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

42 Citations (Scopus)

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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Pyrrolidines
Mazindol
Cocaine
Dopamine
Serotonin
Norepinephrine
Databases
Testing
In Vitro Techniques

ASJC Scopus subject areas

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

Cite this

Pharmacophore-based discovery of 3,4-disubstituted pyrrolidines as a novel class of monoamine transporter inhibitors. / Enyedy, Istvan J.; Zaman, Wahiduz A.; Sakamuri, Sukumar; Kozikowski, Alan P.; Johnson, Kenneth M.; Wang, Shaomeng.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 11, No. 9, 07.05.2001, p. 1113-1118.

Research output: Contribution to journalArticle

Enyedy, Istvan J. ; Zaman, Wahiduz A. ; Sakamuri, Sukumar ; Kozikowski, Alan P. ; Johnson, Kenneth M. ; Wang, Shaomeng. / Pharmacophore-based discovery of 3,4-disubstituted pyrrolidines as a novel class of monoamine transporter inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2001 ; Vol. 11, No. 9. pp. 1113-1118.
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