Pyrrolidine-carboxamides and oxadiazoles as potent hNK₁ antagonists

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• 作者：Jonathan R. Young ; Ronsar Eid ; Cherilyn Turner ; Robert J. DeVita ; Marc M. Kurtz ; Kwei-Lan C. Tsao ; Gary G. Chicchi ; Alan Wheeldon ; Emma Carlson ; S ; er G. Mills
• 关键词：NK₁ antagonists ; Substance P
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2007
• 出版时间：1 October 2007
• 年：2007
• 卷：17
• 期：19
• 页码：5310-5315
• 全文大小：185 K

文摘

The preparation and structure–activity-relationships of novel pyrrolidine-carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK₁ antagonists in vitro and efficacious in vivo with minimal interactions with P₄₅₀ liver enzymes. Oxadiazole analog 22 was determined to have excellent hNK₁ binding affinity, functional activity, and a good PD response in vivo.