School of Pharmaceutical Sciences, Teikyo University, 1091-1, Midori-ku, Sagamihara, Kanagawa 252-5195, Japan.
Org Lett. 2011 Feb 18;13(4):760-3. doi: 10.1021/ol103008d. Epub 2011 Jan 20.
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.
为了阐明吲哚美辛区分环氧化酶-1（COX-1）和环氧化酶-2（COX-2）的活性构象，研究了吲哚美辛中 N-苯甲酰化吲哚部分周围的立体化学。通过限制 N-C7' 和/或 C7'-C1' 键的旋转，发现可以分离出稳定的对映异构体作为代表性构象。只有 aR-异构体对 COX-1 表现出特异性抑制作用，而 COX-2 两种对映异构体都没有被抑制。
