Synthesis and structure-activity relationships of new arylpiperazines: para substitution with electron-withdrawing groups decrease binding to 5-HT(1A) and D(2A) receptors.
Compounds in which N-phenylpiperazines were linked by a propyloxy chain to position 6 or 7 of a coumarin ring were designed and synthesised, and their affinities for 5-HT(1A) and D(2A) receptors were determined by radioligand binding assays. The influence of para substitution in the phenyl ring, substitution at position 4 of the coumarin system, and the coumarin position at which the piperazinylalkyl chain is linked was explored. Electron-withdrawing phenyl ring substituents para to the piperazine strongly reduced activity at both receptors. Binding at 5HT(1A) was influenced by the bulk of substituents at position 4 of the coumarin system, and binding at D(2A) by their electronic properties. Neither binding affinity was significantly affected by whether the piperazinylalkyl chain was inserted at position 6 or 7 of the coumarin system.
Department of Organic Chemistry, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain. qolsant@usc.es
Lourdes
L
Santana
Eugenio
E
Uriarte
Yagamare
Y
Fall
Marta
M
Teijeira
Carmen
C
Terán
Emilia
E
García-Martínez
Bo-Ragnar
BR
Tolf
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry; D015195:Drug Design; D004583:Electrons; D005347:Fibroblasts; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D020891:Raclopride / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D013329:Structure-Activity Relationship
D003374:Coumarins; D007202:Indicators and Reagents; D010879:Piperazines; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D020891:Raclopride; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin