2. Academic Validation
  3. Cyclopentane-based human NK1 antagonists. Part 1: discovery and initial SAR

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

  • Bioorg Med Chem Lett. 2006 Sep 1;16(17):4497-503. doi: 10.1016/j.bmcl.2006.06.035.
Paul E Finke 1,  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,  D Euan Macintyre
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. [email protected]
PMID: 16824752 DOI: 10.1016/j.bmcl.2006.06.035
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 antagonist are described.

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