Evaluation of 1‐arylpiperazine derivative of hydroxybenzamides as 5‐HT1A and 5‐HT7 serotonin receptor ligands: An experimental and molecular modeling approach |
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| Authors: | Piotr Kowalski Jolanta Ja?kowska Andrzej J Bojarski Beata Duszyńska Adam Bucki Marcin Ko?aczkowski |
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| Institution: | 1. Institute of Organic Chemistry and Technology, Cracow University of Technology, 31‐155 Kraków, Poland;2. Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 31‐343 Kraków, Poland;3. Department of Pharmaceutical Chemistry, Jagiellonian University Collegium Medicum, 30‐688 Kraków, Poland |
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| Abstract: | The synthesis and evaluation as 5‐HT1A and 5‐HT7 serotonin receptor ligands of the two sets of O‐substituted hydroxybenzamides, structurally related to 2‐{3‐4‐(2‐methoxyphenyl)piperazin‐1‐yl]propoxy}benzamide ( 1 ), (Ki 5‐HT1A = 21 nM, 5‐HT7 = 234 nM) are reported. To affect the affinity for 5‐HT1A and 5‐HT7 receptors, an amide moiety ( 2 , 3 , 4 , 5 , 6 ) and a hydrocarbon chain length ( 7 , 8 , 9 , 10 ) were modified. The serotonergic activity of compounds 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 was generally higher in the case of 5‐HT1A receptors compared with 5‐HT7 ones; the most active 5‐HT1A ligands being meta‐isomer 2 (Ki = 7 nM) and both analogs of 1 with the longest spacer, i.e., penta‐ and hexa‐methylene derivatives 9 and 10 (Ki = 4 and 3 nM, respectively). The observed biological properties of compounds 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 were elucidated using molecular modeling procedures. J. Heterocyclic Chem., (2010). |
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