A5056551899- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Computational Drug Discovery Methods
- Malaria Research and Control
- Chemical Synthesis and Analysis
- Trypanosoma species research and implications
- Analytical Chemistry and Chromatography
- Synthesis and Catalytic Reactions
- HIV/AIDS drug development and treatment
- Mosquito-borne diseases and control
- Ubiquitin and proteasome pathways
- Synthesis and biological activity
- Phenothiazines and Benzothiazines Synthesis and Activities
- Machine Learning in Materials Science
- Innovative Microfluidic and Catalytic Techniques Innovation
- Coordination Chemistry and Organometallics
- Click Chemistry and Applications
- Inorganic and Organometallic Chemistry
University of Dundee
2023
University of York
2015-2022
LifeArc
2017-2019
To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We report here the results of a medicinal chemistry programme focused on an imidazopyridine series targeting Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG). The most potent compound (ML10) has IC
Fragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we describe a workflow design and synthesis of 56 3D disubstituted pyrrolidine piperidine fragments that occupy under-represented areas space (as demonstrated by principal moments inertia (PMI) analysis). A key, unique, underpinning feature this collection assessment shape...
Development of a class bicyclic inhibitors the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG), starting from known compounds with activity against related parasite PKG orthologue, is reported. Examination key sub-structural elements led to new good levels inhibitory recombinant and in vitro parasite. Key examples were shown possess encouraging ADME properties, computational analysis provided valuable insight into origins observed profiles.
Focussed studies on imidazopyridine inhibitors of Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG) have significantly advanced the series towards desirable in vitro property space. LLE-based approaches combining improvements cell potency, key physicochemical parameters and structural novelty are described, a structure-based design hypothesis relating to substituent regiochemistry has directed efforts examples with well-balanced ADME selectivity profiles.
Fragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we report synthesis of piperidine-based 3D building blocks - 20 regio- and diastereoisomers methyl substituted pipecolinates using simple general synthetic methods. cis-Piperidines, accessed through a pyridine hydrogenation were transformed into their trans-diastereoisomers...
Abstract Pan Assay INterference compoundS (PAINS) are known to be a source of false positives in High Throughput Screening (HTS) campaigns. This has become major problem medicinal chemistry, often resulting undesirable project outcomes and increased overall cost. Our recent campaign identify inhibitors USP8 that could used the treatment Parkinson’s disease identified several PAINS worked via variety mechanisms. Herein, we discuss process developed not only but also confirming interference...