866211-61-2Relevant academic research and scientific papers
1- Or 3-(3-amino-2-hydroxy-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2- ones: Potent, selective, and orally efficacious norepinephrine reuptake inhibitors
Zhang, Puwen,Terefenko, Eugene A.,Bray, Jenifer,Deecher, Darlene,Fensome, Andrew,Harrison, Jim,Kim, Callain,Koury, Elizabeth,Mark, Lilly,McComas, Casey C.,Mugford, Cheryl A.,Trybulski, Eugene J.,Vu, An T.,Whiteside, Garth T.,Mahaney, Paige E.
experimental part, p. 5703 - 5711 (2010/02/28)
Sequential structural modifications of the aryloxypropanamine template (e.g., atomoxetine, 2) led to a novel series of 1-(3-amino-2-hydroxy-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors (NRIs). In general, this series of compounds potently blocked the human norepinephrine transporter (hNET) while exhibiting selectivity at hNET against both the human serotonin (hSERT) and dopamine transporters (hDAT). Numerous compounds (e.g., 19-22) had low nonamolar hNET potency with IC 50 values of 7-10 nM and excellent selectivity (>500 fold) at hNET over hSERT and hDAT. Several compounds, such as 20 and 22, were tested in a telemetric rat model of ovariectomized-induced thermoregulatory dysfunction and were efficacious at oral doses of 3 mg/kg in reducing the tail skin temperature. In addition, compound 20 was also studied in the rat hot plate and spinal nerve ligation (SNL) models of acute and neuropathic pain, respectively, and was orally efficacious at doses of 3-10 mg/kg.
Synthesis and activity of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors
Zhang, Puwen,Terefenko, Eugene A.,McComas, Casey C.,Mahaney, Paige E.,Vu, An,Trybulski, Eugene,Koury, Elizabeth,Johnston, Grace,Bray, Jenifer,Deecher, Darlene
scheme or table, p. 6067 - 6070 (2009/08/07)
A series of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors was discovered. Several compounds such as 15 and 20 showed good hNET potency. Compounds 15 and 20 also displayed excellent selectivity at hNET that appeared superior to those of reboxetine and atomoxetine (4 and 5).
Phenylaminopropanol derivatives and methods of their use
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Page/Page column 93, (2008/06/13)
The present invention is directed to phenylaminopropanol derivatives of formula I: or a pharmaceutically acceptable salt thereof, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof.
