Figure 8.

Mapping of compound 19 (black) into the FXR ligand binding site. In comparison to the original ligand, compound 11 (white), 19 established additional hydrogen bonds (arrows) between the hydroxy group and Ser332/Tyr369. The hydrogen bond acceptor (red arrow) with His294 was observed in both compounds 11 and 19, respectively. Hydrogen bond-forming amino acids are depicted in ball-and-stick style. Three hydrophobic interactions (yellow spheres) were predicted to be identical for compounds 11 and 19. The piperazine moiety was not observed to form direct interactions with the receptor and could therefore be regarded as a solubility-enhancing spacer.