Syntheses and binding affinities of 6-nitroquipazine analogues for serotonin transporter. Part 2: 4-substituted 6-nitroquipazines

Bioorg Med Chem Lett. 2002 Mar 11;12(5):811-5. doi: 10.1016/s0960-894x(02)00028-8.

Abstract

Eleven 4-substituted derivatives of 6-nitroquipazine were synthesized and evaluated for their abilities to displace [3H]citalopram binding to the rat cortical synaptic membranes. Among them, 4-chloro-6-nitroquipazine was shown to possess the highest binding affinity (K(i=)0.03 nM) which was approximately 6 times higher than that of 6-nitroquipazine (K(i)=0.17 nM) itself. In this paper, we describe the syntheses of 4-substituted 6-nitroquipazine derivatives, the results of corresponding biological evaluation and the SAR study.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Carrier Proteins / metabolism*
  • Cerebral Cortex / metabolism
  • Citalopram / pharmacokinetics
  • Drug Design
  • Fluoxetine / pharmacology
  • Inhibitory Concentration 50
  • Kinetics
  • Male
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins*
  • Models, Structural
  • Nerve Tissue Proteins*
  • Paroxetine / pharmacology
  • Quipazine / analogs & derivatives*
  • Quipazine / chemical synthesis*
  • Quipazine / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Antagonists / metabolism*
  • Serotonin Plasma Membrane Transport Proteins
  • Structure-Activity Relationship

Substances

  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Serotonin Antagonists
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, rat
  • Fluoxetine
  • Citalopram
  • Paroxetine
  • Quipazine
  • 6-nitroquipazine