Pharmacophore-based discovery of 3,4-disubstituted pyrrolidines as a novel class of monoamine transporter inhibitors

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

Research output: Contribution to journalArticle

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Abstract

3,4-Disubstituted pyrrolidines were discovered as a novel class of monoamine transporter inhibitors through 3-D database pharmacophore searching using a new pharmacophore model. The most potent analogue 12 has Ki values of 0.084 μM in [3H]mazindol binding, 0.20, 0.23, and 0.031 μM in inhibition of dopamine (DA), serotonin (SER), and norepinephrine (NE) reuptake, respectively. Functional antagonism testing in vitro showed that 11 and 12 are weak cocaine antagonists.

Original languageEnglish (US)
Pages (from-to)1113-1118
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume11
Issue number9
DOIs
StatePublished - May 7 2001

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ASJC Scopus subject areas

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

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