Synthesis and SAR of tetrahydropyrrolo[1,2-b][1,2,5]thiadiazol-2(3H)-one 1,1-dioxide analogues as highly potent selective androgen receptor modulators

Replacement of the 3-oxo group of 2-chloro-4-[(7R,7aS)-7-hydroxy-1,3-dioxotetrahydro-1H-pyrrolo[1,2c]imidazol-2(3H)-yl]-3-methylbenzonitrile resulted in a sulfamide series of selective androgen receptor modulator (SARM) agonists.

Graphical abstractHerein, we report the effects of replacing the 3-oxo group of 2 with a sulfonyl group (e.g., 3). These tetrahydropyrrolo[1,2-b][1,2,5]thiadiazol-2(3H)-one 1,1-dioxide analogues were found to be potent SARMs. Synthesis, binding and functional assay SAR, as well as in vivo characterization of a selected analogue in a standard rodent model are presented.Figure optionsDownload full-size imageDownload as PowerPoint slide