Cyclopentane-based human NK1 antagonists. Part 1: Discovery and initial SAR
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- 作者：Paul E. Finke ; Laura C. Meurer ; Dorothy A. Levorse ; Sander G. Mills ; Malcolm MacCoss ; Sharon Sadowski ; Margaret A. Cascieri ; Kwei-Lan Tsao ; Gary G. Chicchi ; Joseph M. Metzger and D. Euan MacIntyre
- 关键词：Neurokinin-1 receptor ; 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：4497-4503
- 全文大小：163 K
文摘
An initial investigation of the novel cyclopentane scaffold 6 afforded low nanomolar human NK1 antagonists having enhanced water solubility properties compared to morpholine 1. A synthesis of this cyclopentane scaffold, having three contiguous chiral centers, and the unexpected determination that the 1,2-trans-2,3-trans-ring stereochemistry, as opposed to the cis-ether/phenyl configuration of the known structures 1–5, is optimal for this class of antagonist are described.