Premium
Conformation and Atropisomeric Properties of Indometacin Derivatives
Author(s) -
Wakamatsu Shintaro,
Takahashi Yuka,
Tabata Hidetsugu,
Oshitari Tetsuta,
Tani Norihiko,
Azumaya Isao,
Katsumoto Yukiteru,
Tanaka Takeyuki,
Hosoi Shinzo,
Natsugari Hideaki,
Takahashi Hideyo
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201300064
Subject(s) - atropisomer , moiety , chemistry , cyclooxygenase , indometacin , stereochemistry , indole test , enzyme , biochemistry , prostaglandin endoperoxide synthase
The stereochemistry around the N ‐benzoylated indole moiety of indometacin was studied by restricting the rotation about the NC7′ 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 a R ‐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.