Cyclic urea derivatives as potent NK 1 selective antagonists. Part II: Effects of fluoro and benzylic methyl substitutions

…, H Wang, JJ Piwinski, RA Duffy, JE Lachowicz…

Index: Shue, Ho-Jane; Chen, Xiao; Schwerdt, John H.; Paliwal, Sunil; Blythin, David J.; Lin, Ling; Gu, Danlin; Wang, Cheng; Reichard, Gregory A.; Wang, Hongwu; Piwinski, John J.; Duffy, Ruth A.; Lachowicz, Jean E.; Coffin, Vicki L.; Nomeir, Amin A.; Morgan, Cynthia A.; Varty, Geoffrey B.; Shih, Neng-Yang Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 4 p. 1065 - 1069

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Citation Number: 41

Abstract

A series of novel five-membered urea derivatives as potent NK1 receptor antagonists is described. The effects of substitution of a 4-fluoro group at the phenyl ring and the introduction of an α-methyl group at the benzylic position to improve potency and duration of in vivo activity are discussed. Several compounds with high affinity and sustained in vivo activity were identified.