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

Farmaco. 2002 Dec;57(12):959-71. doi: 10.1016/s0014-827x(02)01274-0.

Abstract

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.

MeSH terms

  • Animals
  • Binding, Competitive
  • Cerebral Cortex / metabolism
  • In Vitro Techniques
  • Ligands
  • Piperazines / chemical synthesis*
  • Piperazines / metabolism
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / metabolism
  • Radioligand Assay
  • Rats
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Antagonists / metabolism

Substances

  • Ligands
  • Piperazines
  • Pyrimidines
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Adrenergic, alpha-1
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists