Atropisomerism Observed in Indometacin Derivatives

To elucidate the active conformation of indometacin that differentiates between cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), the stereochemistry around the N-benzoylated indole moiety of indometacin was studied. Resolution of stable atropisomers as representative conformations was found to be possible by restricting rotation about the N−C7′ and/or C7′−C1′ bond. Only the aR-isomer showed specific inhibition of COX-1, and COX-2 was not inhibited by either atropisomer.