Journal of Combinatorial Chemistry 2007-01-01

Design and synthesis of an array of selective androgen receptor modulators.

Ryan P Trump, Jean-Baptiste E Blanc, Eugene L Stewart, Peter J Brown, Matilde Caivano, David W Gray, William J Hoekstra, Timothy M Willson, Bajin Han, Philip Turnbull

Index: J. Comb. Chem. 9 , 107-114, (2007)

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Abstract

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.