Amide bond surrogates: A study in thiophenesulfonamide based endothelin receptor antagonists

The potential proteolytic instability of the amide bond present in some ETA selective thiophenesulfonamide endothelin antagonists exemplified by TBC-10708 led us to investigate the replacement of this moiety with stable amide bond surrogates such as a trans double bond and an ethylene spacer. The effect of these replacements on the binding affinity is described.