352356-41-3Relevant academic research and scientific papers
Structure-Activity Relationship, Drug Metabolism and Pharmacokinetics Properties Optimization, and in Vivo Studies of New Brain Penetrant Triple T-Type Calcium Channel Blockers
Siegrist, Romain,Pozzi, Davide,Jacob, Ga?l,Torrisi, Caterina,Colas, Kilian,Braibant, Bertrand,Mawet, Jacques,Pfeifer, Thomas,De Kanter, Ruben,Roch, Catherine,Kessler, Melanie,Corminboeuf, Olivier,Bezen?on, Olivier
, p. 10661 - 10675 (2016)
Despite the availability of numerous antiepileptic drugs, 20-30% of epileptic patients are pharmacoresistant with seizures not appropriately controlled. Consequently, new strategies to address this unmet medical need are required. T-type calcium channels play a key role in neuronal excitability and burst firing, and selective triple T-type calcium channel blockers could offer a new way to treat various CNS disorders, in particular epilepsy. Herein we describe the identification of new 1,4-benzodiazepines as brain penetrant and selective triple T-type calcium channel blockers. From racemic hit 4, optimization work led to the preparation of pyridodiazepine 31c with improved physicochemical properties, solubility, and metabolic stability. The racemic mixture was separated by chiral preparative HPLC, and the resulting lead compound (3R,5S)-31c showed promising efficacy in the WAG/Rij-rat model of generalized nonconvulsive absence-like epilepsy.
Benzene-fused heterocycle derivatives and drugs containing the same as the active ingredient
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, (2008/06/13)
A benzene-fused heteroring derivative of formula (I) 1, wherein all symbols are the same as described in the specification, and a non-toxic salt thereof. The compound of formula (I) has an inhibitory activity against cysteine protease and therefore it is
