A series of novel 2-azabicyclo[2.2.2]octane derivatives was synthesized and evaluated as long chain fatty acid elongase 6 (ELOVL6) inhibitors. Screening of our corporate chemical collections against ELOVL6 resulted in the identification of lead 1. Exploratory chemistry efforts were applied to lead 1 to identify the orally available, potent, and selective ELOVL6 inhibitor 28a.
