1 research outputs found
Design and Synthesis of 4‑Heteroaryl 1,2,3,4-Tetrahydroisoquinolines as Triple Reuptake Inhibitors
A series of 4-bicyclic heteroaryl
1,2,3,4-tetrahydroisoquinoline
inhibitors of the serotonin transporter (SERT), norepinephrine transporter
(NET), and dopamine transporter (DAT) was discovered. The synthesis
and structure–activity relationship (SAR) of these triple reuptake
inhibitors (TRIs) will be discussed. Compound <b>10i</b> (AMR-2),
a very potent inhibitor of SERT, NET, and DAT, showed efficacy in
the rat forced-swim and mouse tail suspension models with minimum
effective doses of 0.3 and 1 mg/kg (<i>po</i>), respectively.
At efficacious doses in these assays, <b>10i</b> exhibited substantial
occupancy levels at the three transporters in both rat and mouse brain.
The study of the metabolism of <b>10i</b> revealed the formation
of a significant active metabolite, compound <b>13</b>