Discovery of a biarylamide series of potent, state-dependent NaV1.7 inhibitors was written by Schenkel, Laurie B.;DiMauro, Erin F.;Nguyen, Hanh N.;Chakka, Nagasree;Du, Bingfan;Foti, Robert S.;Guzman-Perez, Angel;Jarosh, Michael;La, Daniel S.;Ligutti, Joseph;Milgram, Benjamin C.;Moyer, Bryan D.;Peterson, Emily A.;Roberts, John;Yu, Violeta L.;Weiss, Matthew M.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2017.Electric Literature of C6H3BrF3N This article mentions the following:
State-dependent NaV1.7 inhibitors. The NaV1.7 ion channel has garnered considerable attention as a target for the treatment of pain. Herein we detail the discovery and structure-activity relationships of a novel series of biaryl amides. Optimization led to the identification of several state-dependent, potent and metabolically stable inhibitors which demonstrated promising levels of selectivity over NaV1.5 and good rat pharmacokinetics. Compound I, which demonstrated preferential inhibition of a slow inactivated state of NaV1.7, was advanced into a rat formalin study where upon reaching unbound drug levels several fold over the rat NaV1.7 IC50 it failed to demonstrate a robust reduction in nociceptive behavior. In the experiment, the researchers used many compounds, for example, 2-Bromo-3-(trifluoromethyl)pyridine (cas: 175205-82-0Electric Literature of C6H3BrF3N).
2-Bromo-3-(trifluoromethyl)pyridine (cas: 175205-82-0) belongs to pyridine derivatives. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. Reduced pyridines, namely tetrahydropyridines, dihydropyridines and piperidines, are found in numerous natural and synthetic compounds. The synthesis and reactivity of these compounds have often been driven by the fact many of these compounds have interesting and unique pharmacological properties. Electric Literature of C6H3BrF3N