The discovery of 2-fluoro-N-(3-fluoro-4-(5-((4-morpholinobutyl)amino)-1,3,4-oxadiazol-2-yl)phenyl)benzamide, a full agonist of the alpha-7 nicotinic acetylcholine receptor showing efficacy in the novel object recognition model of cognition enhancement.

A series of α7 nicotinic acetylcholine receptor full agonists with a 1,3,4-oxadiazol-2-amine core has been discovered. Early lead 1 was found to have a limited therapeutic index with respect to its potential for cardiovascular side effects. Further optimisation of this series led to the identification of 22 a potent full agonist showing efficacy at a dose of 0.

Identification of a series of 1,3,4-oxadiazol-2-amines as potent alpha-7 agonists with efficacy in the novel object recognition model of cognition.

A series of α7 nicotinic acetylcholine receptor full-agonists with a 1,3,4-oxadiazol-2-amine core has been discovered. Systematic exploration of the structure-activity relationships for both α7 potency and selectivity with respect to interaction with the hERG channel are described. Further profiling led to the identification of compound 22, a potent full agonist showing efficacy in the novel object recognition model of cognition enhancement.

Aryl sulphonyl amides as potent agonists of the growth hormone secretagogue (ghrelin) receptor.

As part of an on-going lead optimisation effort, a cross screening exercise identified an aryl sulphonyl amide hit that was optimised to afford a highly potent series of ghrelin receptor agonists.

Pyridone derivatives as potent, orally bioavailable VLA-4 integrin antagonists.

A series of pyridone-N-benzyl-propanoic acids have been optimised to afford potent orally bioavailable VLA-4 antagonists.

Pyridone derivatives as potent and selective VLA-4 integrin antagonists.

A novel series of pyridone inhibitors has been identified through pharmacophore analysis, as potent antagonists of VLA-4.

6-heteroaryl-pyrazolo[3,4-b]pyridines: potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3).

A series of 6-heteroaryl-pyrazolo[3,4-b]pyridines has been optimised to afford potent inhibitors of Glycogen Synthase Kinase-3 (GSK-3). These analogues display excellent selectivity over the closely related Cyclin Dependent Kinase-2 (CDK-2).

6-aryl-pyrazolo[3,4-b]pyridines: potent inhibitors of glycogen synthase kinase-3 (GSK-3).

A novel series of 6-aryl-pyrazolo[3,4-b]pyridines has been identified that are potent inhibitors of glycogen synthase kinase-3 (GSK-3).

5-aryl-pyrazolo[3,4-b]pyridazines: potent inhibitors of glycogen synthase kinase-3 (GSK-3).

Introduction of a nitrogen atom into the 6-position of a series of pyrazolo[3,4-b]pyridines led to a dramatic improvement in the potency of GSK-3 inhibition. Rationalisation of the binding mode suggested participation of a putative structural water molecule, which was subsequently confirmed by X-ray crystallography.

5-aryl-pyrazolo[3,4-b]pyridines: potent inhibitors of glycogen synthase kinase-3 (GSK-3).

A novel series of pyrazolo[3,4-b]pyridines has been identified that are potent inhibitors of glycogen synthase kinase-3 (GSK-3).