University of Virginia Patent Foundation

Virginia Tech Intellectual Properties, Inc.

Yumin Dai

Webster L Santos

Kyle Hoehn

Jose A Santiago-Rivera

Elizabeth S Childress

Jacob Murray

Jacob H Murray

Jose Santiago-rivera

This disclosure provides compounds of Formula I, II, and III and pharmaceutically acceptable salts thereof for use as mitochondrial uncouplers, where the variables, e.g. R-R, X, X, and Yare defined in the specification. The disclosure also provides pharmaceutical compositions comprising a compound or pharmaceutically acceptable salt of Formula I, II, or III, alone or in combination with another active compound. Compounds and compositions of Formula I, II, and III are useful for treating or preventing certain conditions such as obesity, type II diabetes, fatty liver disease, insulin resistance, Parkinson's disease, ischemia reperfusion injury, heart failure, non-alcoholic fatty liver disease (NALFD), and non-alcoholic steatohepatitis (NASH). Compounds of Formula I, II, and III are also useful for regulating glucose homeostatis and insulin action.

Compositions and methods for preparing and using mitochondrial uncouplers

The disclosure provides compounds of Formula (I-A) and (I-B) and the pharmaceutically acceptable salts thereof. The variables, R, R, R, X, X, X, Y, Y, and Z are defined herein. Certain compounds of Formula (I-A) and (I-B) act as selective mitochondrial protonophore uncouplers that do not affect plasma membrane potential. These compounds are useful for treating or decreasing 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, non-alcoholic fatty liver disease (NALFD), and non-alcoholic steatohepatitis (NASH), Because mitochondrial uncouplers decrease the production of reactive oxygen species (ROS), which are known to contribute to age-related cell damage, the compounds are useful for increasing lifespan. Compounds and salts of Formulae (I-A) and (I-B) are also useful for regulating glucose homeostasis or insulin action in a patient.

Substituted imidazo[4,5-b]pyridines, imidazo[4,5-b]pyrazines, and oxazolo[4,5- b]pyrazines as mitochondrial uncouplers

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Blacksburg, VA, United States of America

Yumin Dai