DISCOVERY OF NONSTEROIDAL ANDROGENS

Nonsteroidal androgens have not been reported. During studies to ident ify affinity ligands for the androgen receptor in our laboratory, we s ynthesized several electrophilic nonsteroidal ligands for the androgen receptor and examined their receptor binding affinity and ability to stimulate receptor-mediated transcriptional activation. We found that three of these ligands (1) bound the androgen receptor with affinity s imilar to that of dihydrotestosterone (the endogenous ligand) and (2) mimicked the effects of dihydrotestosterone on receptor-mediated trans criptional activation (i.e., they were receptor agonists). These studi es demonstrate that nonsteroidal ligands can be structurally modified to produce agonist activity. These ligands thus represent the first me mbers of a novel class of androgens with potential therapeutic applica tions in male fertility and hormone replacement therapy. (C) 1998 Acad emic Press.