Siegrist, Romain; Pozzi, Davide; Jacob, Gael; Torrisi, Caterina; Colas, Kilian; Braibant, Bertrand; Mawet, Jacques; Pfeifer, Thomas; de Kanter, Ruben; Roch, Catherine; Kessler, Melanie; Corminboeuf, Olivier; Bezencon, Olivier published their research in Journal of Medicinal Chemistry on December 8 ,2016. The article was titled 《Structure-Activity Relationship, Drug Metabolism and Pharmacokinetics Properties Optimization, and in Vivo Studies of New Brain Penetrant Triple T-Type Calcium Channel Blockers》.Computed Properties of C5H2ClN3 The article contains the following contents:
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 the authors describe the identification of new 1,4-benzodiazepines as brain penetrant and selective triple T-type calcium channel blockers. From racemic hit 4 ((±)-N,1-dibenzyl-3,5-cis-dimethyl-1,2,3,5-tetrahydro-4H-benzo[e][1,4]diazepine-4-carboxamide), optimization work led to the preparation of pyridodiazepine 31c with improved physicochem. properties, solubility and metabolic stability. The racemic mixture was separated by chiral preparative HPLC and the resulting lead compound (3R,5S)-31c ((3R,5S)-N,1-dibenzyld-3,5-dimethyl-1,2,3,5-tetrahydro-4,5-pyrido[3,4-e][1,4]diazepine-4-carboxamide) showed promising efficacy in the WAG/Rij-rat model of generalized non-convulsive absence-like epilepsy. In the experiment, the researchers used many compounds, for example, 3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3Computed Properties of C5H2ClN3)
3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3) belongs to pyridazine derivatives.The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. Pyridazines are also important because of their utility in synthetic organic chemistry and in physical organic chemistry.There are reports available for the synthesis of pyridazine and their derivatives by using 2-oxoaldehyes.Computed Properties of C5H2ClN3
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem