Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis
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https://figshare.com/articles/dataset/Discovery_and_Optimization_of_a_Series_of_Pyrimidine_Based_Phosphodiesterase_10A_PDE10A_Inhibitors_through_Fragment_Screening_Structure_Based_Design_and_Parallel_Synthesis/2123962
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资源简介：
Screening of a fragment library for
PDE10A inhibitors identified
a low molecular 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 ip dosing.
创建时间：
2016-02-12
