biostudies-literatureOstrowska KMedical University of Warsaw, Faculty of Pharmacy2779https://www.ebi.ac.uk/biostudies/studies/S-EPMC9917830biostudies-literatureUnknown24(3)A series of 15 new derivatives of 6-acetyl-7-hydroxy-4-methylcoumarin containing a piperazine group were designed with the help of computational methods and were synthesized to study their affinity for the serotonin 5-HT_1A and 5-HT_2A receptors. Among them, 6-acetyl-7-{4-[4-(3-bromophenyl)piperazin-1-yl]butoxy}-4-methylchromen-2-one (<b>4</b>) and 6-acetyl-7-{4-[4-(2-chlorophenyl)piperazin-1-yl]butoxy}-4-methylchromen-2-one (<b>7</b>) exhibited excellent activity for 5-HT_1A receptors with Ki values 0.78 (0.4-1.4) nM and 0.57 (0.2-1.3) nM, respectively, comparable to the Ki values of 8-OH-DPAT (0.25 (0.097-0.66) nM). The equilibrium dissociation constant values of the tested compounds showed differential intrinsic activities of the agonist and antagonist modes.International journal of molecular sciencesNew Piperazine Derivatives of 6-Acetyl-7-hydroxy-4-methylcoumarin as 5-HT_1A Receptor Agents.PMC9917830FW24/2/F/GW/N/20FW24/F/PW2/N/20Bujalska-Zadrozny MDobrzycki LGryczka WOstrowska KLesniak ATrzaskowski BfalseNew Piperazine Derivatives of 6-Acetyl-7-hydroxy-4-methylcoumarin as 5-HT_1A Receptor Agents.A series of 15 new derivatives of 6-acetyl-7-hydroxy-4-methylcoumarin containing a piperazine group were designed with the help of computational methods and were synthesized to study their affinity for the serotonin 5-HT_1A and 5-HT_2A receptors. Among them, 6-acetyl-7-{4-[4-(3-bromophenyl)piperazin-1-yl]butoxy}-4-methylchromen-2-one (<b>4</b>) and 6-acetyl-7-{4-[4-(2-chlorophenyl)piperazin-1-yl]butoxy}-4-methylchromen-2-one (<b>7</b>) exhibited excellent activity for 5-HT_1A receptors with Ki values 0.78 (0.4-1.4) nM and 0.57 (0.2-1.3) nM, respectively, comparable to the Ki values of 8-OH-DPAT (0.25 (0.097-0.66) nM). The equilibrium dissociation constant values of the tested compounds showed differential intrinsic activities of the agonist and antagonist modes.2023-01-01T00:00:00Z2023 Feb2026-04-08T14:15:01.195Z2025-02-19T02:23:59.774ZS-EPMC99178303676911710.3390/ijms24032779