Cyclopentane-based human NK1 antagonists. Part 2: Development of potent, orally active, water-soluble derivatives
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- 作者：Laura C. Meurer ; Paul E. Finke ; Karen A. Owens ; Nancy N. Tsou ; Richard G. Ball ; Sander G. Mills ; Malcolm MacCoss ; Sharon Sadowski ; Margaret A. Cascieri ; Kwei-Lan Tsao et al.
- 关键词：Neurokinin-1 ; substance P ; NK1 antagonist ; cyclopentane-based structure
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2006
- 出版时间：1 September 2006
- 年：2006
- 卷：16
- 期：17
- 页码：4504-4511
- 全文大小：249 K
文摘
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.