Synthesis and pharmacology of isoquinuclidine derivatives as 5-HT(3) ligands.
A series of 4-amino-5-chloro-2-methoxybenzoates and benzamides containing the 5- and 6-isoquinuclidinyl system was synthesised and evaluated for binding to 5-HT(3), 5-HT(4) and D(2) receptors. In general, the isoquinuclidine derivatives at the 5-position have shown to be more potent as 5-HT(3) ligands but they also possess 5-HT(4) and D(2) properties. However, the results show that the derivatives at the 6-position afforded the most promising compounds in terms of both receptor affinity and selectivity.
Iriepa
Isabel
I
Departamento de Química Orgánica, Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33,600, 28871 Alcalá de Henares, Madrid, Spain. isabel.iriepa@uah.es
Villasante
Francisco J
FJ
Gálvez
Enrique
E
Labeaga
Luis
L
Innerarity
Ana
A
Orjales
Aurelio
A
D008024:Ligands; D011812:Quinuclidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D013237:Stereoisomerism
D008024:Ligands; D011812:Quinuclidines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3