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.
School of Pharmaceutical Sciences, Teikyo University, 1091-1, Midori-ku, Sagamihara, Kanagawa 252-5195, Japan. hide-tak@pharm.teikyo-u.ac.jp
Hideyo
H
Takahashi
Shintaro
S
Wakamatsu
Hidetsugu
H
Tabata
Tetsuta
T
Oshitari
Ayako
A
Harada
Keizo
K
Inoue
Hideaki
H
Natsugari
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; 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; D008958:Models, Molecular; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007213:Indomethacin