Synthesis and 5-HT2A, 5-HT1A and alpha1-binding affinities of 2-[2-Hydroxy-3-(pyridin-3-yl-methyl)amino]-, 2-[2-hydroxy-3-(2-pyridin-2-yl-ethyl)amino]- and 2-[2-hydroxy-3-(4-N-methyl-piperazin-1-yl)-amino]propoxybenzaldehyde-O-(substituted) benzyl oximes.
Some oxime ether-substituted aryloxypropanolamines 3-5, structurally related to the active metabolite 2 of sarpogrelate 1, were synthesized and tested for their affinities at 5-HT2A and 5-HT1A serotoninergic receptors as well as at the alpha1-adrenoceptor. The results show that the compounds possess, at least partially, the ability of the model compounds 1 and 2 to interact with the 5-HT2A-receptors; they have the same selectivity towards 5-HT2A receptors vs alpha1-adrenoceptors.
Orlandini
Elisabetta
E
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Pisa, Italy. eorlandini@farm.unipi.it
Rapposelli
Simona
S
Nencetti
Susanna
S
Giannaccini
Gino
G
Betti
Laura
L
Balsamo
Aldo
A
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D066298:In Vitro Techniques; D007650:Ketanserin / Q000378:metabolism; D008024:Ligands; D015394:Molecular Structure; D010091:Oximes / Q000138:chemical synthesis / Q000378:metabolism*; D010879:Piperazines / Q000138:chemical synthesis / Q000378:metabolism*; D011224:Prazosin / Q000378:metabolism; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis / Q000378:metabolism*; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000378:metabolism; D013329:Structure-Activity Relationship; D013386:Succinates / Q000138:chemical synthesis / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D008024:Ligands; D010091:Oximes; D010879:Piperazines; D011725:Pyridines; D044402:Receptor, Serotonin, 5-HT2A; D018340:Receptors, Adrenergic, alpha-1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013386:Succinates; D044282:Receptor, Serotonin, 5-HT1A; C064294:sarpogrelate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D011224:Prazosin