A5056030117- Synthesis and biological activity
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and Reactions of Organic Compounds
- Synthesis of β-Lactam Compounds
- Synthesis and Biological Evaluation
- Synthesis of Tetrazole Derivatives
- Click Chemistry and Applications
- Phenothiazines and Benzothiazines Synthesis and Activities
- Antibiotic Resistance in Bacteria
- Chemical Synthesis and Analysis
- Mesenchymal stem cell research
- Fluorine in Organic Chemistry
- Antibiotics Pharmacokinetics and Efficacy
- HIV/AIDS drug development and treatment
- Synthesis and Reactivity of Sulfur-Containing Compounds
- HIV Research and Treatment
- Microbial Natural Products and Biosynthesis
- Organophosphorus compounds synthesis
- Sulfur-Based Synthesis Techniques
- Organic Chemistry Cycloaddition Reactions
- Carbohydrate Chemistry and Synthesis
- Phosphorus compounds and reactions
- Liver physiology and pathology
- Monoclonal and Polyclonal Antibodies Research
- Structural and Chemical Analysis of Organic and Inorganic Compounds
Nagoya University
2008-2019
Kariya Toyota General Hospital
2019
Nagoya University Hospital
2017
Takeda (Japan)
1994-2013
Kyushu University
2013
Shionogi (Japan)
1977-2008
Showa Pharmaceutical University
2006-2007
Nagoya City University
1998
Philadelphia University
1987
Engrafted mesenchymal stem cells from human deciduous dental pulp (SHEDs) support recovery neural insults via paracrine mechanisms that are poorly understood. Here we show the conditioned serum-free medium (CM) SHEDs, administered intrathecally into rat injured spinal cord during acute postinjury period, caused remarkable functional recovery. The ability of SHED-CM to induce was associated with an immunoregulatory activity induced anti-inflammatory M2-like macrophages. Secretome analysis...
Abstract Chronic liver injury from various causes often results in fibrosis (LF). Although the possesses endogenous tissue-repairing activities, these can be overcome by sustained inflammation and excessive fibrotic scar formation. Advanced LF leads to irreversible cirrhosis subsequent failure and/or hepatic cancer. Here, using mouse carbon tetrachloride (CCl4)-induced model, we showed that a single intravenous administration of stem cells derived human exfoliated deciduous teeth (SHEDs) or...
In acute liver failure (ALF), a poorly controlled innate immune response causes massive hepatic destruction, which elicits systemic inflammatory response, progressive multiple organ and ultimate sudden death. Although the has inherent tissue-repairing activities, its regeneration during ALF fails, orthotopic transplantation is only curative approach. Here we show that single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or SHED-derived...
Abstract Effective treatments for acute liver failure (ALF) are still lacking. We recently reported that a single intravenous administration of serum-free conditioned medium from stem cells derived human exfoliated deciduous teeth (SHED-CM) into the D-galactosamine (D-Gal)-induced rat ALF model improves injury. However, specific factors in SHED-CM responsible resolving remain unclear. Here we found depleting two anti-inflammatory M2 macrophage inducers—monocyte chemoattractant protein-1...
Syn-and anti-isomers of 7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-cephalosporins were synthesized selectively. These new cephalosporins exhibited excellent activities against a wide variety bacteria including those which are resistant to β-lactamase susceptible currently available. The syn-isomers showed higher than the anti-isomers.
(2R,3R)-2-(2,4-Difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl )-2-butano l [(2R,3R)-7] and its stereoisomers [(2S,3R)-, (2S,3S)- (2R,3S)-7] were prepared from the optically active oxiranes 6 by a newly developed ring-opening reaction evaluated for antifungal activity. The thiol (2R,3R)-7 showed extremely potent activity in vitro vivo. oxirane (2R,3S)-6, useful intermediate synthesis of sulfur-containing azoles 5, was synthesized methyl (R)-lactate [(R)-8] via eight steps...
A novel lead compound, N-{3-[4-(4-fluorobenzoyl)piperidin-1-yl]propyl}-1-methyl-5-oxo-N-phenylpyrrolidine-3-carboxamide (1), was identified as a CCR5 antagonist by high-throughput screening using [125I]RANTES and CCR5-expressing CHO cells. The IC50 value of 1 1.9 μM. In an effort to improve the binding affinity 1, series 5-oxopyrrolidine-3-carboxamides synthesized. Introduction 3,4-dichloro substituents central phenyl ring (10i, IC50=0.057 μM; 11b, IC50=0.050 μM) or replacing 1-methyl group...
1-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1: TAK-456) was selected as a candidate for clinical trials, but since its water-solubility insufficient an injectable formulation, the quaternary triazolium salts 2 were designed water-soluble prodrugs. Among prodrugs prepared,...
A new series of optically active antifungal azoles, N-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-tria zol-1- yl)propyl]-N'-(4-substituted phenyl)-3(2H,4H)-1,2,4-triazolones (1,2) and 5(1H,4H)-tetrazolones (3), were prepared from the triflate derivative (1S)-1-[(2R)-2-(2,4-difluorophenyl)-2-oxiranyl]ethanol (13) by an SN2 displacement reaction with anion azolone (17-19) subsequent ring-opening 1H-1,2,4-triazole. The oxiranylethanol 13 was synthesized methyl (R)-lactate in...
1-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone [(1R,2R)-1: TAK-456] is a new antifungal agent selected as candidate for clinical trials. The three stereoisomers [(1S,2R)-, (1S,2S)- and (1R,2S)-1] of this compound were prepared authentic samples to determine the enantiomeric diastereomeric purity TAK-456 well compare their in vitro activity. Pharmacokinetic studies using rats identified existence...
The synthesis of 6,7-cis-7-(1-hydroxy-1-methylethyl)-3-oxa-1-azabicyclo[4.2.0]octan-8-ones (3a, b), key intermediates for the preparation 5,6-cis-carbapenem antibiotic C-19393 H2{sodium (5R, 6R)-3-[(E)-(2-acetamidoethenyl)-(R)-sulphinyl]-6-(1-hydroxy-1-methylethyl)-7-oxo-1-azabicyclo-[3.2.0]hept-2-ene-2-carboxylate}(1a) and its derivatives, was investigated. Sulphenylation 3-oxa-1-azabicyclo[4.2.0]octan-8-ones (2a, followed by aldol reaction with acetone, gave...
In an effort to find potent antifungal agents, optically active sulfur-containing triazole derivatives, sulfides (3) and sulfonamides (4), were prepared evaluated for activity against Candida albicans in vitro vivo. The by the reaction of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl )-2-butanol (1) with various heteroarylmethyl chlorides presence sodium methoxide. (4) synthesized starting from disulfide (15) three steps including oxidation corresponding sulfenamides...
New routes for the synthesis of optically active antifungal triazoles 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1b) and 3-14-(1H-1,2,3-triazol-1-yl)phenyl]-2-imidazolidinone analog (1a) that possess an imidazolidine nucleus were established. The key synthetic intermediates, (2R,3R)-3-(2,2-diethoxvethyl)amino-2-(2,4-difluorophenyl)-1-(1H1,2,4-triazol-1-yl)-2-butanol (8)...
2-[(1R, 2R)-2-(2, 4-Difluorophenyl)-2-hydroxy-1-lmethyl-3-(1H-1, 2, 4-triazol-1-yl)propyl]-4-[4-(2, 3, 3-tetrafluoropropoxy)phenyl]-3(2H, 4H)-1, 4-triazolone [(1R, 2R)-1 : TAK-187] is a new antifungal agent selected as candidate for clinical trials. The three stereoisomers [(1S, 2S)-, (1R, 2S)- and (1S, 2R)-1] of this compound were prepared to clarify the relationship between stereochemistry biological activities. In vitro in vivo assays activity revealed that TAK-187 most potent among four...
A new type of 5, 6-cis-carbapenems (racemic) having a sulfonyl group in the C-6 side-chain were synthesized by employing synthetic methodology reported our previous papers, and an alternative stereocontrolled synthesis these was achieved starting from 8-oxo-7-azabicyclo [4.2.0] oct-3-ene (14) via intramolecular aldol condensation as key step. Chiral also (1S, 6R) -8-oxo-7-azabicyclo (29), which derived cis-1, 2, 6-tetrahydrophthalic anhydride. The carbapenems thus obtained proved to be...
(2R, 3R)-3-Azolyl-2-(substituted phenyl)-1-(1H-1, 2, 4-triazol-1-yl)-2-butanols (III) were prepared from 3S)-3-methyl-2-(substituted phenyl)-2-(1H-1, 4-triazol-1-yl)methyloxiranes (21a-f) by a ring-opening reaction with 1H-1, 3-triazole and 1H-tetrazole evaluated for antifungal activity against Candida albicans in vitro vivo. The optically active oxiranes (21a-f), which serve as the key synthetic intermediates, synthesized 1-[(2R)-2-(3, 4, 5,...