The impact of spacer structure on 5-HT7 and 5-HT1A receptor affinity in the group of long-chain arylpiperazine ligands.
New cis-, trans-2-butene and 1,2-bismethylbenzene analogues of MM77 and NAN-190 (1-[4-[4-(2-methoxyphenyl)-piperazin-1-yl]-butyl]-pyrrolidine-2,5-dione and isoindole-1,3-dione, respectively) were synthesized. The differences in their in vitro affinity for serotonin 5-HT(7) and 5-HT(1A) receptors were explained using a conformational analysis. A bioactive conformation of those compounds for the 5-HT(7) receptor, different from that established for 5-HT(1A), was proposed.
Bojarski
Andrzej J
AJ
Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland. bojarski@if-pan.krakow.pl
Duszyńska
Beata
B
Kołaczkowski
Marcin
M
Kowalski
Piotr
P
Kowalska
Teresa
T
D008024:Ligands; D008968:Molecular Conformation; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*
D008024:Ligands; D010879:Piperazines; D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A