Obesity has become a serious health concern in the US as two thirds of the population are considered either overweight or obese. Targeting the mitochondria shows promise for the treatment of obesity and obesity-related diseases. ATP production takes place in the mitochondria with nutrient oxidation being coupled to oxidative phosphorylation. A small molecule capable of shuttling protons from the mitochondrial inner membrane space to the mitochondrial core, in favor of the electrochemical gradient of the proton motive force, can decouple nutrient oxidation to ATP production. This renders oxidative phosphorylation inefficient, requiring more nutrient oxidation. Previous small molecule mitochondrial uncouplers have shown weight-loss properties, but their benefits have been overshadowed by side effects resulting from poor selectivity towards the mitochondrial inner membrane. Recently, the discovery of mitochondrial uncoupler BAM15 opened a field for the study of compounds that lack off-target effects and exhibit a broader therapeutic window. Herein, a structure-activity relationship study was conducted using imidazole-pyrazine derivatives as potential mitochondrial uncouplers. Compounds were initially screened using an oxygen consumption assay and results were obtained with compounds displaying favorable uncoupling capability and pharmacokinetic properties in mice. These discoveries provide a field for the treatment of obesity that can be further explored.<br/>

Uncouplers of oxidative phosphorylation as obesity therapeutics

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.