N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists

  • Bioorg Med Chem Lett. 2006 Nov 15;16(22):5748-51. doi: 10.1016/j.bmcl.2006.08.086.
Jason M Elliott  1 ,  Robert W Carling ,  Mark Chambers ,  Gary G Chicchi ,  Peter H Hutson ,  A Brian Jones ,  Angus MacLeod ,  Rose Marwood ,  Georgina Meneses-Lorente ,  Elena Mezzogori ,  Fraser Murray ,  Michael Rigby ,  Inmaculada Royo ,  Michael G N Russell ,  Bindi Sohal ,  Kwei Lan Tsao ,  Brian Williams
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. [email protected]
PMID: 16950620 DOI: 10.1016/j.bmcl.2006.08.086
Abstract

A new class of potent NK3R antagonists based on the N',2-diphenylquinoline-4-carbohydrazide core is described. In an ex vivo assay in gerbil, the lead compound 2g occupies receptors within the CNS following oral dosing (Occ(90) 30 mg/kg po; plasma Occ(90) 0.95 microM) and has good selectivity and promising PK properties.