Pharmacophore-based discovery of substituted pyridines as novel dopamine transporter inhibitors

Istvan J. Enyedy, Sukumar Sakamuri, Wahiduz A. Zaman, Kenneth M. Johnson, Shaomeng Wang

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


Abnormal dopamine signaling in brain has been implicated in several conditions such as cocaine abuse, Parkinson's disease and depression. Potent and selective dopamine transporter inhibitors may be useful as pharmacological tools and therapeutic agents. Simple substituted pyridines were discovered as novel dopamine transporter (DAT) inhibitors through pharmacophore-based 3D-database search. The most potent compound 18 has a Ki value of 79 nM in inhibition of WIN35,248 binding to dopamine transporter and 255 nM in inhibition of dopamine reuptake, respectively, as potent as cocaine. Preliminary structure-activity relationship studies show that the geometry and the nature of the substituents on the pyridine ring determine the inhibitory activity and selectivity toward the three monoamine transporters. The substituted pyridines described herein represent a class of novel DAT inhibitors with simple chemical structures and their discovery provides additional insights into the binding site of DAT.

Original languageEnglish (US)
Pages (from-to)513-517
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number3
StatePublished - Feb 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


Dive into the research topics of 'Pharmacophore-based discovery of substituted pyridines as novel dopamine transporter inhibitors'. Together they form a unique fingerprint.

Cite this