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Design and Synthesis of Indomethacin Analogues that inhibit P-glycoprotein and/or Multi-drug Resistant Protein without Cox Inhibitory Activity.

J Med Chem. 2012 Aug 23;

Authors: Arisawa M, Kasaya Y, Obata T, Sasaki T, Nakamura T, Araki T, Yamamoto K, Sasaki A, Yamano A, Ito M, Abe H, Ito Y, Shuto S


We designed and synthesized conformationally restricted analogues and regioisomers of the nonsteroidal anti-inflammatory drug indomethacin. Evaluation of the inhibitory effects of these compounds on COX, P-glycoprotein, and multidrug-resistance indicated that NSAIDS modulation of multidrug resistant P-glycoprotein and multidrug-resistant protein-1 is not associated with COX-1 and COX-2 inhibitory activities.

PMID: 22916727 [PubMed - as supplied by publisher]