Synthesis of new 4-butyl-arylpiperazine-3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives and evaluation for their 5-HT1A and D2 receptor affinity and serotonin transporter inhibition

Abstract

A series of novel 4-butyl-arylpiperazine-3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives were synthesized and evaluated for their 5-HT_1A/D₂ receptor affinity and serotonin reuptake inhibition. The compounds exhibited high affinity for the 5-HT_1A receptor, (especially 4dK_i = 0.4 nM) which depended on the substitution pattern at the phenylpiperazine moiety. From this series screen, compound 4c emerged with promising mixed receptor profiles for the 5-HT_1A/D₂ receptors and the serotonin transporter (K_i = 1.3 nM, 182 nM and 64 nM, respectively).