| Autor: |
Forbes IT; SmithKline Beecham Pharmaceuticals, Discovery Research, Harlow, Essex, England., Dabbs S, Duckworth DM, Ham P, Jones GE, King FD, Saunders DV, Blaney FE, Naylor CB, Baxter GS, Blackburn TP, Kennett GA, Wood MD |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1996 Dec 06; Vol. 39 (25), pp. 4966-77. |
| DOI: |
10.1021/jm960571v |
| 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-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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
