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The synthesis and antibacterial activities of three chemotypes of DNA supercoiling inhibitors based on imidazolo[1,2-a]pyridine and [1,2,4]triazolo[1,5-a]pyridine scaffolds that target the ATPase subunits of DNA gyrase and topoisomerase IV (GyrB/ParE) is reported. The most potent scaffold was selected for optimization leading to a series with potent Gram-positive antibacterial activity and a low resistance frequency.

A series of analogues of the peptide deformylase (PDF) inhibitor BB-3497 where the P3' amide bond was replaced with a ketone functionality is described. The in vitro antibacterial profiling of these compounds revealed that they demonstrate activity against pathogens associated with respiratory tract infections.

A series of N-formyl hydroxylamine peptide deformylase inhibitors containing a cyclic azaamino acid moiety between the P1' and P3' substituents are presented. Selected compounds display antibacterial activity against pathogens associated with respiratory tract infections with representative compounds showing excellent MICs against Haemophilus influenzae.

A high-throughput screening campaign identified 4-((E)-styryl)-pyrimidin-2-ylamine (11) as a positive allosteric modulator of the metabotropic glutamate (mGlu) receptor subtype 4. An evaluation of the structure-activity relationships (SAR) of 11 is described and the efficacy of this compound in a haloperidol-induced catalepsy rat model following oral administration is presented.

3-Methoxybenzamide is a weak inhibitor of the essential bacterial cell division protein FtsZ. Exploration of the structure-activity relationships of 3-methoxybenzamide analogues led to the identification of potent anti-staphylococcal compounds.

A high-throughput screening campaign resulted in the discovery of a highly potent dual cannabinoid receptor 1 (CB1) and 2 (CB2) agonist. Following a thorough SAR exploration, a series of selective CB2 full agonists were identified.

Structure-guided de novo drug design led to the identification of a novel series of substituted pyridine derivatives as HIF-1alpha prolyl hydroxylase inhibitors. Pyridine carboxyamide derivatives bearing a substituted aryl group at the 5-position of the pyridine ring show appreciable activity, while constraining the side chain by placing a pyrazole carboxylic acid generated a potent lead series with consistent activity against EGLN-1.

A series of analogues of the potent peptide deformylase (PDF) inhibitor BB-3497 containing alternative metal binding groups was synthesised. Enzyme inhibition and antibacterial activity data for these compounds revealed that the bidentate hydroxamic acid and N-formyl hydroxylamine structural motifs represent the optimum chelating groups on the pseudopeptidic BB-3497 backbone.