IAP) proteins antagonists, we designed a bicyclic octahydropyrrolo[1,2-a]pyrazine scaffold as a novel proline bioisostere. This design was based on the X-ray co-crystal structure of four N-terminal amino acid residues (AVPI) of the second mitochondria-derived activator of …

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CCDC 888088: Experimental Crystal Structure Determination

Kentaro Hashimoto, Bunnai Saito, Naoki Miyamoto, Yuya Oguro et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

CCDC 713670: Experimental Crystal Structure Determination

H. Ishikawa, Denise A. Colby, S. Seto, Porino Va et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

Synthesis of Vinblastine

H. Ishikawa, Denise A. Colby, Shigeki Seto, Porino Va et autres

Significance A remarkably detailed mechanistic and labeling study was used to elucidate the mechanism of an iron(III)-promoted biomimetic synthesis of vinblastine. A key step is the inter­ception of the azabenzofulvene D by vindoline to generate the coupling product E with the correct …

Total Synthesis of Vinblastine, Vincristine, Related Natural Products, and Key Structural Analogues

Hayato Ishikawa, David A. Colby, Shigeki Seto, Porino Va et autres

Full details of the development of a direct coupling of catharanthine with vindoline to provide vinblastine are described along with key mechanistic and labeling studies. Following an Fe(III)-promoted coupling reaction initiated by generation of a presumed catharanthine radical cation that undergoes a …

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