A5000261087- Plant Parasitism and Resistance
- Fluorine in Organic Chemistry
- Plant and animal studies
- Allelopathy and phytotoxic interactions
- Cancer-related gene regulation
- Synthesis and Reactions of Organic Compounds
- Cellular transport and secretion
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Asymmetric Synthesis and Catalysis
- Cyclopropane Reaction Mechanisms
- Synthesis and Biological Evaluation
- Carbohydrate Chemistry and Synthesis
- Protein Kinase Regulation and GTPase Signaling
- Chemical synthesis and alkaloids
- HIV/AIDS drug development and treatment
- Toxin Mechanisms and Immunotoxins
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Acute Myeloid Leukemia Research
- Plant Virus Research Studies
- Oxidative Organic Chemistry Reactions
- Porphyrin and Phthalocyanine Chemistry
- Respiratory viral infections research
- NF-κB Signaling Pathways
Janssen (Belgium)
2011-2025
Vanderbilt University
1999-2021
Janssen (United States)
2021
Texas A&M University
2021
Université Paris Cité
2021
Centre National de la Recherche Scientifique
2021
Ningbo University
2021
Wenzhou University
2021
Lanzhou Institute of Chemical Physics
2021
Bristol-Myers Squibb (United States)
2009-2014
The development of HIV integrase (IN) strand transfer inhibitors (INSTIs) and our understanding viral resistance to these molecules have been hampered by a paucity available structural data. We recently reported cocrystal structures the prototype foamy virus (PFV) intasome with raltegravir elvitegravir, establishing general INSTI binding mode. now present an expanded set containing PFV intasomes complexed first- second-generation INSTIs at resolutions up 2.5 Å. Importantly, improved...
Various cardio‐active stimuli, including endothelin‐1 (ET‐1), exhibit potent arrhythmogenicity, but the underlying cellular mechanisms of their actions are largely unclear. We used isolated rat atrial myocytes and related changes in subcellular Ca 2+ signalling to ability various stimuli induce diastolic, premature extra transients (ECTs). For this, we recorded global spatially resolved signals indo‐1‐ fluo‐4‐loaded during electrical pacing. ET‐1 exhibited a higher arrhythmogenicity...
Elementary Ca2+ signals, such as ‘Ca2+ puffs’, which arise from the activation of inositol 1,4,5-trisphosphate receptors, are building blocks for local and global signalling. We characterized puffs in six cell types that expressed differing ratios three receptor isoforms. The amplitudes, spatial spreads kinetics events were similar each types. resemblance these suggests they a generic elementary signal and, furthermore, different isoforms functionally redundant at level subcellular Hormonal...
FENS-1 and DFCP1 are recently discovered proteins containing one or two FYVE-domains respectively. We show that the FYVE domains in these can bind PtdIns3P vitro with high specificity over other phosphoinositides. Exogenously expressed localises to early endosomes: this localisation requires an intact domain is sensitive wortmannin inhibition. The isolated of also endosomes. These results consistent current models FYVE-domain function cellular compartment. By contrast, exogenously displays a...
The α<sub>7</sub> nicotinic acetylcholine receptor (nAChR) is a potential therapeutic target for the treatment of cognitive deficits associated with schizophrenia, Alzheimer9s disease, Parkinson9s and attention-deficit/hyperactivity disorder. Activation nAChRs improved sensory gating function in animal models early clinical trials. Here we describe novel highly selective nAChR positive allosteric modulator, 2-[[4-fluoro-3-(trifluoromethyl)phenyl]amino]-4-(4-pyridinyl)-5-thiazolemethanol...
The discovery of BMS-605339 (35), a tripeptidic inhibitor the NS3/4A enzyme, is described. This compound incorporates cyclopropylacylsulfonamide moiety that was designed to improve potency carboxylic acid prototypes through introduction favorable nonbonding interactions within S1′ site protease. identification 35 enabled optimization and balance critical properties including pharmacokinetics (PK). achieved modulation P2* subsite which identified isoquinoline ring system as key template for...
The newly designed strigol analogue Nijmegen 1 (rac 7) was prepared in high overall yield starting from N-phthaloylglycine. This relatively simple exhibits bioactivity the stimulation of germination seeds parasitic weeds Striga hermonthica and Orobanche crenata. resolved its enantiomers 7 ent by using homochiral latent D-rings 11 12. show significant differences activity. Keywords: Striga; Orobanche; germination;
The naturally occurring sesquiterpene sorgolactone (2) belongs to the class of "strigolactones", which are highly potent germination stimulants for seeds parasitic weeds Striga and Orobanche. aim present work was synthesize all eight stereoisomers evaluate their activities in stimulation S. hermontica O. crenata. Two racemic diastereomers ABC part sorgolactone, rac.10a rac.10b respectively, were prepared coupled with homochiral latent D-ring synthons 12 ent.12. In this manner, four mixtures...
Abstract The protein arginine methyltransferase 5 (PRMT5) methylates a variety of proteins involved in splicing, multiple signal transduction pathways, epigenetic control gene expression, and mechanisms leading to expression required for cellular proliferation. Dysregulation PRMT5 is associated with clinical features several cancers, including lymphomas, lung cancer, breast cancer. Here, we describe the characterization JNJ-64619178, novel, selective, potent inhibitor, currently trials...
The synthesis of the complete family phosphatidylinositol phosphate analogues (PIPs) from five key core intermediates A-E is described. These compounds were obtained myo-inositol orthoformate 1 via regioselective DIBAL-H and trimethylaluminium-mediated cleavages a resolution-protection process using camphor acetals 10. Coupling cores with phosphoramidites 34 38, derived requisite protected lipid side chains, afforded fully-protected PIPs. Removal remaining protecting groups was achieved...
Fluorinated pyrazoles bearing additional functional groups that allow further functionalization are of considerable interest as building blocks in medicinal chemistry. The developed synthetic strategy for new 3-amino-4-fluoropyrazoles consists a monofluorination β-methylthio-β-enaminoketones using 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) toward the corresponding monofluorinated enaminoketones, followed by condensation with different hydrazines.
Abstract Colorectal cancer (CRC) is one of the most common causes cancer-related deaths in world and loss Adenomatous Polyposis Coli (APC) gene represents disease-initiating event majority CRC cases. Strategies for targeting APC-loss function (APC-LOF) may provide an opportunity to intercept tumorigenesis high-risk patients, such as those with Familial (FAP). To discover targets therapeutic intervention APC-LOF-driven disease, we conducted a high-throughput screen isogenic APC knockout...
All four optically pure stereoisomers of the strigol analogue GR24 were prepared via two different routes. In first approach enantiopure ABC-fragments 4 used as chiral source, whereas in alternative route both antipodes latent D-ring 6 employed. Bioassays revealed significant differences activity between stimulation germination parasitic weeds Striga hermonthica and Orobanche crenata. Keywords: Striga; Orobanche; germination,
Difluoropiperidines attract considerable interest from organic and medicinal chemists, but their synthesis is often problematic. This paper describes a new synthetic pathway toward valuable 3,3-difluoropiperidines starting suitable δ-chloro-α,α-difluoroimines. The latter imines can be synthesized via electrophilic fluorination of the corresponding δ-chloroimines using NFSI (N-fluorodibenzenesulfonimide) in acetonitrile. After hydride reduction imino bond subsequent intramolecular...