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. Epub 2006 Sep 6.

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.

MeSH terms

  • Administration, Oral
  • Animals
  • CHO Cells
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Hydrazines / chemistry*
  • Hydrazines / pharmacology*
  • Neurotransmitter Agents / chemistry*
  • Neurotransmitter Agents / pharmacology*
  • Quinolines / chemistry*
  • Quinolines / pharmacology*
  • Receptors, Neurokinin-3 / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Hydrazines
  • N-((methoxycarbonyl)(phenyl)amino)-3-methoxy-2-phenylquinoline-4-carboxamide
  • Neurotransmitter Agents
  • Quinolines
  • Receptors, Neurokinin-3
  • carbohydrazide