Discovery of a novel, potent and orally active series of γ-lactams as selective NK 1 antagonists

Abstract

Strategic replacement of the nitrogen of the lead compound 1 in the original cyclic urea series with a carbon resulted in the discovery of a novel, potent and orally more efficacious γ-lactam series of selective NK 1 antagonists. Optimization of the lactam series culminated in the identification of compounds with high binding affinity and excellent oral CNS activity.