| abstract |
OXADIAZOLOPYRAZINS AND OXADIAZOLOPYRIDINES USEFUL AS MITOCHONDRIAL DETACHERS. The disclosure provides compounds of Formula I and the pharmaceutically acceptable salts thereof. The variables R1, R2, R3, X1, X2, and Z are defined here. Certain Formula I compounds act as selective mitochondrial protonophor decouplers that do not affect the potential of the plasma membrane. Formula I compounds and salts are useful to treat or decrease the risk of conditions responsive to mitochondrial decoupling, such as cancer, obesity, type II diabetes, fatty liver disease, insulin resistance, Parkinson's disease, ischemic reperfusion injury, heart failure, alcoholic fatty liver disease (NALFD) and non-alcoholic steatohepatitis (NASH). Since mitochondrial decouplers decrease the production of reactive oxygen species (ROS), which are known to contribute to age-related cell damage, Formula I compounds are useful for increasing life expectancy. Formula I compounds and salts are also useful for regulating glucose homeostasis or insulin action in a patient. |