Structure-activity relationship studies of CNS agents--XVII. Spiro[piperidine-4',1-(1,2,3,4-tetrahydro-beta-carboline)] as a probe defining the extended topographic model of 5-HT1A receptors.
Spiro[piperidine-4',1-(1,2,3,4-tetrahydro-beta-carboline)] (10), its derivatives 11-15 and its analogs 16 and 17 were examined as ligands of serotonin 5-HT1A receptors. It was shown that compounds 12 and 14 had essentially the same 5-HT1A affinity as 1-phenylpiperazine and its rigid analog 7, whereas there were substantial differences in the steric arrangement of their crucial pharmacophores, i.e. aromatic and protonation centers. On the basis of the existing models and using the (+)-LSD structure as a template, a new, extended three-point topographic model of 5-HT1A receptors has been proposed.
Mokrosz
M J
MJ
Department of Medicinal Chemistry, Polish Academy of Sciences, Kraków.
Duszynska
B
B
Bojarski
A J
AJ
Mokrosz
J L
JL
D000818:Animals; D002491:Central Nervous System Agents / Q000737:chemistry / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008024:Ligands; D015335:Molecular Probes; D010880:Piperidines / Q000138:chemical synthesis / Q000378:metabolism*; D011487:Protein Conformation; D011869:Radioligand Assay; D051381:Rats; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002491:Central Nervous System Agents; D008024:Ligands; D015335:Molecular Probes; D010880:Piperidines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D013141:Spiro Compounds; C095306:spiro(piperidine-4',1-(1,2,3,4-tetrahydro-beta-carboline))