A5042573856- Synthetic Organic Chemistry Methods
- Asymmetric Synthesis and Catalysis
- Synthesis and Catalytic Reactions
- Carbohydrate Chemistry and Synthesis
- Quinazolinone synthesis and applications
- Cancer Treatment and Pharmacology
- Pancreatic and Hepatic Oncology Research
- Chemical Synthesis and Analysis
- Hormonal Regulation and Hypertension
- Aldose Reductase and Taurine
- Catalytic Cross-Coupling Reactions
- Synthesis of β-Lactam Compounds
- Organoboron and organosilicon chemistry
- Chemical synthesis and alkaloids
- Advanced Breast Cancer Therapies
- Molecular spectroscopy and chirality
- Advanced Synthetic Organic Chemistry
- Asymmetric Hydrogenation and Catalysis
- Glycosylation and Glycoproteins Research
- Cancer Cells and Metastasis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Peptidase Inhibition and Analysis
- Enzyme function and inhibition
- Estrogen and related hormone effects
- Hepatitis C virus research
London Centre for Nanotechnology
2023
Molecular Discovery (United Kingdom)
2017
Cancer Research UK
2016
Cancer Research Horizons
2007-2013
Discovery Laboratories (United States)
2010
Queen Mary University of London
2008
University College London
2007
Roche (United Kingdom)
1993-2002
University of York
1998-2002
University of Hertfordshire
2002
Abstract Protein kinase D (PKD) family members are increasingly implicated in multiple normal and abnormal biological functions, including signaling pathways that promote mitogenesis pancreatic cancer. However, nothing is known about the effects of targeting PKD Our inhibitor discovery program identified CRT0066101 as a specific all isoforms. The aim our study was to determine Initially, we showed autophosphorylated PKD1 PKD2 (activated PKD1/2) significantly upregulated cancer PKD1/2...
The Garner aldehyde-derived methylene alkene 5 and the corresponding benzyloxycarbonyl compound 25 undergo hydroboration with 9-BBN-H followed by palladium-catalyzed Suzuki coupling reactions aryl vinyl halides. After one-pot hydrolysis-oxidation, a range of known novel nonproteinogenic amino acids were isolated as their N-protected derivatives. These organoborane homoalanine anion equivalents are generated transformed under mild conditions wide functional group tolerance: electron-rich...
The lantibiotics are a class of highly posttranslationally modified small peptide antibiotics containing numerous lanthionine and dehydroamino acid residues. We have prepared peptides multiple acids cysteine residues in order to probe the biomimetic synthesis from their precursor peptides. A novel synthetic methodology was developed allow Cyclisations were rapid, quantitative regiospecific. Remarkably sequences alone appear contain sufficient information direct series stereo- regiospecific...
Structure-based design was applied to the optimization of a series 2-(quinazolin-2-yl)phenols generate potent and selective ATP-competitive inhibitors DNA damage response signaling enzyme checkpoint kinase 2 (CHK2). Structure-activity relationships for multiple substituent positions were optimized separately in combination leading 2-(quinazolin-2-yl)phenol 46 (IC(50) 3 nM) with good selectivity CHK2 against CHK1 wider panel kinases promising vitro ADMET properties. Off-target activity at...
VEGF (vascular endothelial growth factor) plays an essential role in angiogenesis during development and disease largely mediated by signalling events initiated binding of to its receptor, VEGFR2 (VEGF receptor 2)/KDR (kinase insert domain receptor). Recent studies indicate that activates PKD (protein kinase D) cells regulate a variety cellular functions, including events, proliferation, migration angiogenesis. To better understand the VEGF-mediated function, we characterized effects novel...
Glioblastoma multiforme (GBM) is the most common malignant brain tumor, which, despite combined modality treatment, reoccurs and invariably fatal for affected patients. Recently, a member of serine/threonine protein kinase D (PRKD) family, PRKD2, was shown to be potent mediator glioblastoma growth. Here we studied role PRKD2 in U87MG cell migration invasion response sphingosine-1-phosphate (S1P), an activator GBM mitogen. Time-lapse microscopy demonstrated that random significantly...
A high-throughput screen identified 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acid as a novel, highly potent (low nM), and isoform-selective (1500-fold) inhibitor of aldo-keto reductase AKR1C3: target interest in both breast prostate cancer. Crystal structure studies showed that the carboxylate group occupies oxyanion hole enzyme, while sulfonamide provides correct twist to allow dihydroisoquinoline bind an adjacent hydrophobic pocket. SAR around this lead positioning was critical,...
Two novel routes to C-linked glycosyl amino acids are described; the first involves elaboration of an exo-glycal and subsequent Ramberg–Bäcklund rearrangement a sulfone intermediate give, after functional group manipulation, protected C-glycosyl serine, while second uses hydroboration–Suzuki coupling same produce ultimately corresponding asparagine analogue.
The homochiral cyclic sulfinamide S(s)R-(+)-1 has been employed for the asymmetric synthesis of α-substituted benzylamines via benzylidene sulfinamides R(s)R-(–)-4. Following diastereoselective reduction and hydrolysis can be recycled in one step from sulfinic acid 11. addition zinc(II) bromide reverses diastereoselectivity diisobutylaluminium hydride (DIBAL) substrates 4. same reversal is not observed reactions analogues lacking an amide side chain. In case required exists form enamine 15,...
ABSTRACT Picornavirus replication is known to cause extensive remodeling of Golgi and endoplasmic reticulum membranes, a number the host proteins involved in viral complex have been identified, including oxysterol binding protein (OSBP) phosphatidylinositol 4-kinase III beta (PI4KB). Since both OSBP PI4KB are substrates for kinase D (PKD) PKD be control membrane vesicular lipid transport, we hypothesized that played role replication. We present multiple lines evidence support this...
Hepatitis C virus (HCV) is the cause of majority transfusion-associated hepatitis and a significant proportion community-acquired worldwide. Infection by HCV frequently leads to persistent infections that result in range clinical conditions including an asymptomatic carrier state, severe chronic active hepatitis, cirrhosis and, some cases, hepatocellular carcinoma. The genome consists single-stranded, positive sense RNA containing open reading frame approximately 9060 nucleotides. This...
Zirconium- and titanium-mediated diene metallabicyclisation–elimination–functionalisation have been compared, contrasted utilised for the preparation of 3,4-disubstituted 2,3,4-trisubstituted pyrrolidines in high yield excellent stereoselectivity. The zirconium-mediated methodology has employed as key step a partial synthesis (−)-α-kainic acid starting from D-serine, but metallabicyclisation sequence proceeded with poor stereocontrol. By contrast, total L-serine was accomplished using...
Titanium-mediated diene metallabicyclisation–elimination–functionalisation has been utilised for the preparation of syn-3,4-disubstituted and syn,syn-2,3,4-trisubstituted pyrrolidines in high yield excellent stereoselectivity; this methodology employed a total synthesis (–)-α-kainic acid starting from L-serine.