(±)-2-(N-tert-Butylamino)-3'-[(125)I]-iodo-4'-azidopropiophenone: a dopamine transporter and nicotinic acetylcholine receptor photoaffinity ligand based on bupropion (Wellbutrin, Zyban)

Bioorg Med Chem Lett. 2012 Jan 1;22(1):523-6. doi: 10.1016/j.bmcl.2011.10.086. Epub 2011 Nov 4.


Towards addressing the knowledge gap of how bupropion interacts with the dopamine transporter (DAT) and nicotinic acetylcholine receptors (nAChRs), a ligand was synthesized in which the chlorine of bupropion was isosterically replaced with an iodine and a photoreactive azide was added to the 4'-position of the aromatic ring. Analog (±)-3 (SADU-3-72) demonstrated modest DAT and α4β2 nAChR affinity. A radioiodinated version was shown to bind covalently to hDAT expressed in cultured cells and affinity-purified, lipid-reincorporated human α4β2 neuronal nAChRs. Co-incubation of (±)-[(125)I]-3 with non-radioactive (±)-bupropion or (-)-cocaine blocked labeling of these proteins. Compound (±)-[(125)I]-3 represents the first successful example of a DAT and nAChR photoaffinity ligand based on the bupropion scaffold. Such ligands are expected to assist in mapping bupropion-binding pockets within plasma membrane monoamine transporters and ligand-gated nAChR ion channels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azides / chemical synthesis*
  • Azides / chemistry
  • Azides / pharmacology*
  • Bupropion / analogs & derivatives*
  • Bupropion / chemical synthesis
  • Bupropion / pharmacology*
  • Chemistry, Pharmaceutical / methods*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Drug Design
  • Humans
  • Iodine / chemistry
  • Iodine Radioisotopes / chemistry
  • Kinetics
  • Ligands
  • Models, Chemical
  • Photochemistry / methods
  • Receptors, Nicotinic / metabolism*


  • 2-(N-tert-butylamino)-3'-iodo-4'-azidopropiophenone
  • Azides
  • Dopamine Plasma Membrane Transport Proteins
  • Iodine Radioisotopes
  • Ligands
  • Receptors, Nicotinic
  • Bupropion
  • Iodine