title: Conformation and atropisomeric properties of indometacin derivatives.
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.
authors.affiliation: School of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Tokyo 173-8605, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Wakamatsu
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Tabata
authors.forename: Tetsuta
authors.initials: T
authors.lastname: Oshitari
authors.forename: Norihiko
authors.initials: N
authors.lastname: Tani
authors.forename: Isao
authors.initials: I
authors.lastname: Azumaya
authors.forename: Yukiteru
authors.initials: Y
authors.lastname: Katsumoto
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Shinzo
authors.initials: S
authors.lastname: Hosoi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Natsugari
authors.forename: Hideyo
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D018360:Crystallography, X-Ray; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D007213:Indomethacin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D016861:Cyclooxygenase Inhibitors; D007213:Indomethacin