Himbacine derived thrombin receptor (PAR-1) antagonists: Structure–activity relationship of the lactone ring

The structure–activity relationship (SAR) of the lactone ring of himbacine derived thrombin receptor (PAR-1) antagoinsts (e.g., 2–5) is described. The effect of the lactone carbonyl group on binding to PAR-1 is dependent on the substitution pattern of the pyridine ring. A stereoselective intramolecular Michael addition reaction to the vinyl pyridine group was observed for these pyridine analogs of himbacine in basic conditions at elevated temperature.

The structure–activity relationship (SAR) of the lactone ring of himbacine derived thrombin receptor (PAR-1) antagoinsts is described.Figure optionsDownload as PowerPoint slide