A5071398221- Asymmetric Synthesis and Catalysis
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Chemical synthesis and alkaloids
- Chemical Synthesis and Reactions
- Helicobacter pylori-related gastroenterology studies
- Gastric Cancer Management and Outcomes
- Axial and Atropisomeric Chirality Synthesis
- Cardiovascular Function and Risk Factors
- Cancer therapeutics and mechanisms
- Synthesis and Catalytic Reactions
- Synthetic Organic Chemistry Methods
- Crystallization and Solubility Studies
- Atrial Fibrillation Management and Outcomes
- X-ray Diffraction in Crystallography
- Advanced Synthetic Organic Chemistry
- Metastasis and carcinoma case studies
- Chemical Synthesis and Analysis
- Digestive system and related health
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Gastrointestinal Tumor Research and Treatment
- Cardiac Imaging and Diagnostics
- Cardiovascular Disease and Adiposity
Academia Sinica
2024
University of Alberta
2024
National Taiwan University
2024
Otsuka (Japan)
2009-2023
Tri-Institutional Therapeutics Discovery Institute
2016-2021
Takeda (Japan)
2010-2019
Gifu University
2011-2018
Osaka City University
2001-2015
Kindai University
2008-2015
Kindai University Sakai Hospital
2015
Background Tuberculosis (TB) is still a leading cause of death worldwide. Almost third the world's population infected with TB bacilli, and each year approximately 8 million people develop active 2 die as result. Today's treatment, which dates back to 1970s, long burdensome, requiring at least 6 mo multidrug chemotherapy. The situation further compounded by emergence multidrug-resistant (MDR-TB) infection's lethal synergy HIV/AIDS. Global health philanthropic organizations are now pleading...
In an effort to develop potent new antituberculosis agents that would be effective against both drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis, we prepared a novel series optically active 6-nitro-2,3-dihydroimidazo[2,1-b]oxazoles substituted at the 2-position with various phenoxymethyl groups methyl group investigated in vitro vivo activity these compounds. Several derivatives showed activity, compound 19 (OPC-67683) particular displayed excellent M. tuberculosis...
Abstract The catalytic enantioselective oxidation is an extremely important process in organic synthesis and numbers of effort to improve this have been reported so far. Although nitroso azo compounds are attractive tools for hydroxylation amination compounds, no reports on a asymmetric version these reactions had until recently. main issues were their high unique reactivities. In review, we would like introduce the recent advances area.
The aim of this prospective study was to evaluate left atrial (LA) function for the prediction increased risk new-onset non-valvular fibrillation (AF). Risk stratification AF based on LA remodelling may have a major public health impact. Although volume (LAV) or dimension been proposed as predictors AF, other predictive parameters not yet fully examined. emptying (EF), strain rate (SR), and LAV were evaluated in apical four-chamber view by speckle tracking echocardiography 580 consecutive...
Left atrial volume (LAV) has been proposed as a predictor of fibrillation (AF) and LA function investigated by velocity vector imaging (VVI) echocardiography. The aim this study was to determine whether associated with the existence AF.We examined emptying (EF) global strain rate (SR) regional during three phases cardiac cycle (reservoir, conduit, booster pump phase). parameters were measured (apical four-chamber view) VVI in 302 subjects [126 sinus rhythm, 91 paroxysmal AF (PAF), 85 chronic...
The only currently commercialized point-of-care assay for tuberculosis (TB) that measures lipoarabinomannan (LAM) in urine (Alere LF-LAM) has insufficient sensitivity. We evaluated the potential of 100 novel monoclonal antibody pairs targeting a variety LAM epitopes on sensitive electrochemiluminescence platform to improve diagnostic accuracy. In screening, many showed high reactivity purified but performed poorly at detecting urinary clinical samples, suggesting differences antigen...
Significance Protozoal proteasome is a validated target for antimalarial drug development, but species selectivity of reported inhibitors suboptimal. Here we identify with improved malaria β5 subunit over each active human proteasomes. These compounds kill the parasite in stage its life cycle. They interact synergistically β2 inhibitor and artemisinin. Resistance to arose through point mutation nonproteolytic β6 subunit. The same made mutant strain more sensitive less fit withstand...
Tuberculosis (TB) infection was responsible for an estimated 1.3 million deaths in 2017. Better diagnostic tools are urgently needed. We sought to determine whether accurate TB antigen detection blood or urine has the potential meet WHO target product profiles of active TB.We developed Electrochemiluminescence (ECL) immunoassays Lipoarabinomannan (LAM) and ESAT-6 with limits pg/ml range used them compare concentrations two antigens serum 81 HIV-negative -positive individuals presumptive...
Chiral 1,2-diols have been prepared from alpha-aminoxylated aldehydes or cyclohexanone and Grignard reagents with L-proline its tetrazole derivative as the catalyst. The presence of ate complex CeCl(3)2 LiCl is essential for high overall yields good selectivities (see scheme; DMSO = dimethyl sulfoxide, THF tetrahydrofuran, Tol tolyl).
ABSTRACT The increasing global burden of multidrug-resistant tuberculosis (MDR-TB) requires reliable drug susceptibility testing that accurately characterizes and resistance pathogenic bacteria to effectively treat patients with this deadly disease. Delamanid is an anti-TB agent first approved in the European Union 2014 for treatment pulmonary MDR-TB adults. Using agar proportion method, delamanid MIC was determined 460 isolates: 316 from enrolled a phase 2 clinical trial, 76 two early...
Background Lipoarabinomannan (LAM) is a major antigen of Mycobacterium tuberculosis (MTB). In this report, we evaluated the ability novel immunoassay to measure concentrations LAM in sputum as biomarker bacterial load prior and during treatment pulmonary (TB) patients. Methods findings Phage display technology was used isolate monoclonal antibodies binding epitopes unique from MTB slow-growing nontuberculous mycobacteria (NTM). Using these antibodies, sandwich enzyme-linked immunosorbent...
This communication describes studies in which an azo hetero-Diels−Alder adduct was furnished high regio- and enantioselectivity using azopyridine as a reagent silver catalyst. The obtained easily converted to the corresponding chiral 1,4-diamino alcohol.
New nucleophiles for the O-nitroso aldol reaction in form of readily prepared disilanyl enol ethers make this transformation more practical and versatile. A silver catalyst with a chiral biaryl phosphite ligand promotes title high enantio- regioselectivity (see scheme). R1,R2 = H, Ar; TMS trimethylsilyl.
We have previously shown that a recombinant baculovirus displays Plasmodium berghei circumsporozoite protein (PbCSP), homolog of the leading human malaria vaccine candidate, on viral envelope protected 60% mice against P. infection. Here, we describe second-generation based "baculovirus dual expression system," which drives PbCSP by promoter consists tandemly arranged baculovirus-derived polyhedrin and mammal-derived cytomegalovirus promoters. The baculovirus-based not only displayed but...
Phosphodiesterase (PDE) 2A inhibitors have emerged as a novel mechanism with potential therapeutic option to ameliorate cognitive dysfunction in schizophrenia or Alzheimer's disease through upregulation of cyclic nucleotides the brain and thereby achieve potentiation nucleotide signaling pathways. This article details expedited optimization our recently disclosed pyrazolo[1,5-a]pyrimidine lead compound 4b, leading discovery clinical candidate 36 (TAK-915), which demonstrates an appropriate...
To develop novel inhibitor of apoptosis (IAP) proteins antagonists, we designed a bicyclic octahydropyrrolo[1,2-a]pyrazine scaffold as proline bioisostere. This design was based on the X-ray co-crystal structure four N-terminal amino acid residues (AVPI) second mitochondria-derived activator caspase (Smac) with X-chromosome-linked IAP (XIAP) protein. Lead optimization this to improve oral absorption yielded compound 45, which showed potent cellular IAP1 (cIAP1 IC(50): 1.3 nM) and XIAP...
Total synthesis of the potent AMPA/KA receptor antagonist (−)-kaitocephalin (1) and its three diastereomers has been accomplished. The features strictly substrate-controlled operations to α-formylglutamate 3 starting with α-hydroxymethylglutamate 4. requisite 2R,3S,7R-stereocenters were efficiently constructed by manipulation stereoselective reactions: dihydroxylation 7 followed azide substitution corresponding thionocarbonate 10 Cu-mediated allylation an acyliminium ion 21. All protecting...
Four possible stereoisomers of manzacidin B were synthesized using stereochemically defined synthetic routes via the azide 7 and oxazoline 11 starting with (R)-α-methyl Garner aldehyde 5. Comparisons spectroscopic data isomers 4a−d those natural revised proposed structure 3 to (4S,5S,6R)-4d.