866208-22-2Relevant academic research and scientific papers
1-(Indolin-1-yl)-1-phenyl-3-propan-2-olamines as potent and selective norepinephrine reuptake inhibitors
Vu, An T.,Cohn, Stephen T.,Zhang, Puwen,Kim, Callain Y.,Mahaney, Paige E.,Bray, Jenifer A.,Johnston, Grace H.,Koury, Elizabeth J.,Cosmi, Scott A.,Deecher, Darlene C.,Smith, Valerie A.,Harrison, James E.,Leventhal, Liza,Whiteside, Garth T.,Kennedy, Jeffrey D.,Trybulski, Eugene J.
experimental part, p. 2051 - 2062 (2010/08/22)
Efforts to identify new selective and potent norepinephrine reuptake inhibitors (NRIs) for multiple indications by structural modification of the previous 3-(arylamino)-3-phenylpropan-2-olamine scaffold led to the discovery of a novel series of 1-(indolin-1-yl)-1-phenyl-3-propan-2-olamines (9). Investigation of the structure-activity relationships revealed that small alkyl substitution at the C3 position of the indoline ring enhanced selectivity for the norepinephrine transporter (NET) over the serotonin transporter (SERT). Several compounds bearing a 3, 3-dimethyl group on the indoline ring, 9k, 9o,p, and 9s,t, exhibited potent inhibition of NET (IC50= 2.7-6.5 nM) and excellent selectivity over both serotonin and dopamine transporters. The best example from this series, 9p, a potent and highly selective NRI, displayed oral efficacy in a telemetric rat model of ovariectomized-induced thermoregulatory dysfunction, a mouse p-phenylquinone (PPQ) model of acute visceral pain, and a rat spinal nerve ligation (SNL) model of neuropathic pain.
