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Copyright © 1999 by Institute of Pharmacology Polish Academy of Sciences |
Pol. J. Pharmacol., 1999, 51, 415-421 ISSN 1230-6002 |
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Effect of the amide fragment on 5-HT1A receptor activity of some analogs of MP 3022.
M.H. PALUCHOWSKA, S. CHARAKCHIEVA-MINOL, E. TATARCZYŃSKA, A. KŁODZIŃSKA. Pol. J. Pharmacol., 1999, 51, 415-421. A new set (3-11) of analogs of MP 3022 (1) containing the amide bond inserted into the intermediate chain linking the terminal heteroaromatic and 1-(2-methoxyphenyl)piperazine moieties were prepared and their 5-HT1A and 5-HT2A receptor affinities were determined. Only compounds with trimethylene chain between amide and arylpiperazine fragments (5a, 5b, 7a, 7b and 11) showed satisfactory affinity for 5-HT1A receptor (Ki = 42–87 nM) and high 5-HT2A/5-HT1A selectivity. The new 5-HT1A receptor ligands were investigated in vivo to determine their 5-HT1A agonistic or antagonistic properties. Compounds 7a and 7b with terminal indazole fragment as well as 11 with phenyl substituent behaved like weak 5-HT1A receptor antagonists. The structure-affinity relationship studies in this series of compounds revealed that the amide group along with the terminal aromatic fragments contributed to interaction with 5-HT1A receptor sites, whereas in vivo results indicated that introduction of the amide group into presented arylpiperazine structures was not a profitable modification for their 5-HT1A functional activity. Key words: 5-HT1A ligands, structure-activity relationship |
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