Cyclic urea derivatives as potent NK1 selective antagonists

2006 Imidazole derivatives R 0190 Cyclic Urea Derivatives as Potent NK1 Selective Antagonists. Part 2. Effects of Fluoro and Benzylic Methyl Substitutions. — Introduction of an α-methyl group at 19- 106 the benzylic position and of a p-fluoro group at the phenyl ring of a potent and selective NK1 receptor antagonist improves duration of in vivo activity. The α-methyl substitution provides a significant enhancement in binding affinity. Urea derivatives (VIII) and (X) retain good brain penetration and display improved potency and duration of oral in vivo activity compared to the original lead. — (PALIWAL*, S.; et al.; Bioorg. Med. Chem. Lett. 16 (2006) 4, 1065-1069; Dep. Chem. Res., Schering-Plough Res. Inst., Kenilworth, NJ 07033, USA; Eng.) — H. Hoennerscheid