111493-62-0Relevant 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
supporting information, p. 10661 - 10675 (2016/12/16)
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.
SUBSTITUTED BICYCLOCARBOXYAMIDE COMPOUNDS
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Page/Page column 42, (2008/12/05)
This invention provides a compound of the formula (I). These compounds are useful for the treatment of disease conditions caused by overactivation of the VR1 receptor such as pain, or the like in mammal. This invention also provides a pharmaceutical composition comprising the above compound.
