Shipe, William D.; Sharik, Steven S.; Barrow, James C.; McGaughey, Georgia B.; Theberge, Cory R.; Uslaner, Jason M.; Yan, Youwei; Renger, John J.; Smith, Sean M.; Coleman, Paul J.; Cox, Christopher D. published the artcile< Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis>, Application In Synthesis of 56622-54-9, the main research area is pyrimidine derivative PDE10A inhibitor screening discovery preparation structure.
Screening of a fragment library for PDE10A inhibitors identified a low mol. weight pyrimidine hit with PDE10A Ki of 8700 nM and LE of 0.59. Initial optimization by catalog followed by iterative parallel synthesis guided by X-ray cocrystal structures resulted in rapid potency improvements with minimal loss of ligand efficiency. Compound 15h, with PDE10A Ki of 8.2 pM, LE of 0.49, and >5000-fold selectivity over other PDEs, fully attenuates MK-801-induced hyperlocomotor activity after i.p. dosing.
Journal of Medicinal Chemistry published new progress about Antipsychotics. 56622-54-9 belongs to class pyridine-derivatives, and the molecular formula is C7H10N2, Application In Synthesis of 56622-54-9.