Structure-activity relationship studies of CNS agents. Part VIII. Bulk tolerance around the protonation center of 4-substituted 1-(3-chlorophenyl)piperazines at 5-HT1A and 5-HT2 receptors.
The effect of a steric hindrance around the protonation center of the model 4-substituted 1-(3-chlorophenyl)-piperazines 1-9 and 11-14 on their affinity for 5-HT1A and 5-HT2 receptor sites was investigated. Additional evidence for hydrophobic interactions between the N-4 hydrocarbon substituents and 5-HT1A receptors has been presented. However, the hydrophobic forces play a minor role in stabilization of the bioactive complex with 5-HT2 receptors. It has also been found that even bulky substituents around the protonation center of 1-aryl-piperazines are well tolerated at both 5-HT1A and 5-HT2 sites.
Mokrosz
J L
JL
Department of Medicinal Chemistry, Polish Academy of Sciences, Kraków.
Charakchieva-Minol
S
S
Paluchowska
M H
MH
Cegła
M T
MT
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C015068:1-(3-chlorophenyl)piperazine