Structure-activity relationships of the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ol series of monoamine reuptake inhibitors.

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Mahaney PE, Kim CY, Coghlan RD, Cohn ST, Heffernan GD, Huselton CA, Terefenko EA, Vu AT, Zhang P, Burroughs KD, Cosmi SA, Bray JA, Johnston GH, Deecher DC, Trybulski EJ

Structure-activity relationships of the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ol series of monoamine reuptake inhibitors.

Bioorg Med Chem Lett. 2009 Oct 1;19(19):5807-10. doi: 10.1016/j.bmcl.2009.07.050. Epub 2009 Aug 25.

PubMed ID

19713106 [ View in PubMed

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Abstract

The SAR of a series of 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols as monoamine reuptake inhibitors, with a goal to improve both potency toward inhibiting the norepinephrine transporter and selectivity over the serotonin transporter, is reported. The effect of specific substitution on both the 3-phenyl group and the indole moiety were explored. This study led to the discovery of compound 20 which inhibited the norepinephrine transporter with an IC50 value of 4 nM while exhibiting 86-fold selectivity over the serotonin transporter.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Desipramine	Sodium-dependent noradrenaline transporter	IC 50 (nM)	3.4	N/A	N/A	Details
Fluoxetine	Sodium-dependent serotonin transporter	IC 50 (nM)	9.4	N/A	N/A	Details