Design and synthesis of an array of selective androgen receptor modulators

TY - JOUR

T1 - Design and synthesis of an array of selective androgen receptor modulators

AU - Trump, Ryan P.

AU - Blanc, Jean-Baptiste E.

AU - Stewart, Eugene L.

AU - Brown, Peter J.

AU - Caivano, Matilde

AU - Gray, David W.

AU - Hoekstra, William J.

AU - Willson, Timothy M.

AU - Han, Bajin

AU - Turnbull, Philip

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

U2 - 10.1021/cc060096e

DO - 10.1021/cc060096e

M3 - Article

C2 - 17206838

SN - 1520-4766

VL - 9

SP - 107

EP - 114

JO - Journal of Combinatorial Chemistry

JF - Journal of Combinatorial Chemistry

IS - 1

ER -