A series of new 1,2,4-benzothiadiazine derivatives with an arylpiperazine mojety linked at position 3 of the heterocyclic ringwere synthesized and assessed for their pharmacological profiles at a1-adrenoceptor subtypes (a1A, a1B and a1D) by functional experiments and by in vitro bindingstudies at human cloned 5-HT1A receptor. Compound 1 was identified as a novel a1D antagonist (pKba1D = 7.59; a1D/a1A > 389; a1D/a1B = 135) with high selectivity over 5-HT1A receptor (5-HT1A/a1D < 0.01), while compound 6, a 3,4-dihydro-derivative, was characterized as a novel 5-HT1A receptor ligand, highly selective over a1D-adrenoceptor subtype (pKi5-HT1A = 8.04; 5-HT1A/a1D = 1096). Further pharmacological studies demonstrated that 6 is a partial agonist at 5-HT1A receptor (Emax = 23, pD2 = 6.92).
1,2,4-Benzothiadiazine derivatives as alpha1 and 5-HT1A receptor ligands
BUCCIONI, Michela;MARUCCI, Gabriella;
2005-01-01
Abstract
A series of new 1,2,4-benzothiadiazine derivatives with an arylpiperazine mojety linked at position 3 of the heterocyclic ringwere synthesized and assessed for their pharmacological profiles at a1-adrenoceptor subtypes (a1A, a1B and a1D) by functional experiments and by in vitro bindingstudies at human cloned 5-HT1A receptor. Compound 1 was identified as a novel a1D antagonist (pKba1D = 7.59; a1D/a1A > 389; a1D/a1B = 135) with high selectivity over 5-HT1A receptor (5-HT1A/a1D < 0.01), while compound 6, a 3,4-dihydro-derivative, was characterized as a novel 5-HT1A receptor ligand, highly selective over a1D-adrenoceptor subtype (pKi5-HT1A = 8.04; 5-HT1A/a1D = 1096). Further pharmacological studies demonstrated that 6 is a partial agonist at 5-HT1A receptor (Emax = 23, pD2 = 6.92).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
