Discovery of substituted 3,4-diphenyl-thiazoles as a novel class of monoamine transporter inhibitors through 3-D pharmacophore search using a new pharmacophore model derived from mazindol

Bioorg Med Chem Lett. 2002 Jul 8;12(13):1775-8. doi: 10.1016/s0960-894x(02)00243-3.

Abstract

Substituted 3,4-diphenyl-1,3-thiazols were identified as a class of novel and potent monoamine transporter inhibitors through a 3-D pharmacophore search using a new pharmacophore model derived from mazindol. The most potent compound (13) has K(i) values of 24 and 23 nM in binding to dopamine transporter and inhibition of dopamine reuptake, respectively.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Biphenyl Compounds / chemical synthesis
  • Biphenyl Compounds / chemistry*
  • Biphenyl Compounds / pharmacology
  • Cocaine / analogs & derivatives*
  • Cocaine / metabolism
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors / chemical synthesis
  • Dopamine Uptake Inhibitors / chemistry*
  • Dopamine Uptake Inhibitors / pharmacology
  • Ligands
  • Mazindol / chemistry*
  • Mazindol / pharmacology
  • Membrane Glycoproteins*
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / metabolism
  • Models, Molecular
  • Nerve Tissue Proteins*
  • Norepinephrine / metabolism
  • Serotonin / metabolism
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry*
  • Thiazoles / pharmacology

Substances

  • Biphenyl Compounds
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors
  • Ligands
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Thiazoles
  • Serotonin
  • (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester
  • Mazindol
  • Cocaine
  • Dopamine
  • Norepinephrine