Synthesis of new 4-heteroaryl-2-phenylquinolines and their pharmacological activity as NK-2/NK-3 receptor ligands

Arch Pharm (Weinheim). 2007 Jan;340(1):17-25. doi: 10.1002/ardp.200600113.

Abstract

Substituted 4-heteroaryl-2-phenylquinolines were synthesized and tested on NK-2 and NK-3 receptors in order to get a better insight in the structure-activity relationship. On the whole, these molecules, which can be regarded as bioisosters of the NK-3 antagonist SB 218795, displayed a lower activity than the template. Ring electronic distribution and H-bond donor and acceptor positions played some role in selectivity, 2-imidazolyl substituted 2a showing affinity mainly towards NK-3 while 3-pyrazolyl substituted 4 displayed a preferential interaction with NK-2 receptor. Structural characterization of the synthesized compounds was achieved by NMR and mass techniques. Bidimensional 1H-NOESY experiments were a helpful tool for the assignment of the isomeric structures of compounds 9 and llb-c.

MeSH terms

  • Animals
  • Binding, Competitive
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Feasibility Studies
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Structure
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / metabolism
  • Quinolines / pharmacology
  • Receptors, Neurokinin-2 / genetics
  • Receptors, Neurokinin-2 / metabolism*
  • Receptors, Neurokinin-3 / genetics
  • Receptors, Neurokinin-3 / metabolism*
  • Structure-Activity Relationship
  • Transfection

Substances

  • Ligands
  • Quinolines
  • Receptors, Neurokinin-2
  • Receptors, Neurokinin-3
  • SB 218795