New arylpiperazine derivatives with high affinity for alpha1A, D2 and 5-HT2A receptors.
A series of novel long-chain arylpiperazines bearing a coumarin fragment was synthesized and the compounds were evaluated for their affinity at alpha(1), D(2 )and 5-HT(2A) receptors. Most of the new compounds showed high affinity for the three types of receptors alpha(1A), D(2) and 5-HT(2A) which depends, fundamentally, on the substitution of the N(4) of the piperazine ring. From the series emerged compound 6, which had an haloperidol-like profile at D(2) and 5HT(2A) receptors (pK(i) values of 7.93 and 6.76 respectively). The higher alpha(1A) receptor affinity (pA(2)=9.07) of this compound could contribute to a more atypical antipsychotic profile than the haloperidol.
González-Gómez
J C
JC
Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago, Campus Sur s/n, E-15782 Santiago de Compostela, Spain. qolsant@usc.es
Santana
L
L
Uriarte
E
E
Brea
J
J
Villazón
M
M
Loza
M I
MI
De Luca
M
M
Rivas
M E
ME
Montenegro
G Y
GY
Fontenla
J A
JA
D000465:Algorithms; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D013329:Structure-Activity Relationship
D003374:Coumarins; D018492:Dopamine Antagonists; D007202:Indicators and Reagents; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D018340:Receptors, Adrenergic, alpha-1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D006220:Haloperidol