Structure-activity relationships of norepinephrine reuptake inhibitors with benzothiadiazine dioxide or dihydrosulfostyril cores.
Basic Information
ID: ALA1155376
Journal: Bioorg Med Chem Lett
Title: Structure-activity relationships of norepinephrine reuptake inhibitors with benzothiadiazine dioxide or dihydrosulfostyril cores.
Authors: Fensome A, Goldberg J, McComas CC, Trybulski EJ, Woodworth RP, Deecher DC, Whiteside GT, Zhang P.
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.
CiteXplore: 20153188
DOI: 10.1016/j.bmcl.2010.01.056
Patent ID: ┄