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.
Herold
Franciszek
F
Department of Drug Technology, Faculty of Pharmacy, The Medical University of Warsaw, Banacha 1, 02-970 Warsaw, Poland.
Kleps
Jerzy
J
Wolska
Irena
I
Nowak
Gabriel
G
D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000378:metabolism
D008024:Ligands; D010879:Piperazines; D011743:Pyrimidines; D044402:Receptor, Serotonin, 5-HT2A; D018340:Receptors, Adrenergic, alpha-1; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists