11beta-alkyl-Delta9-19-nortestosterone derivatives: high-affinity ligands and potent partial agonists of the androgen receptor

We report the synthesis of novel steroidal Androgen Receptor ligands comprising 11beta-alkyl-Delta(9)-derivatives of 19-nortestosterone. These compounds are structurally related to the antiprogestin, antiglucocorticoid, and antiandrogen drug mifepristone (RU486). Nortestosterone analogues bearing 11beta-octyl and 11beta-decyl side-chains bind tightly to recombinant AR protein (IC(50) = 6.6 nM and IC(50) = 0.8 nM), block AR dimerization, exhibit activity against LNCaP prostate Cancer cells, and comprise partial AR agonists with low antiglucocorticoid activity.