Structural combination of established 5-HT(2A) receptor ligands: new aspects of the binding mode
Research output: Contribution to journal › Journal article › Research › peer-review
MH.MZ, MDL 100907, and altanserin are structurally similar 4-benzoyl-piperidine derivatives and are well accommodated to receptor interaction models. We combined structural elements of different high-affinity and selective 5-HT(2A) antagonists, as MH.MZ, altanserin, and SR 46349B, to improve the binding properties of new compounds. Three new derivatives were synthesized with a 4-benzoyl-piperidine moiety as the lead structure. The in vitro affinity of the novel compounds was determined by a [³H]MDL 100907 competition binding assay. The combination of MH.MZ and SR 46349B resulted in a compound (8) with a moderate affinity toward the 5-HT(2A) receptor (K(i) = 57 nm). The remarkably reduced affinity of other compounds (4a), (4b), and (4c) (K(i) = 411, 360 and 356 nm respectively) indicates that MH.MZ can only bind to the 5-HT(2A) receptor with the p-fluorophenylethyl residue in a sterically restricted hydrophobic binding pocket.
Original language | English |
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Journal | Chemical Biology & Drug Design (Online) |
Volume | 76 |
Issue number | 4 |
Pages (from-to) | 361-6 |
Number of pages | 6 |
ISSN | 1747-0277 |
DOIs | |
Publication status | Published - 1 Oct 2010 |
- Binding, Competitive, Combinatorial Chemistry Techniques, Fluorobenzenes, Hydrophobic and Hydrophilic Interactions, Ketanserin, Ligands, Phenols, Piperidines, Protein Binding, Pyridines, Receptor, Serotonin, 5-HT2A, Serotonin 5-HT2 Receptor Antagonists
Research areas
ID: 35304393