In vivo SAR was conducted through modification on structure I by replacement of the amide bond with amidate structures. This led to the identification of a novel series of imidazolopyrazole derivatives II as Selective Androgen Receptor Modulators (SARMs) with oral efficacy. The lead compound is a tissue-selective non-steroidal androgen receptor ligand with agonist activity in rat muscle and mixed agonist and antagonist activity in the rat prostate. The synthesis and in vivo SAR studies of this novel series of bicyclic structures is presented.