Neil Moorcroft

Mapping the kinase domain of Janus Kinase 3.

The utilization and impact of parallel synthesis on lead exploration around initial hit oxindole (1) are described. The emergent SAR, analogue design and functional impact will also be detailed.

Phosphorus–nitrogen–phosphorus ligands: cooperative effects between nitrogen and phosphorus substituents on catalytic activity

A new generation of PNP compounds bearing different diarylphosphine groups were prepared and used as ligands in palladium-catalysed Suzuki cross-coupling reactions. Rates of oxidative addition of iodobenzene to (PNP)Pd[0] complexes were measured using UV spectroscopy. Synergistic effects between the N- and P- substituents were identified and correlated in redox and catalytic chemistry.

Design and synthesis of D1 agonist/D2 antagonist for treatment of schizophrenia

A series of tetrahydroisoquinolines were designed, synthesized and evaluated as the first non-natural product type of compounds with dual D(1) receptor (D(1)R) agonism and D(2) receptor (D(2)R) antagonism properties for treatment of schizophrenia. The initial SAR of the series was explored. The lead in the series, 3g, exhibited high affinity and good potency. Compound 3g displayed 95% of D(1)R occupancy (10 mg/kg, sc) and 75% of D(2)R occupancy (10 mg/kg, sc) in the striatum of male CD-1 mice. The series exhibited unique pharmacology and merit as tool compounds for target validation and future optimizations.