Conformation and atropisomeric properties of indometacin derivatives.

Authors :: Wakamatsu S
Takahashi Y
Tabata H
Oshitari T
Tani N
Azumaya I
Katsumoto Y
Tanaka T
Hosoi S
Natsugari H
Takahashi H
Source :: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2013 May 27; Vol. 19 (22), pp. 7056-63. Date of Electronic Publication: 2013 Apr 09.
Publication Year :: 2013
Abstract: The stereochemistry around the N-benzoylated indole moiety of indometacin was studied by restricting the rotation about the N-C7' and/or C7'-C1' bond. In the 2',6'-disubstituted ones, an atropisomeric property was found and the atropoisomers were separated and isolated as stable forms. Their biological abilities to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were examined. Only the aR-isomer showed specific inhibition of COX-1, and COX-2 was not inhibited by either atropisomer. Conformational analysis in NMR studies and X-ray crystallography, and CD spectra in combination with calculations were utilized to elucidate the bioactive conformations.<br /> (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)