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Modification of the Structure of 4, 6‐Disubstituted 2‐(4‐Alkyl‐1‐piperazinyl)pyridines: Synthesis and Their 5‐HT 2A Receptor Activity
Author(s) -
Paluchowska Maria H.,
Bojarski Andrzej J.,
Bugno Ryszard,
CharakchievaMinol Sijka,
Wesołowska Anna
Publication year - 2003
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200390006
Subject(s) - chemistry , in vivo , pyrimidine , 5 ht receptor , antagonist , stereochemistry , chemical synthesis , structure–activity relationship , benzotriazole , in vitro , receptor , serotonin , combinatorial chemistry , biochemistry , organic chemistry , biology , microbiology and biotechnology
Structure‐activity relationship studies of a series of novel 4, 6‐disubstituted 2‐(1‐piperazinyl)pyridines were conducted to revise our model of serotonin 5‐HT 2A receptor antagonist. Target compounds were synthesized using the benzotriazole‐assisted Katritzky method. The majority of those compounds were found to be selective 5‐HT 2A /5‐HT 1A receptor ligands, though less potent than their previously described pyrimidine counterparts. In particular, the three compounds 6 — 8 showed the highest 5‐HT 2A receptor affinity ( K i = 34—78 nM) and were classified as 5‐HT 2A antagonists in in vivo experiments. The influence of the structural modifications on the in vitro results was discussed; however, the elucidation of the role of the central core system requires further studies.