Flupirtine and retigabine as templates for ligand-based drug design of KV7.2/3 activators was written by Surur, Abdrrahman S.;Bock, Christian;Beirow, Kristin;Wurm, Konrad;Schulig, Lukas;Kindermann, Markus K.;Siegmund, Werner;Bednarski, Patrick J.;Link, Andreas. And the article was included in Organic & Biomolecular Chemistry in 2019.Synthetic Route of C6H6ClN3O2 This article mentions the following:
Drug induced liver injury (DILI) and tissue discoloration led to the recent discontinuation of the therapeutic use of the closely related drugs flupirtine and retigabine, resp. Experience gained with these drugs strongly suggests that heterotetramer, voltage-gated potassium channels 2 and 3 (KV7.2/3) are valid targets for effective treatment of pain and epilepsy. Because the adverse effects are not related to the mechanism of action, it appears promising to investigate chem. modifications of these clin. validated, drug-like leads. In the present retro-metabolic drug design study, a series of 43 compounds were synthesized and characterized with regard to KV7.2/3 opening activity and efficacy. The most active compound I displays excellent potency (EC50 = 4 nM) and efficacy (154%) as a KV7.2/3 opener. Limited aqueous solubility hampered toxicity testing at concentrations higher than 63 μM, but this concentration was nontoxic to two hepatocellular cell lines (HEP-G2 and TAMH) in culture. The slightly less active but more soluble compound II (EC50 = 11 nM, efficacy 111%) showed an improved toxicity/activity ratio compared to flupirtine by three orders of magnitude and represents an attractive lead structure for the development of safer analgesics and antiepileptics. In the experiment, the researchers used many compounds, for example, 6-Chloro-5-methyl-3-nitropyridin-2-amine (cas: 202217-19-4Synthetic Route of C6H6ClN3O2).
6-Chloro-5-methyl-3-nitropyridin-2-amine (cas: 202217-19-4) belongs to pyridine derivatives. Pyridine is diamagnetic and has a diamagnetic susceptibility of â?8.7 à 10â? cm3·molâ?.The molecular electric dipole moment is 2.2 debyes. The standard enthalpy of formation is 100.2 kJ·molâ? in the liquid phase and 140.4 kJ·molâ? in the gas phase. 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. Synthetic Route of C6H6ClN3O2