A5016475063- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Visual perception and processing mechanisms
- Crystallography and molecular interactions
- Synthetic Organic Chemistry Methods
- Asymmetric Synthesis and Catalysis
- Synthesis of Indole Derivatives
- Liver Disease Diagnosis and Treatment
- Hepatitis B Virus Studies
- Cancer Treatment and Pharmacology
- Radical Photochemical Reactions
- Polyamine Metabolism and Applications
- S100 Proteins and Annexins
- Eicosanoids and Hypertension Pharmacology
- Inflammatory mediators and NSAID effects
- Tactile and Sensory Interactions
- Cell Adhesion Molecules Research
- Protein Kinase Regulation and GTPase Signaling
- Asymmetric Hydrogenation and Catalysis
- Hepatitis C virus research
- Flow Measurement and Analysis
- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- Catalytic C–H Functionalization Methods
- Liver Diseases and Immunity
Yamagata University
2023-2024
Okayama University Hospital
2017-2023
Yokohama National University
2008-2023
Takeda (Japan)
2012-2022
Fukuyama University
2021
Pharmac
2021
University of Hong Kong
2020
Westlake University
2020
University of Edinburgh
2020
Universidade de Santiago de Compostela
2020
The first general catalytic enantioselective conjugate addition of cyanide to β,β-disubstituted α,β-unsaturated ketones and N-acylpyrroles was developed using a strontium catalyst derived from Sr(OiPr)2 new chiral ligand 5. reaction exhibited excellent enantioselectivity wide substrate scope 0.5−10 mol % catalyst. 1,4-Adducts containing β-quaternary carbons were exclusively produced over 1,2-adducts. ESI-MS analysis the indicated that active trimetallic Sr/5 = 3:5 complex. exclusive...
Mcl-1 and Bcl-xL are crucial regulators of apoptosis, therefore dual inhibitors both proteins could serve as promising new anticancer drugs. To design Mcl-1/Bcl-xL inhibitors, we performed structure-guided analyses the corresponding selective inhibitors. A cocrystal structure a pyrazolo[1,5-a]pyridine derivative with protein was successfully determined revealed protein–ligand binding mode. The key for inhibition further confirmed through substructural analysis ABT-263, representative...
The first synthetically useful catalytic enantioselective conjugate addition of cyanide to enones is described. optimized conditions involved a Gd catalyst (5 or 10 mol %) derived from ligands 3 4 and 1:1 ratio TBSCN 2,6-dimethylphenol. reaction exhibited excellent high enantioselectivity wide substrate scope. Moreover, the 1,4-adduct was exclusively produced over 1,2-adduct. complete regioselectivity due both stabilization 1,4-selective silylated polymetallic (7) using TBS group ability...
A formal synthesis of the antitumor diterpenoid paclitaxel (Taxol) is described. The ABC ring paclitaxel, synthesized starting from 1,3-cyclohexanedione and tri-O-acetyl-d-glucal by SmI2-mediated cyclization as key transformation, was successfully converted to Takahashi's tetracyclic oxetane intermediate. double Chugaev reaction employed for introduction strained bridgehead olefin, stereoselective formation afforded known synthetic intermediate, completing paclitaxel.
A convergent synthesis of the ABC ring antitumor natural product paclitaxel (Taxol) is described. SmI2-mediated reductive cyclization an allylic benzoate possessing aldehyde function, synthesized from tri-O-acetyl-d-glucal and 1,3-cyclohexanedione, smoothly afforded highly strained 6–8–6 tricarbocyclic structure in 66% yield.
Cytoplasmic dyneins are motor proteins in the AAA+ superfamily that transport cellular cargos toward microtubule minus-ends. Recently, ciliobrevins were reported as selective cell-permeable inhibitors of cytoplasmic dyneins. As is often true for first-in-class inhibitors, use has part been limited by low potency. Moreover, suboptimal chemical properties, such potential to isomerize, have hindered efforts improve ciliobrevins. Here, we characterized structure and designed conformationally...
The integrin αVβ3 receptor has been implicated in several important diseases, but no antagonists are approved for human therapy. One possible limitation of current small-molecule is their ability to induce a major conformational change the that induces it adopt high-affinity ligand-binding state. In response, we used structural inferences from pure peptide antagonist design TDI-4161 and TDI-3761. Both compounds inhibit αVβ3-mediated cell adhesion ligands, do not as judged by antibody...
Deoxyhypusine synthase (DHPS) utilizes spermidine and NAD as cofactors to incorporate a hypusine modification into the eukaryotic translation initiation factor 5A (eIF5A). Hypusine is essential for eIF5A activation, which, in turn, plays key role regulating protein of selected mRNA that are associated with synthesis oncoproteins, thereby enhancing tumor cell proliferation. Therefore, inhibition DHPS promising therapeutic option treatment cancer. To discover novel lead compounds target DHPS,...
Prenatal tests of hearing are practically great value in making an early diagnosis deafness. Attempts were made to develop a relatively simple method prenatal hearing, and 134 fetuses the 6th–10th month period pregnancy examined by means this method. Pure tones frequency 500, 1,000 2,000 Hz generated conventional audiometer used as acoustic stimuli. Movements fetus well changes fetal pulse rate occurring during or immediately after stimulation criteria for auditory response. One hundred...
Abstract Although an association has been reported between diuretics and myocarditis, it is unclear whether the risk of immune checkpoint inhibitor (ICI)‐induced myocarditis affected by concomitant diuretics. Thus, aim this work was to evaluate impact on ICI‐induced myocarditis. This cross‐sectional study used disproportionality analysis a pharmacovigilance database assess with various in patients receiving ICIs via data entered into VigiBase through December 2022. Multiple logistic...
Natural deep eutectic solvents (NADESs), which consist of natural components, have attracted attention as environmentally friendly solvents. We describe the design and synthesis monomers (NADEMs) NADEM-based polymers.
Gaucher disease (GD), the most common lysosomal storage disorders, is caused by GBA gene mutations resulting in glycosphingolipids accumulations various tissues, such as brain. While suppressing glycosphingolipid accumulation central strategy for treating peripheral symptoms of GD, there no effective treatment nervous system symptoms. As biosynthesis starts from ceramide glycosylation glucosylceramide synthase (GCS), inhibiting GCS brain a promising neurological GD. Herein, we discovered...
Inhibition of glucosylceramide synthase (GCS) is a major therapeutic strategy for Gaucher's disease and has been suggested as potential target treating Parkinson's disease. Herein, we report the discovery novel brain-penetrant GCS inhibitors. Assessment structure-activity relationship revealed unique pharmacophore in this series. The lipophilic ortho-substituent aromatic ring A appropriate directionality B were key potency. Optimization absorption, distribution, metabolism, elimination,...
Moderately oxidizing thioxanthylium photoredox catalysts that operate under irradiation with green light have been developed. These exhibit relatively moderate excited-state reduction potentials [E1/2(C*/C•-) = 1.75-1.94 V vs saturated calomel electrode (SCE)] and can efficiently promote radical-cation Diels-Alder reactions light. Interestingly, β-halogenostyrenes (Ep/2 1.57-1.61 SCE) are well tolerated, affording synthetically useful halocyclohexenes.
We report the one-pot synthesis of 2,2-disubstituted chromanes with electron-withdrawing substituents. This reaction provides a simple yet efficient route to wide range electron-deficient in high yield and excellent regioselectivity. The salicylaldehyde 1,1-disubstituted ethylenes smoothly furnishes these chromanes, which can be further transformed into functionalized or chromene. For example, BW683C was effectively synthesized from 5-chlorosalicylaldehyde 4-chlorostyrene two steps yield....
Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) is generated by phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) from (PI4P). Structurally diverse and selective inhibitors against PIP5Ks are required to further elucidate the therapeutic potential for PIP5K inhibition, although effects of inhibition on various diseases their symptoms, such as cancer chronic pain, have been reported. Our medicinal chemistry efforts led novel potent PIP5K1C inhibitors. Compounds 30 33 not only showed...
It is therapeutically important to elucidate the factors involved in radiation resistance of tumors. We previously showed that ATP released from mouse melanoma B16 cells response γ-irradiation, but role adenosine, a metabolite ATP, still unclear. Here, we show adenosine A2B receptor DNA damage repair and radioresistance cells. The after γ-irradiation was attenuated by pretreatment with antagonists, such as PSB603, while it enhanced agonists, BAY60-6583. γ-Irradiation decreased cell survival...
The creep damage process of high-Cr steel welded joints is characterized by the formation and growth voids prior to initiation cracking, this accounts for a large proportion life. Therefore, there has been much investigation into detection quantitative evaluation microcracks in use remaining life assessment. However, microstructure around still not well known. In study, test on joint Mod.9Cr-1Mo was conducted under 60 MPa at 650 °C. observation heat-affected zone (HAZ) made specimen...