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ID: ALA4431349
Journal: Bioorg Med Chem Lett
Title: Synthesis and in vitro evaluation of water-soluble 1,4-diphenethylpiperazine analogs as novel inhibitors of the vesicular monoamine transporter-2.
Authors: Nickell JR, Culver JP, Janganati V, Zheng G, Dwoskin LP, Crooks PA.
Abstract: A small library of 1,4-diphenethylpiperazine analogs was synthesized and evaluated for inhibition of [(3)H]dihydrotetrabenazine binding and [(3)H]dopamine uptake at the vesicular monoamine transporter-2 (VMAT2). Results from these studies identified three novel molecules, 6b, 6e and 9a (Ki=35nM, 48nM and 37nM, respectively) that exhibit similar potency for inhibition of VMAT2 function compared with lobelane (Ki=45nM), and importantly, have enhanced water-solubility when compared to the previously reported 1,4-diphenethylpiperidine analogs. These 1,4-diphenethylpiperazine analogs constitute promising new leads in the discovery of potential pharmacotherapeutics for treatment of methamphetamine use disorders.
CiteXplore: 27524311