Sandbox Reserved 433: Difference between revisions
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==Introduction== | ==Introduction== | ||
Estrogen Receptor 2 beta/p-hydroxybenzene sulfonamide complexes | - Estrogen Receptor 2 beta/p-hydroxybenzene sulfonamide complexes | ||
- A series of p-hydroxybenzenesulphonamides ERb receptor agonists were discovered and several com-pounds identified had excellent selectivity over the related ERa receptor. One of these, compound 11, had an interesting binding conformation determined by X-ray and represents an excellent starting point in the quest for further selective ERb agonists. | |||
- There has been significant interest in the potential therapeutic benefit of selective ERb agonists to treat a variety of conditions including endometriosis3 and inflam-matory bowel disease | |||
- The amino acid sequence of the ligand binding domains between ERa and ERb is very highly conserved with only minor dif-ferences; Leu384 and Met421 in ERa is replaced by Met336 and Ile373 in ERb. The overall molecule is shown here with the <scene name='48/483890/Met336_and_ile373_in_erb/1'>Met336 and Ile373</scene> in ERb in blue to show their location. | |||
1. The amines were either purchased commercially or made via addition of a primary amine to an epoxide as shown in Scheme | |||
2. The compounds were tested as racemates and those of interest were separated by chiral HPLC. A wide range of analogues were prepared utilising the approach described. | |||
This is an overall scene with the beta sheets in purple and the alpha helices in ball and stick figures <scene name='48/483890/Ben_homyak_overall_structure/1'>Overall Structure</scene> | This is an overall scene with the beta sheets in purple and the alpha helices in ball and stick figures <scene name='48/483890/Ben_homyak_overall_structure/1'>Overall Structure</scene> | ||
