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

doi:10.1016/S0960-894X(01)00132-9

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 journal › Article › peer-review

45 Scopus citations

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 K_i 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 language	English (US)
Pages (from-to)	1113-1118
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	11
Issue number	9
DOIs	https://doi.org/10.1016/S0960-894X(01)00132-9
State	Published - May 7 2001
Externally published	Yes

ASJC Scopus subject areas

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

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10.1016/S0960-894X(01)00132-9

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

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.",

author = "Enyedy, {Istvan J.} and Zaman, {Wahiduz A.} and Sukumar Sakamuri and Kozikowski, {Alan P.} and Johnson, {Kenneth M.} and Shaomeng Wang",

note = "Funding Information: The financial support from the National Institute on Drug Abuse, National Institutes of Health (R01DA-11545) is highly appreciated.",

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T1 - Pharmacophore-based discovery of 3,4-disubstituted pyrrolidines as a novel class of monoamine transporter inhibitors

AU - Enyedy, Istvan J.

AU - Zaman, Wahiduz A.

AU - Sakamuri, Sukumar

AU - Kozikowski, Alan P.

AU - Johnson, Kenneth M.

AU - Wang, Shaomeng

N1 - Funding Information: The financial support from the National Institute on Drug Abuse, National Institutes of Health (R01DA-11545) is highly appreciated.

PY - 2001/5/7

Y1 - 2001/5/7

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AB - 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.

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

Abstract

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