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Meurer, Laura C.; Finke, Paul E.; Owens, Karen A.; Tsou, Nancy N.; Ball, Richard G.; Mills, Sander G.; MacCoss, Malcolm; Sadowski, Sharon; Cascieri, Margaret A.; Tsao, Kwei-Lan; Chicchi, Gary G.; Egger, Linda A.; Luell, Silvi; Metzger, Joseph M.; MacIntyre, D. Euan; Rupniak, Nadia M.J.; Williams, Angela R.; Hargreaves, Richard J.
Bioorganic & medicinal chemistry letters, 09/2006, Letnik: 16, Številka: 17Journal Article
The optimization of a cyclopentane-based hNK1 antagonist scaffold will be discussed in the context of enhanced water-solubility, sub-nanomolar hNK1 binding affinity, and oral activity in two in vivo models. The synthesis and optimization of a cyclopentane-based hNK1 antagonist scaffold 3, having four chiral centers, will be discussed in the context of its enhanced water solubility properties relative to the marketed anti-emetic hNK1 antagonist EMEND ® (Aprepitant). Sub-nanomolar hNK1 binding was achieved and oral activity comparable to Aprepitant in two in vivo models will be described.
