Synthesis and receptor binding studies of 3-substituted piperazine derivatives.
In order to find novel receptor ligands various substituents were introduced into the side chain in position 3 of the piperazine 5. During nucleophilic substitution of the hydroxy group of 5 aziridinium ions were formed, resulting in rearranged 1,4-diazepanes and piperazines as side products. 1,2-anellated piperazines 15, 18 and 19 were prepared by hydrogenation of the alpha,beta-unsaturated ester 13 and by condensation of the primary amine 16b with formaldehyde, respectively. Receptor binding studies with radioligands revealed that the phenylacetamide 17b interacts with moderate affinity (K(i) = 181 nM) and considerable selectivity with sigma(1) receptors.
Bedürftig
Stephan
S
Institut für Pharmazeutische und Medizinische Chemie, Münster, Germany.
Wünsch
Bernhard
B
D000818:Animals; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D008024:Ligands; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D011957:Receptors, Opioid / Q000819:agonists* / Q000737:chemistry; D017480:Receptors, sigma / Q000819:agonists / Q000737:chemistry; D000097605:Sigma-1 Receptor
D008024:Ligands; D010879:Piperazines; D011957:Receptors, Opioid; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor