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ID: ALA3853331

Journal: J Med Chem

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

Authors: Remen L, Bezençon O, Simons L, Gaston R, Downing D, Gatfield J, Roch C, Kessler M, Mosbacher J, Pfeifer T, Grisostomi C, Rey M, Ertel EA, Moon R.

Abstract: 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.

CiteXplore: 27579577

DOI: 10.1021/acs.jmedchem.6b00756