Cyclopentane-based human NK1 antagonists. Part 1: Discovery and initial SAR

…, M MacCoss, S Sadowski, MA Cascieri, KL Tsao…

Index: Finke, Paul E.; Meurer, Laura C.; Levorse, Dorothy A.; Mills, Sander G.; MacCoss, Malcolm; Sadowski, Sharon; Cascieri, Margaret A.; Tsao, Kwei-Lan; Chicchi, Gary G.; Metzger, Joseph M.; MacIntyre, D. Euan Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 17 p. 4497 - 4503

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Citation Number: 27

Abstract

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 ...