| Autor: |
Forbes, I. T., Dabbs, S., Duckworth, D. M., Ham, P., Jones, G. E., King, F. D., Saunders, D. V., Blaney, F. E., Naylor, C. B., Baxter, G. S., Blackburn, T. P., Kennett, G. A., Wood, M. D. |
| Zdroj: |
Journal of Medicinal Chemistry; December 6, 1996, Vol. 39 Issue: 25 p4966-4977, 12p |
| Abstrakt: |
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-HT2C receptor binding site. Small molecule modeling studies have been used to define a region in space which is allowed at the 5-HT2C receptor but disallowed at the 5-HT2A receptor. In a complementary approach, docking of 2 into our model of the 5-HT2C 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-HT2C receptor for leucine residues in the 5-HT2A receptor is believed to account for the observed 5-HT2C/5-HT2A selectivity with 2. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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