Jonathan M. Large
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View article: Design and Synthesis of Pyrazoline Inhibitors of SARS-CoV-2 NSP14
Design and Synthesis of Pyrazoline Inhibitors of SARS-CoV-2 NSP14 Open
Non-structural protein 14 (NSP14) is a key two-domain protein responsible for maintaining coronavirus replication fidelity, and in its absence reproduction is severely impacted. With the goal of identifying new inhibitors of SARS-CoV-2 NSP…
View article: XAT‐Catalysis for Intramolecular Biaryl Synthesis
XAT‐Catalysis for Intramolecular Biaryl Synthesis Open
Radical ipso‐ substitution offers an alternative to organometallic approaches for biaryl synthesis, but usually requires stoichiometric reagents such as tributyltin hydride. Here, we demonstrate that visible light photoredox catalysis can …
View article: XAT‐Catalysis for Intramolecular Biaryl Synthesis
XAT‐Catalysis for Intramolecular Biaryl Synthesis Open
Radical ipso‐ substitution offers an alternative to organometallic approaches for biaryl synthesis, but usually requires stoichiometric reagents such as tributyltin hydride. Here, we demonstrate that visible light photoredox catalysis can …
View article: Targeted protein degradation in CNS disorders: a promising route to novel therapeutics?
Targeted protein degradation in CNS disorders: a promising route to novel therapeutics? Open
Targeted protein degradation (TPD) is a rapidly expanding field, with various PROTACs (proteolysis-targeting chimeras) in clinical trials and molecular glues such as immunomodulatory imide drugs (IMiDs) already well established in the trea…
View article: CCDC 2244918: Experimental Crystal Structure Determination
CCDC 2244918: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: CCDC 2253675: Experimental Crystal Structure Determination
CCDC 2253675: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: CCDC 2253673: Experimental Crystal Structure Determination
CCDC 2253673: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: CCDC 2244917: Experimental Crystal Structure Determination
CCDC 2244917: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: Aryne‐Enabled C−N Arylation of Anilines
Aryne‐Enabled C−N Arylation of Anilines Open
Anilines are potentially high‐value arylating agents, but are limited by the low reactivity of the strong C−N bond. We show that the reactive intermediate benzyne can be used to both activate anilines, and set‐up an aryl transfer reaction …
View article: Aryne‐Enabled C−N Arylation of Anilines
Aryne‐Enabled C−N Arylation of Anilines Open
Anilines are potentially high‐value arylating agents, but are limited by the low reactivity of the strong C−N bond. We show that the reactive intermediate benzyne can be used to both activate anilines, and set‐up an aryl transfer reaction …
View article: CCDC 2277255: Experimental Crystal Structure Determination
CCDC 2277255: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: CCDC 2277260: Experimental Crystal Structure Determination
CCDC 2277260: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: Synthesis of Functionalized Pyrrolidinone Scaffolds via Smiles-Truce Cascade
Synthesis of Functionalized Pyrrolidinone Scaffolds via Smiles-Truce Cascade Open
Arylsulfonamides have been found to react with cyclopropane diesters under simple base treatment to give α-arylated pyrrolidinones. This one-pot process comprises three steps: nucleophilic ring-opening of the cyclopropane, reaction of the …
View article: Diarylamine Synthesis via Desulfinylative Smiles Rearrangement
Diarylamine Synthesis via Desulfinylative Smiles Rearrangement Open
Diarylamines are obtained directly from sulfinamides through a novel rearrangement sequence. The transformation is transition metal-free and proceeds under mild conditions, providing facile access to highly sterically hindered diarylamines…
View article: Aprepitant is a novel, selective activator of the K2P channel TRAAK
Aprepitant is a novel, selective activator of the K2P channel TRAAK Open
TRAAK (KCNK4, K2P4.1) is a mechanosensitive two-pore domain potassium (K2P) channel. Due to its expression within sensory neurons and genetic link to neuropathic pain it represents a promising potential target for novel analgesics. In comm…
View article: A “Target Class” Screen to Identify Activators of Two-Pore Domain Potassium (K2P) Channels
A “Target Class” Screen to Identify Activators of Two-Pore Domain Potassium (K2P) Channels Open
Two-pore domain potassium (K2P) channels carry background (or leak) potassium current and play a key role in regulating resting membrane potential and cellular excitability. Accumulating evidence points to a role for K2Ps in human pathophy…
View article: Targeting the Malaria Parasite cGMP-Dependent Protein Kinase to Develop New Drugs
Targeting the Malaria Parasite cGMP-Dependent Protein Kinase to Develop New Drugs Open
The single-celled apicomplexan parasite Plasmodium falciparum is responsible for the majority of deaths due to malaria each year. The selection of drug resistance has been a recurring theme over the decades with each new drug that is devel…
View article: Pranlukast is a novel small molecule activator of the two-pore domain potassium channel TREK2
Pranlukast is a novel small molecule activator of the two-pore domain potassium channel TREK2 Open
TREK2 (KCNK10, K2P10.1) is a two-pore domain potassium (K2P) channel and a potential target for the treatment of pain. Like the majority of the K2P superfamily, there is currently a lack of useful pharmacological tools to study TREK2. Here…
View article: Developing an Antibody–Drug Conjugate Approach to Selective Inhibition of an Extracellular Protein
Developing an Antibody–Drug Conjugate Approach to Selective Inhibition of an Extracellular Protein Open
Antibody–drug conjugates (ADCs) are a growing class of therapeutics that harness the specificity of antibodies and the cell‐killing potency of small‐molecule drugs. Beyond cytotoxics, there are few examples of the application of an ADC app…
View article: Potent inhibitors of malarial P. Falciparum protein kinase G: Improving the cell activity of a series of imidazopyridines
Potent inhibitors of malarial P. Falciparum protein kinase G: Improving the cell activity of a series of imidazopyridines Open
Development of a class of bicyclic inhibitors of the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG), starting from known compounds with activity against a related parasite PKG orthologue, is reported. Examination of key …