Structure-Activity Relationship Studies of CNS Agents,Part 31[1]: Analogs of MP 3022 with a Different Number of Nitrogen Atoms in the Heteroaromatic Fragment — New 5-HT1A Receptor Ligands |
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Authors: | Maria H. Paluchowska,Anna Dere -Weso ek,Jerzy L. Mokrosz ,Sijka Charakchieva-Minol,Ewa Chojnacka-W jcik |
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Affiliation: | Maria H. Paluchowska,Anna Dereń-Wesońek,Jerzy L. Mokrosz (deceased),Sijka Charakchieva-Minol,Ewa Chojnacka-Wójcik |
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Abstract: | Two series of new MP 3022 analogs, i.e. 1-(o-methoxyphenyl)-4-n-propylpiperazines ( 3, 4a, 4b, 6–9 , and 12–13 ) and 2-(n-propyl)-1,2,3,4-tetrahydroisoquinolines ( 5a, 5b, 11a , and 11b ) containing a terminal heteroaromatic system with a different number of nitrogen atoms, were synthesized and their 5-HT1A/5-HT2A and α1 receptor affinity was assayed. The majority of investigated piperazines may be classified as non-selective 5-HT1A/5-HT2A/α1 receptor ligands. Compounds 3, 4a, 4b, 7–9a with the highest affinity for 5-HT1A receptors (Ki = 4–54 nM) were tested in vivo. Their functional activity was differentiated; while 3, 8 , and 9a behaved like weak antagonists of postsynaptic 5-HT1A receptors, 4b and 7 may be classified as potential partial 5-HT1A receptor agonists. Isomer 4a has characteristic features of a potential weak postsynaptic 5-HT1A receptor agonist. |
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Keywords: | 1-(2-methoxyphenyl)piperazines 5-HT1A receptor ligands α 1-adrenergic receptor ligands 5-HT1A receptor partial agonist 5-HT1A receptor antagonist |
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