ORCID Profile
0000-0001-5588-1077
Current Organisation
University of Nottingham
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: American Chemical Society (ACS)
Date: 16-12-2015
DOI: 10.1021/ACS.JMEDCHEM.5B01664
Abstract: Fluorescently labeled ligands are useful pharmacological research tools for studying receptor localization, trafficking, and signaling processes via fluorescence imaging. They are also employed in fluorescent binding assays. This study is centered on the design, synthesis, and pharmacological evaluation of fluorescent probes for the opioid receptors, for which relatively few non-peptidic fluorescent probes currently exist. The known μ-opioid receptor (MOR) partial agonist, buprenorphine, was structurally elaborated to include an amidoalkylamine linker moiety that was coupled with a range of fluorophores to afford new fluorescent probes. All compounds proved to be selective MOR antagonists. Confocal fluorescence microscopy studies revealed that the probe incorporating a sulfonated cyanine-5 fluorophore was the most appropriate for imaging studies. This ligand was subsequently employed in an automated fluorescence-based competition binding assay, allowing the pKi values of several well-known opioid ligands to be determined. Thus, this new probe will prove useful in future studies of MOR receptor pharmacology.
Publisher: Wiley
Date: 23-05-2023
Abstract: Diazomethane is a powerful reagent for numerous chemical reactions such as esterifications and the homologation of carboxylic acids. Unfortunately, the synthetic utility of diazomethane is severely limited by its toxicity and highly explosive nature. Diazald® is typically used for ex situ synthesis, however it requires cumbersome and hazardous transfer of diazomethane from a caustic aqueous phase to the reaction medium. Herein, we present a low temperature and base‐free in situ synthesis of diazomethane via a “click and release” reaction between an enamine and sulfonyl azide. Its utility is exemplified by the synthesis of erse methyl esters in yields of up to 93%. Moreover, diazoketone synthesis from in situ generated diazomethane and acid chlorides was demonstrated for the first time. Finally, trideuteromethylation was achieved using acetone‐ d 6 as the deuterium source. We anticipate that this method will enable the safer use of diazomethane in organic synthesis and drug discovery programs.
Publisher: American Chemical Society (ACS)
Date: 21-12-2021
Publisher: American Chemical Society (ACS)
Date: 27-10-2017
Abstract: A convenient synthetic strategy toward N-acylguanidines via a sequential one-pot multicomponent carbonylation/amination reaction has been developed. The compounds were readily obtained via an N-cyanobenzamide intermediate formed from the Pd(0)-catalyzed carbonylative coupling of cyanamide and aryl iodides or bromides. Subsequent amination with a large variety of amines provided the final N-acylguanidines, with the overall formation of one C-C and two C-N bonds, in moderate to excellent yields. The substrate scope was found to be wide and the methodology was used to produce over 50 compounds, including 29 novel molecules. Furthermore, three separate nitrogen-containing heterocycles were prepared from the N-acylguanidines synthesized using the developed multicomponent, carbonylative method.
Publisher: American Chemical Society (ACS)
Date: 08-05-2019
Abstract: N-Acylsulfonamides represent an important bioisostere of carboxylic acids that allow for greater molecular elaboration and enhanced hydrogen bonding capabilities. Herein, we present a mild and convenient palladium(0)-catalyzed synthesis of N-acylsulfonamides via the carbonylative coupling of sulfonyl azides and electron-rich heterocycles. The reaction proceeds via in situ generation of a sulfonyl isocyanate followed by regioselective acylation of an indole or pyrrole nucleophile. This approach has been used to synthesize 34 indole- and pyrrole-substituted N-acylsulfonamides in yields of up to 95%. Importantly, this process is ligand-free and compatible with an ex situ solid CO source and requires only slightly elevated temperatures, making it a highly attractive method for the preparation of this important class of compounds. This study further investigated the possibility of labeling N-acylsulfonamides with carbon-11 to facilitate biological evaluation and in vivo studies with positron emission tomography.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7RP00009J
Abstract: To scaffold the development of problem-solving skills in chemistry, chemistry educators are exploring a variety of instructional techniques. In this study, we have designed, implemented, and evaluated a problem-solving workflow – “Goldilocks Help”. This workflow builds on work done in the field of problem solving in chemistry and provides specific scaffolding for students who experience procedural difficulties during problem solving, such as dead ends (not being able to troubleshoot) and false starts (not knowing how to initiate the problem-solving process). The Goldilocks Help workflow has been designed to scaffold a systematic problem-solving process with a designation of explicit phases of problem solving, to introduce students to the types of questions rompts that should guide them through the process, to encourage explicit reasoning necessary for successful conceptual problem solving, and to promote the development of metacognitive self-regulation skills. The tool has been implemented and evaluated over a two-year period and modified based on student and instructor feedback. The evaluation demonstrated a shift in students’ beliefs in their capacities to use the strategies required to achieve successful problem solving and showed their capacity to employ such strategies.
Publisher: American Chemical Society (ACS)
Date: 17-08-2020
Publisher: American Chemical Society (ACS)
Date: 13-04-2023
Publisher: American Chemical Society (ACS)
Date: 28-06-2019
DOI: 10.1021/ACS.JMEDCHEM.9B00757
Abstract: Aminopeptidase N (APN/CD13) is a zinc-dependent M1 aminopeptidase that contributes to cancer progression by promoting angiogenesis, metastasis, and tumor invasion. We have previously identified hydroxamic acid-containing analogues that are potent inhibitors of the APN homologue from the malarial parasite
Publisher: American Association for the Advancement of Science (AAAS)
Date: 06-01-2021
Abstract: l -DOPA–induced dyskinesia is caused by elevated l -DOPA levels and dysregulated l -DOPA metabolism throughout the brain.
Location: Sweden
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
No related grants have been discovered for Luke Schembri.