Pyrrolidine-carboxamides and oxadiazoles as potent hNK1 antagonists

  • Bioorg Med Chem Lett. 2007 Oct 1;17(19):5310-5. doi: 10.1016/j.bmcl.2007.08.028.
Jonathan R Young  1 ,  Ronsar Eid ,  Cherilyn Turner ,  Robert J DeVita ,  Marc M Kurtz ,  Kwei-Lan C Tsao ,  Gary G Chicchi ,  Alan Wheeldon ,  Emma Carlson ,  Sander G Mills
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, PO 2000, Rahway, NJ 07065-0900, USA. [email protected]
PMID: 17723300 DOI: 10.1016/j.bmcl.2007.08.028
Abstract

The preparation and structure-activity-relationships of novel pyrrolidine-carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK(1) antagonists in vitro and efficacious in vivo with minimal interactions with P(450) liver Enzymes. Oxadiazole analog 22 was determined to have excellent hNK(1) binding affinity, functional activity, and a good PD response in vivo.