Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981.

  title={Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981.},
  author={Tim Luker and Roger Bonnert and Steve Brough and Anthony R Cook and Mark R. Dickinson and Iain G. Dougall and Chris J Logan and Rukhsana T Mohammed and Stuart W Paine and Hitesh J. Sanganee and Carol Sargent and Jerzy A Schmidt and Simon Teague and Stephen Thom},
  journal={Bioorganic & medicinal chemistry letters},
  volume={21 21},
Novel indole-3-thio-, 3-sulfonyl- and 3-oxy-aryl-1-acetic acids are reported which are potent, selective antagonists of the chemoattractant receptor-homologous expressed on Th2 lymphocytes receptor (CRTh2 or DP2). Optimization required maintenance of high CRTh2 potency whilst achieving a concomitant reduction in rates of metabolism, removal of cyp p450 inhibition and minimization of aldose reductase and aldehyde reductase activity. High quality compounds suitable for in vivo studies are… CONTINUE READING
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Pharmacokinetic Optimization in Drug Research: Biological, Physicochemical and Computational Strategies

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Purified human recombinant aldehyde reductase ( ALR 1 ) and aldose reductase ( ALR 2 ) were kindly provided by Dr K . Bohren

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