Synthesis and 5-HT1A/5-HT2A receptor activity of new N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclohexanepyrrolidine-2,5-dione and 3-spiro-beta-tetralonepyrrolidine-2,5-dione.

Novel N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclo-hexanepyrrolidine-2,5-dione (5-7) and 3-spiro-beta-tetralonepyrrolidine-2,5-dione (8-10) were synthesized and their 5-HT1A and 5-HT2A receptor affinities were determined. All tested compounds exhibited moderate to low 5-HT1A receptor affinity, whereas compounds 5-7 demonstrated high 5-HT2A receptor affinity (Ki = 27, 46 and 15 nM, respectively) and features of 5-HT2A receptor antagonists. Introduction of a beta-tetralone fragment in the 3-position of pyrrolidine-2,5-dione ring (8-10) did not affect 5-HT1A but decreased 5-HT2A receptor affinity.