Functional characteristics of a series of N4-substituted 1-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazines as 5-HT1A receptor ligands. Structure-activity relationships.
The agonistic/antagonistic profile of a series of 10 N4-substituted 1-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazines is evaluated in the in vitro adenylyl cyclase assay. The profile is severely affected by the characteristics of the N4-substituents ranging from full agonism (benzamidoethyl derivative 1), mixed agonism/antagonism (phthalimidobutyl derivative 7) to predominantly antagonism (saccharinbutyl derivate 9). A novel full antagonist 10, as potent as WAY 100635, is obtained by substitution of Cl at C-7 of the benzodioxinyl moiety in 9.
van Steen
B J
BJ
Solvay Pharmaceuticals Research Laboratories, Weesp, The Netherlands.
van Wijngaarden
I
I
Ronken
E
E
Soudijn
W
W
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000378:metabolism; D013329:Structure-Activity Relationship
D008024:Ligands; D010879:Piperazines; D011725:Pyridines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C056895:flesinoxan; C063828:eltoprazine; C043077:ipsapirone; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000262:Adenylyl Cyclases