Synthesis and structure-activity relationships of a new model of arylpiperazines. 3.1 2-[omega-(4-arylpiperazin-1-yl)alkyl]perhydropyrrolo- [1,2-c]imidazoles and -perhydroimidazo[1,5-a]pyridines: study of the influence of the terminal amide fragment on 5-HT1A affinity/selectivity.
A series of new arylpiperazine derivatives 2, which are devoid of the terminal amide fragment present in related 5-HT1A ligands, was prepared and evaluated for affinity at 5-HT1A and alpha 1 receptors. All the compounds 2 demonstrated high affinity for the 5-HT1A receptor and moderate affinity for alpha 1 receptor binding sites. Structure-activity relationship (SAR) studies suggest that there is influence of electronic factors on the no-pharmacophoric part of the alpha 1 receptor site. However there is no influence of electronic interactions on the stabilization of the 5-HT1A receptor-ligand complex.
López-Rodríguez
M L
ML
Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense, Madrid, Spain. mluzlr@eucmax.sim.ucm.es
Morcillo
M J
MJ
Fernández
E
E
Porras
E
E
Murcia
M
M
Sanz
A M
AM
Orensanz
L
L
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D066298:In Vitro Techniques; D008956:Models, Chemical; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000378:metabolism; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011224:Prazosin