2. Academic Validation
  3. Cyclopentane-based human NK1 antagonists. Part 2: development of potent, orally active, water-soluble derivatives

Cyclopentane-based human NK1 antagonists. Part 2: development of potent, orally active, water-soluble derivatives

  • Bioorg Med Chem Lett. 2006 Sep 1;16(17):4504-11. doi: 10.1016/j.bmcl.2006.06.044.
Laura C Meurer 1,  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,  Gary G Chicchi,  Linda A Egger,  Silvi Luell,  Joseph M Metzger,  D Euan Macintyre,  Nadia M J Rupniak,  Angela R Williams,  Richard J Hargreaves
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. [email protected]
PMID: 16831551 DOI: 10.1016/j.bmcl.2006.06.044
Abstract

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.

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