Preparation, Antiepileptic Activity, and Cardiovascular Safety of Dihydropyrazoles as Brain-Penetrant T‑Type Calcium Channel Blockers

A series of dihydropyrazole
derivatives was developed as potent,
selective, and brain-penetrating T-type calcium channel blockers.
An optimized derivative, compound 6c, was advanced to
in vivo studies, where it demonstrated
efficacy in the WAG/Rij rat model of generalized nonconvulsive, absence-like
epilepsy. Compound 6c was not efficacious in the basolateral
amygdala kindling rat model of temporal lobe epilepsy, and it led
to prolongation of the PR interval in ECG recordings in rodents.