Structure-activity relationships of norepinephrine reuptake inhibitors with benzothiadiazine dioxide or dihydrosulfostyril cores.

Article Details

Citation

Copy to clipboard

Fensome A, Goldberg J, McComas CC, Trybulski EJ, Woodworth RP, Deecher DC, Whiteside GT, Zhang P

Structure-activity relationships of norepinephrine reuptake inhibitors with benzothiadiazine dioxide or dihydrosulfostyril cores.

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1555-8. doi: 10.1016/j.bmcl.2010.01.056. Epub 2010 Jan 20.

PubMed ID

20153188 [ View in PubMed

]

Abstract

Two related series of selective norepinephrine reuptake inhibitors were synthesized based on 3,4-dihydro-1H-2,1,3-benzothiadiazine 2,2-dioxide or 3,4-dihydrosulfostyril cores, and screened for monoamine reuptake inhibition. Structure-activity relationships were determined for the series' in vitro potency and selectivity versus serotonin or dopamine transporter inhibition, and analogs based on both cores were identified as potent and selective NRIs. The 3,4-dihydrosulfostyril series was further tested for microsome stability, and compound 16j, which was optimized for both potency and stability, showed efficacy in an in vivo model of thermoregulatory dysfunction.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Atomoxetine	Sodium-dependent noradrenaline transporter	IC 50 (nM)	3	N/A	N/A	Details