Obesity affects millions of people in the U.S. and worldwide, and this disease has enormous health and economic consequences for our society. Existing treatments show limited efficacy, can possess troubling side effects, and often require long-term therapy. Discovery of a new treatment for obesity would have very considerable scientific and commercial value. We have discovered an indole derivative possessing an encouraging pharmacological profile as a potential appetite suppressant. In Phase One, we propose to synthesize carefully selected analogs of this active lead compound. The pharmacology of these compounds will be evaluated both in vitro and in vivo. From this project we specifically aim to discover one or more indole analogs showing efficacy in an animal model for appetite suppression comparable to that of established therapies. Such a result will strongly support continuation in Phase Two. The long-term goal of this project is to discover new, improved treatments for obesity.