A5011864637- X-ray Diffraction in Crystallography
- Receptor Mechanisms and Signaling
- Crystallization and Solubility Studies
- Cytokine Signaling Pathways and Interactions
- Organoselenium and organotellurium chemistry
- Estrogen and related hormone effects
- Radical Photochemical Reactions
- Sulfur-Based Synthesis Techniques
- Bioactive Compounds and Antitumor Agents
- Urinary Bladder and Prostate Research
- Silicon Nanostructures and Photoluminescence
- Traditional and Medicinal Uses of Annonaceae
- Silicon and Solar Cell Technologies
- Advanced Computing and Algorithms
- Photopolymerization techniques and applications
- Synthesis and Biological Evaluation
- Synthesis and biological activity
- Alkaloids: synthesis and pharmacology
- Psoriasis: Treatment and Pathogenesis
- Chemical synthesis and alkaloids
- Hormonal Regulation and Hypertension
- Microbial Natural Products and Biosynthesis
- Pharmacological Receptor Mechanisms and Effects
- Cardiac electrophysiology and arrhythmias
- Pharmacological Effects of Natural Compounds
Takeda (Japan)
2016-2019
Chiba Institute of Technology
2018
The University of Tokyo
2003-2011
Osaka City University
2005
Tokyo University of Science
1999
Retinoic acid receptor-related orphan receptor γt (RORγt) agonists are expected to provide a novel class of immune-activating anticancer drugs via activation Th17 cells and Tc17 cells. Herein, we describe structure-based functionality switching approach from in house well-optimized RORγt inverse potent agonists. We succeeded the identification agonist 5 without major chemical structure change. The biochemical response was validated by molecular dynamics simulation studies that showed helix...
Abstract Stereocontrolled total synthesis of (+)-vinblastine ( 1 ) has been achieved using a novel radical-mediated indole developed in our laboratories. The isothiocyanate 18 , prepared readily from quinoline 17 underwent facile addition the malonate anion to give 19 . o -alkenylthioanilide was then converted 20 by radical cyclization and protection. (−)-Vindoline 2 this key intermediate highly efficient manner. core 11-membered 3 constructed similarly quinoline. critical coupling reaction...
A novel structural class of iminopyridine derivative 1 was identified as a potent and selective human α1D adrenoceptor (α1D adrenergic receptor; α1D-AR) antagonist against α1A- α1B-AR through screening an in-house compound library. From initial structure-activity relationship studies, we found lead 9m with hERG K(+) channel liability. To develop analogues reduced inhibition, combination site-directed mutagenesis docking studies employed. Further optimization led to the discovery (R)-9s 9u,...
Retinoic-acid-related orphan receptor γt (RORγt) inverse agonists could be used for the treatment of autoimmune diseases. Previously, we reported a novel quinazolinedione 1 with flexible linear linker as RORγt agonist. A U-shaped conformation in complex structure protein was confirmed. Further improvement pharmacokinetic (PK) profiles required because low drug exposure mice upon oral administration (mouse AUC a: 27 ng ⋅ h mL-1 at mg kg-1 , p.o.). To improve PK profiles, conformationally...
A new method for the synthesis of 2,3-dialkylindoles is described. The silyltelluride-mediated coupling reaction imines and 2-alkenylphenylisocyanides selectively occurred at isocyanide moiety to give corresponding imidoyltelluride. Tin hydride-mediated intramolecular cyclization imidoyltelluride affords in good excellent combined yields.