Forbes, IT and Dabbs, S and Duckworth, DM and Ham, P and Jones, GE and King, FD and Saunders, DV and Blaney, FE and Naylor, CB and Baxter, GS and Blackburn, TP and Kennett, GA and Wood, MD (1996) Synthesis, biological activity, and molecular modeling of selective 5-HT(2C/2B) receptor antagonists. J Med Chem , 39 (25) 4966 - 4977. 10.1021/jm960571v.
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The synthesis and biological activity are reported for a series of analogues of the previously published indole urea 2 (SB-206553), designed to probe the 5-HT(2C) receptor binding site. Small molecule modeling studies have been used to define a region in space which is allowed at the 5-HT(2C) receptor but disallowed at the 5-HT(2A) receptor. In a complementary approach, docking of 2 into our model of the 5-HT(2C) receptor has allowed us to propose a novel primary binding interaction for this series of diaryl ureas, involving a potential double hydrogen-bonding interaction between the urea carbonyl oxygen of the ligand and two serine residues in the receptor. The difference of two valine residues in the 5-HT(2C) receptor for leucine residues in the 5-HT(2A) receptor is believed to account for the observed 5-HT(2C)/5-HT(2A) selectivity with 2.
|Title:||Synthesis, biological activity, and molecular modeling of selective 5-HT(2C/2B) receptor antagonists.|
|Keywords:||Animals, Frontal Lobe, Indoles, Magnetic Resonance Spectroscopy, Models, Molecular, Pyridines, Radioligand Assay, Rats, Serotonin Antagonists|
|UCL classification:||UCL > School of BEAMS > Faculty of Maths and Physical Sciences > Chemistry|
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