Synthesis and in vitro binding studies of piperazine-alkyl-naphthamides: impact of homology and sulphonamide/carboxamide bioisosteric replacement on the affinity for 5-HT1A, alpha2A, D4.2, D3 and D2L receptors

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5199-202. doi: 10.1016/j.bmcl.2010.07.002. Epub 2010 Jul 6.

Abstract

A series of carboxamide and sulphonamide alkyl(ethyl to hexyl)piperazine analogues were prepared and tested for their affinity to bind to a range of receptors potentially involved in psychiatric disorders. These chemical modifications led us to explore the impact of homology and bioisosteric replacement of the amide group. All of these compounds possessed a high affinity for 5-HT(1A) receptors, irrespective of the size of the linker, the carboxamide derivative with a pentyl linker had the highest affinity for alpha(2A) receptor sites and also a high affinity for 5-HT(1A) and D3 receptors. The sulphonamide analogue with a hexyl linker possessed a high affinity for 5-HT(1A), D4.2 and D3 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Carboxylic Acids / chemistry
  • In Vitro Techniques
  • Naphthalenes / chemistry
  • Naphthalenes / metabolism*
  • Piperazines / chemistry*
  • Receptors, Dopamine / metabolism*
  • Receptors, Serotonin / metabolism*
  • Sulfonamides / chemistry*

Substances

  • Amides
  • Carboxylic Acids
  • Naphthalenes
  • Piperazines
  • Receptors, Dopamine
  • Receptors, Serotonin
  • Sulfonamides