Bivalent ligand approach on 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine: synthesis and binding affinities for 5-HT(7) and 5-HT(1A) receptors.
We here report on the synthesis and binding properties at 5-HT(7) and 5-HT(1A) receptors of ligands 3-12, that were designed according to the 'bivalent ligand' approach. Two moieties of the 5-HT(7)/5-HT(1A) ligand 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine (1) were linked through their 3-methoxy substituent by polymethylene chains of variable length, with the aim to increase the affinity for 5-HT(7) receptor and the selectivity over 5-HT(1A) receptors. In the best cases, the dimers showed affinities for 5-HT(7) receptors as high as the monomer with no improvement in selectivity. Some dimers displayed 5-HT(1A) receptor affinities slightly higher than monomer 1.
Leopoldo
Marcello
M
Università degli Studi di Bari, Dipartimento Farmaco-Chimico, via Orabona, 4, Bari, Italy. leopoldo@farmchim.uniba.it
Lacivita
Enza
E
Colabufo
Nicola A
NA
Niso
Mauro
M
Berardi
Francesco
F
Perrone
Roberto
R
D000818:Animals; D002460:Cell Line; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry*; D011485:Protein Binding; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship
C522379:4-(2-(3-methoxyphenyl)ethyl)-1-(2-methoxyphenyl)piperazine; C522380:5-HT(7) receptor, rat; D008024:Ligands; D010879:Piperazines; D011985:Receptors, Serotonin; D044282:Receptor, Serotonin, 5-HT1A