A structure-affinity relationship study on derivatives of N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide, a high-affinity and selective D(4) receptor ligand

J Med Chem. 2000 Jan 27;43(2):270-7. doi: 10.1021/jm991138z.

Abstract

N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (1), a high-affinity and selective dopamine D(4) receptor ligand, was chosen as a lead, and structural modifications were done on its amide bond and on its alkyl chain linking the benzamide moiety to the piperazine ring and by preparing some semirigid analogues. The binding profile at dopamine D(4) and dopamine D(2), serotonin 5-HT(1A), and adrenergic alpha(1) receptors of 16 new compounds was determined. From the results emerged that the modification of the amide bond and the elongation of the intermediate alkyl chain caused a decrease in dopamine D(4) receptor affinity. All prepared semirigid analogues displayed D(4) receptor affinity values in the same range of the opened counterparts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / chemistry*
  • Benzamides / metabolism
  • Benzamides / pharmacology
  • Dopamine Agents / chemistry*
  • Dopamine Agents / metabolism
  • Dopamine Agents / pharmacology
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Piperazines / chemistry*
  • Piperazines / metabolism
  • Piperazines / pharmacology
  • Rats
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D4
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin, 5-HT1
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Benzamides
  • DRD4 protein, human
  • Dopamine Agents
  • Drd4 protein, rat
  • Ligands
  • N-(2-(4-(4-chlorophenyl)piperazin-1-yl)ethyl)-3-methoxybenzamide
  • Piperazines
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Recombinant Proteins
  • Receptors, Dopamine D4