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 microM in [3H]mazindol binding, 0.20, 0.23, and 0.031 microM 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.
authors.affiliation: Department of Oncology, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: I J
authors.initials: IJ
authors.lastname: Enyedy
authors.forename: W A
authors.initials: WA
authors.lastname: Zaman
authors.forename: S
authors.initials: S
authors.lastname: Sakamuri
authors.forename: A P
authors.initials: AP
authors.lastname: Kozikowski
authors.forename: K M
authors.initials: KM
authors.lastname: Johnson
authors.forename: S
authors.initials: S
authors.lastname: Wang
mesh_terms: D015306:Biogenic Monoamines / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D003042:Cocaine / Q000037:antagonists & inhibitors; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors / Q000378:metabolism; D008454:Mazindol / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D015306:Biogenic Monoamines; D002352:Carrier Proteins; D018765:Dopamine Uptake Inhibitors; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D008454:Mazindol; D003042:Cocaine