| abstract |
The present disclosure provides compounds of formulae (I-A) and (I-B) and pharmaceutically acceptable salts thereof. The variables R, R2, R3 , X1, X2 , X3 , Y1 , Y, and Z are defined herein . Certain compounds of formula (I-A) and (I-B) are useful as selective mitochondrial proton carrier uncouplers that do not affect plasma membrane potential. These compounds can be used to treat or reduce the risk of conditions responsive to mitochondrial uncoupling, such as cancer, obesity, type II diabetes, fatty liver disease, insulin resistance, Parkinson's disease, ischemia-reperfusion injury, Heart failure, nonalcoholic fatty liver disease (NALFD), or nonalcoholic steatohepatitis (NASH). Since mitochondrial uncouplers reduce the production of reactive oxygen species (ROS), which are known to cause age-related cellular damage, the compounds can be used to extend lifespan. The compounds and salts of formulae (I-A) and (I-B) are also useful for modulating glucose homeostasis or insulin action in patients. |