Synthesis and pharmacological evaluation of dimeric follicle-stimulating hormone receptor antagonists.

A series of homo- and heterodimeric compounds encompassing the follicle-stimulating hormone receptor (FSHR) antagonist (R)-1 and its inactive conformer (S)-1 connected through ethylene glycol spacers of various lengths is described. Evaluation of these compounds reveals that dimeric compounds, with a spacer of sufficient length, bearing two active copies of the antagonist are more potent relative to dimeric compounds in which one of the active pharmacophores is replaced by an inactive conformer. Interestingly, the opposite trend is observed if a short spacer is used, indicating that these compounds may be valuable tools to study FSHR dimerization in greater detail.