Recent advances in the development of selective androgen receptor modulators.

Background: The androgens testosterone and its more potent tissue metabolite 5-alpha-dihydrotesterone regulate diverse physiological process involving both reproductive and non-reproductive functions. Most of the signaling effects of androgens are mediated through the androgen receptor (AR), a member of the nuclear receptor superfamily of transcription factors. The AR has been a target for drug development focused on the treatment of pathological conditions arising from abnormal androgen levels or altered target tissue responsiveness, the improvement of physical performance and the regulation of male fertility. The primary focus for drug design has been the synthesis of chemicals to regulate the transcriptional activity of AR based on the structural and functional properties of the ligands, with a recent preference for selectively anabolic non-steroidals. A new class of molecules targeting androgen receptors called selective androgen receptor modulators is being developed, analogous to the clinically successful and at present marketed selective estrogen receptor modulators.

Objective/methods: This article highlights and reviews research advances in this field that have been published in patent literature since 2003.

Results/conclusion: The structural diversity of selective androgen receptor modulators has dramatically increased. Several compounds have emerged as clinical and preclinical candidates.