A5007744856- Chemical Synthesis and Analysis
- Asymmetric Synthesis and Catalysis
- Synthetic Organic Chemistry Methods
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Carbohydrate Chemistry and Synthesis
- Chemical synthesis and alkaloids
- Oxidative Organic Chemistry Reactions
- Synthesis and Catalytic Reactions
- Chemical Synthesis and Reactions
- Ion Channels and Receptors
- Fluorine in Organic Chemistry
- Sexual function and dysfunction studies
- Enzyme Catalysis and Immobilization
- Organic Chemistry Cycloaddition Reactions
- Asthma and respiratory diseases
- Synthesis and Reactions of Organic Compounds
- Mass Spectrometry Techniques and Applications
- Phosphodiesterase function and regulation
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Alkaloids: synthesis and pharmacology
- Click Chemistry and Applications
- Phosphorus compounds and reactions
- Organophosphorus compounds synthesis
- Cyclopropane Reaction Mechanisms
Institute of Cancer Research
2022
Novartis (United Kingdom)
2001-2014
Novartis (Switzerland)
2000-2011
Novartis (United States)
2009
University of Oxford
1996-2008
University of Southampton
2003-2004
GlaxoSmithKline (United Kingdom)
2004
Novartis (Spain)
2003
Universitat de Barcelona
2003
GTx (United States)
2000
Inhibition of airway epithelial sodium channel (ENaC) function enhances mucociliary clearance (MCC). ENaC is positively regulated by channel-activating proteases (CAPs), and CAP inhibitors are therefore predicted to be beneficial in diseases associated with impaired MCC. The aims the present study were 1) identify low-molecular-weight CAPs 2) establish whether such would translate into a negative regulation vivo, consequent enhancement To this end, camostat, trypsin-like protease inhibitor,...
[reaction: see text] Catalytic Sc(OTf)(3) greatly increases the efficiency of hydrogen peroxide mediated monooxidation alkyl-aryl sulfides and methyl cysteine containing peptides. The method is high yielding, compatible with many widely used protecting groups, suitable for solid-phase applications proceeds minimum over-oxidation.
A general strategy for the production of pyrrolizidine alkaloids is described, starting from intermediate (+)−9. The key features are diastereoselective dihydroxylation, inversion at ring junction by hydroboration an enamine, and closure to form bicyclo system. This route attractive because its brevity versatility; four natural products were prepared with differing stereochemistry substitution patterns. Finally, this work allowed assignment absolute 2,3,7-triepiaustraline hyacinthacine A7.
Prokineticin 2 (PROK2) is an inflammatory cytokine-like molecule expressed predominantly by macrophages and neutrophils infiltrating sites of tissue damage. Given the established role prokineticin signaling on gastrointestinal function, we have explored Prok2 gene expression in conditions tract assessed possible consequences gut physiology.Prokineticin was examined normal colitic tissues using qPCR immunohistochemistry. Functional responses to PROK2 were studied calcium imaging a novel...
Bridgehead metallation is possible in a ketone having the welwistatin skeleton, and this facilitates installation of isothiocyanate function present natural product, also enables synthesis remarkable bridgehead alkenes.
The enzymatic desymmetrization of 2,2- and 2,5-disubstituted pyrroline compounds is reported in a procedure which gives access to both enantiomers excellent enantiomeric excess good yield. enzyme reaction precursors are formed easily from two readily available substituted pyrroles using ammonia (Na/NH3) ammonia-free (Li/DBB) Birch reduction conditions.
The partial reduction of 2,5-pyrrole diester 1 followed by enantioselective protonation in situ to furnish synthetically useful building blocks is described. An enantiomeric excess up 74% was achieved using (−)-ephedrine and related analogues as chiral proton sources. pyrroline product obtained could be recrystallized give enantiomerically pure material.
1,3-Dipolar cycloaddition of nitrile oxides, formed in situ by dehydration primary nitro compounds, with pyrrolidine enamines protected γ- or δ-amino-β-keto esters affords isoxazole-4-carboxylates; these undergo lactam formation and N–O bond cleavage to afford 3-acyltetramic acids 3-acyl-4-hydroxypyridin-2-ones.
Caco-2 screens are routinely used in laboratories to measure the permeability of compounds and can identify substrates efflux transporters. In this study, we hypothesized that transporter inhibition a compound be predicted by an intracellular metabolic signature cells assay test intestinal permeability. Using selective inhibitors knock-out (KO) targeted Liquid Chromatography tandem Mass Spectrometry (LC-MS) method, identified 11 metabolites increased with depleted P-glycoprotein (Pgp)...
Dyad beads, bearing both a substrate and catalyst, were prepared to enable direct split mix bead based screening for catalysis.
1, 3-Dipolar cycloaddition of nitrite oxides to enamines formed from protected γ-amino- or γ-hydroxy-β-keto esters affords isoxazolecarboxylic that can be converted into 3-acyltetramic acids via dihydropyrroloisoxazol-4-ones, 3-acyltetronic acids.
The canonical transient receptor potential channel subfamily (TRPC3, TRPC6, and TRPC7) contains Ca(2+) permeable non-selective cation channels that are widely expressed in a variety of tissues. There is increasing evidence implicating TRPC channels, particularly TRPC3 6, physiological pathophysiological processes, eliciting interest these as novel drug targets. Electrophysiology remains benchmark technique for measuring ion function accurately determining the pharmacological effects...
A series of novel 2-oxo esters with protected alcohols at the 3-, 4-, 5-, 6- and 7-positions has been prepared either via coupling an aldehyde organometallic reagent (Zn, In or Cr) a one-carbon homologation precursor acid. one-pot dual enzyme system was used to convert simpler acids (with single MOM ether C-3 C-4) into enantiopure 2,3- 2,4-dihydroxy in good yields, but cases more complex trisubstituted substrates, significant decomposition occurred. Biotransformations have proved valuable...
Ion-extraction mass spectrometry of ladders mixtures isotopically labeled compounds from single beads allows the unambiguous sequencing bead-based peptides and offers significant advantages over traditional methods library analysis.