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Orally active and brain permeable proline amides as highly selective 5HT2c agonists for the treatment of obesity.

Kevin K-C Liu, Bruce A Lefker, Mark A Dombroski, Phoebe Chiang, Peter Cornelius, Terrell A Patterson, Yuan Zeng, Stephanie Santucci, Elizabeth Tomlinson, Colleen P Gibbons, Ravi Marala, Janice A Brown, Jimmy X Kong, Eunsun Lee, Wendy Werner, Zane Wenzel, Craig Giragossian, Hou Chen, Steven B Coffey
Bioorganic & Medicinal Chemistry Letters 2010 April 2
Brain-penetrable proline amides were developed as 5HT2c agonists with more than 1000-fold binding selectivity against 5HT2b receptor. After medicinal chemistry optimization and SAR studies, orally active proline amides with robust efficacy in a rodent food intake inhibition model were uncovered.

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