Synthesis and serotonin receptor activity of the arylpiperazine alkyl/propoxy derivatives of new azatricycloundecanes.
A set of 36 arylpiperazine derivatives with two novel complex terminal imide fragments, 8,11-dimethyl-3,5-dioxo-4-azatricyclo[5.2.2.0(2,6)]undec-8-en-1-yl acetate and 1,11-dimethyl-4-azatricyclo[5.2.2.0(2,6)]undecane-3,5,8-trione, were synthesized and tested for their affinity for 5-HT(1A) and 5-HT(2A) receptors. The Fujita-Ban analysis showed that the influence of structural modifications on the affinity for both receptor subtypes is additive and that the activity of similar compounds could be predicted with high accuracy. Compounds 46, 48 and 18 out of 14 screened in a functional model of anxiety and depression demonstrated antidepressant activity in the forced swimming tests in mice, and were devoid of neurotoxic effects (chimney test in mice).
Bojarski
A J
AJ
Department of Medicinal Chemistry, Institute of Pharmacology of the Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland.
Kuran
B
B
Kossakowski
J
J
Kozioł
A
A
Jagiełło-Wójtowicz
E
E
Chodkowska
A
A
D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis*; D001007:Anxiety / Q000188:drug therapy; D003863:Depression / Q000188:drug therapy; D051379:Mice; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000928:Antidepressive Agents; D044402:Receptor, Serotonin, 5-HT2A; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A