Sandbox Reserved 433

Introduction

- 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 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

Here is another scene with a rainbow diagram description of the whole protein

Overall Structure

Secondary Structure

-(alpha helices and beta sheets, insert green scenes here of each)

Polar and Nonpolar Groups

-(green scene of polar coloring and nonpolar coloring here) -surface groups vs. buried groups

Binding Interactions

Soo Lim put your stuff here

See Also

• [Estrogen Receptor]
• [1yy4]
• [1u3s]
• [1x78]
• [1qkn]

Credits

Introduction - Benjamin Homyak

Overall Structure - Marissa Burgess

Drug Binding Site - Soo Lim Park

References

1. ↑ Roberts LR, Armor D, Barker C, Bent A, Bess K, Brown A, Favor DA, Ellis D, Irving SL, MacKenny M, Phillips C, Pullen N, Stennett A, Strand L, Styles M. Sulfonamides as selective oestrogen receptor beta agonists. Bioorg Med Chem Lett. 2011 Oct 1;21(19):5680-3. Epub 2011 Aug 16. PMID:21885279 doi:10.1016/j.bmcl.2011.08.041