Sulfide analogues of flupirtine and retigabine with nanomolar KV7.2/KV7.3 channel opening activity was written by Bock, Christian;Surur, Abdrrahman S.;Beirow, Kristin;Kindermann, Markus K.;Schulig, Lukas;Bodtke, Anja;Bednarski, Patrick J.;Link, Andreas. And the article was included in ChemMedChem in 2019.Name: 6-Chloro-5-methyl-3-nitropyridin-2-amine This article mentions the following:
The potassium channel openers flupirtine and retigabine have proven to be valuable analgesics or antiepileptics. Their recent withdrawal due to occasional hepatotoxicity and tissue discoloration, resp., leaves a therapeutic niche unfilled. Metabolic oxidation of both drugs gives rise to the formation of electrophilic quinones. These elusive, highly reactive metabolites may induce liver injury in the case of flupirtine and blue tissue discoloration after prolonged intake of retigabine. We examined which structural features can be altered to avoid the detrimental oxidation of the aromatic ring and shift oxidation toward the formation of more benign metabolites. Structure-activity relationship studies were performed to evaluate the KV7.2/3 channel opening activity of 45 derivatives Sulfide analogs were identified that are devoid of the risk of quinone formation, but possess potent KV7.2/3 opening activity. For example, flupirtine analog 3-(3,5-difluorophenyl)-N-(6-(isobutylthio)-2-(pyrrolidin-1-yl)pyridin-3-yl)propanamide (48) has 100-fold enhanced activity (EC50=1.4 n
6-Chloro-5-methyl-3-nitropyridin-2-amine (cas: 202217-19-4) belongs to pyridine derivatives. Pyridines are an important class of heterocycles and occur in polysubstituted forms in many naturally occurring biologically active compounds, drug molecules and chiral ligands. Pyridine, its benzo and pyridine-based compounds play diverse roles in organic chemistry. Pyridine-based materials are valued for their optical and physical properties as well as their medical potential. Name: 6-Chloro-5-methyl-3-nitropyridin-2-amine