Synthesis of new hexahydro- and octahydropyrido[1,2-c]pyrimidine derivatives with an arylpiperazine moiety as ligands for 5-HT1A and 5-HT2A receptors.

Synthesis applied to prepare compounds 5-15 and 17-22 discussed in this paper has been presented in Scheme 1. Multi-stage preparation techniques were used to obtain 4-aryl-hexahydro 1-4 and (R,R) and (S,S) 4-aryl-octahydropyrido[1,2-c]pyrimidine-1,3-dione (16) derivatives, being the starting compounds for further modification. N-Alkylation of the imide group in compounds 1-4 and 16 followed, using 1,4-dibromobutane to yield monobromobutyl derivatives 5-8 and 17. Subsequent condensation of those compounds with appropriate 1-aryl or 1-heteroarylpiperazine led to the final hexahydro- 9-15 and octahydro- 18-22 pyrido[1,2-c]pyrimidine-1,3-dione derivatives. The final products were subjected to screening test to elucidate the affinity to 5-HT1A and 5-HT2A receptors.