Anilinopyrazines as potential mitochondrial uncouplers

摘要: Mitochondrial protonophores transport protons through the mitochondrial inner membrane into matrix to uncouple nutrient oxidation from ATP production thereby decreasing proton motive force. uncouplers have beneficial effects of decrease reactive oxygen species generation and potential for treating diseases such as obesity, neurodegenerative diseases, non-alcoholic fatty liver disease (NAFLD), diabetes, many others. In this study, we report structure-activity relationship profile pyrazine scaffold bearing substituted aniline rings. Our work indicates that a trifluoromethyl group is best at para position while trifluoromethoxy preferred in meta rings 2,3-substituted pyrazines. As cycling requires formation negative charge has traverse membrane, stabilizing internal hydrogen bond key feature efficient uncoupling activity.