We describe the design, using shape comparison and fast docking computer algorithms, and rapid parallel synthesis of a 1300 member array based on GSK7721, a 4-aminobenzonitrile androgen receptor (AR) antagonist identified by focused screening of the GSK compound collection. The array yielded 352 submicromolar and 17 subnanomolar AR agonists as measured by a cell-based reporter gene functional assay. The rapid synthesis of a large number of active compounds provided valuable information in the optimization of AR modulators, which may be useful in treating androgen deficiency in aging males.
Trump, R. P., Blanc, J-B. E., Stewart, E. L., Brown, P. J., Caivano, M., Gray, D. W., Hoekstra, W. J., Willson, T. M., Han, B., & Turnbull, P. (2007). Design and synthesis of an array of selective androgen receptor modulators. Journal of Combinatorial Chemistry, 9(1), 107-14. https://doi.org/10.1021/cc060096e