New arylpiperazine derivatives with high affinity for alpha1A, D2 and 5-HT2A receptors

Bioorg Med Chem Lett. 2003 Jan 20;13(2):175-8. doi: 10.1016/s0960-894x(02)00933-2.

Abstract

A series of novel long-chain arylpiperazines bearing a coumarin fragment was synthesized and the compounds were evaluated for their affinity at alpha(1), D(2 )and 5-HT(2A) receptors. Most of the new compounds showed high affinity for the three types of receptors alpha(1A), D(2) and 5-HT(2A) which depends, fundamentally, on the substitution of the N(4) of the piperazine ring. From the series emerged compound 6, which had an haloperidol-like profile at D(2) and 5HT(2A) receptors (pK(i) values of 7.93 and 6.76 respectively). The higher alpha(1A) receptor affinity (pA(2)=9.07) of this compound could contribute to a more atypical antipsychotic profile than the haloperidol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Aorta, Thoracic / drug effects
  • Coumarins / chemistry
  • Dopamine Antagonists / pharmacology
  • Haloperidol / pharmacology
  • In Vitro Techniques
  • Indicators and Reagents
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Piperazines / chemical synthesis*
  • Piperazines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Adrenergic, alpha-1 / drug effects*
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Serotonin / drug effects*
  • Structure-Activity Relationship

Substances

  • Coumarins
  • Dopamine Antagonists
  • Indicators and Reagents
  • Piperazines
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Adrenergic, alpha-1
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Haloperidol