Derivatives of (3S)-N-(biphenyl-2-ylmethyl)pyrrolidin-3-amine as selective noradrenaline reuptake inhibitors: Reducing P-gp mediated efflux by modulation of H-bond acceptor capacity
Derivatives of (3S)-N-(biphenyl-2-ylmethyl)pyrrolidin-3-amine are disclosed as a new series of noradrenaline reuptake inhibitors (NRI). Carboxamide 9e, carbamate 11b and sulfonamide 13a were identified as potent NRIs with excellent selectivity over SRI and DRI, good in vitro metabolic stability and weak CYP inhibition. Carbamate 11b demonstrated superior transit performance in MDCK-mdr1 cell lines with minimal P-gp efflux which was attributed to reduced HBA capacity of the carbamate group. Evaluation in vivo, in rat microdialysis experiments, showed 11b increased noradrenaline levels by 400% confirming good CNS penetration.
Fish, Paul V.,Barta, Nancy S.,Gray, David L.F.,Ryckmans, Thomas,Stobie, Alan,Wakenhut, Florian,Whitlock, Gavin A.
scheme or table
p. 4355 - 4359
(2009/04/06)
3-AMINOPYRROLIDINES AS INHIBITORS OF MONOAMINE UPTAKE
The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, which are useful for the inhibition of the uptake of one or more physiologically active monoamines (serotonin, norepinephrine, and dopamine).
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Page/Page column 63
(2008/06/13)
TREATMENT OF LEARNING DISABILITIES AND MOTOR SKILLS DISORDER WITH NOREPINEPHRINE REUPTAKE INHIBITORS
Provided are methods and medicaments for treating a learning disability or a Motor Skills Disorder, comprising administering to a patient in need of such treatment an effective amount of a selective norepinephrine reuptake inhibitor.
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Page/Page column 223
(2010/02/11)
TREATMENT OF PERVASIVE DEVELOPMENTAL DISORDERS WITH NOREPINEPHRINE REUPTAKE INHIBITORS
Provided are methods and medicaments for treating a Pervasive Developmental Disorder, comprising administering to a patient in need of such treatment an effective amount of a selective norepinephrine reuptake inhibitor.
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Page/Page column 226
(2010/02/11)
TREATMENT OF HOT FLASHES, IMPULSE CONTROL DISORDERS AND PERSONALITY CHANGE DUE TO A GENERAL MEDICAL CONDITION
Selective norepinephrine reuptake inhibitors are useful for the prevention or treatment of hot flashes, vasomotor symptoms, impulse control disorders or personality change due to a general medical condition.
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Page/Page column 225
(2010/02/12)
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