Synthesis of 3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, displaying combined 5-HT uptake inhibiting and α2-adrenoceptor antagonistic activities:: A novel series of potential antidepressants

The synthesis of a series of novel 3-piperazinyimethyl-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles as novel dual 5-HT reuptake inhibitors and alpha(2)-adrenoceptor antagonists is described. Their affinity at the three different human alpha(2)-adrenoceptor subtypes and the 5-HT transporter site is reported. The in vivo activity of the compounds was measured in two different assays: (1) inhibition of pCA-induced excitation, which evaluates the ability to block the central 5-HT transporter, and (2) inhibition of xylazine-induced loss of righting, which evaluates the ability to block central alpha(2)-adrenoceptors. (C) 2003 Elsevier Ltd. All rights reserved.