Potent, Selective, and CNS-Penetrant Tetrasubstituted Cyclopropane Class Ila Histone Deacetylase (HDAC) Inhibitors

Potent and selective class Ha HDAC tetrasubstituted cyclopropane hydroxamic acid inhibitors were identified with high oral bioavailability that exhibited good brain and muscle exposure. Compound 14 displayed suitable properties for assessment of the impact of class Ha HDAC catalytic site inhibition in preclinical disease models.