Minimizing the Contribution of Enterohepatic Recirculation to Clearance in Rat for the NCINI Class of Inhibitors of HIV.

  title={Minimizing the Contribution of Enterohepatic Recirculation to Clearance in Rat for the NCINI Class of Inhibitors of HIV.},
  author={L. Fader and R. Carson and S. Morin and F. Bilodeau and Catherine Chabot and Ted Halmos and M. Bailey and S. Kawai and R. Coulombe and S. LaPlante and K. Mekhssian and A. Jakalian and M. Garneau and J. Duan and S. W. Mason and B. Simoneau and C. Fenwick and Y. Tsantrizos and C. Yoakim},
  journal={ACS medicinal chemistry letters},
  volume={5 6},
  • L. Fader, R. Carson, +16 authors C. Yoakim
  • Published 2014
  • Biology, Medicine
  • ACS medicinal chemistry letters
  • A scaffold replacement approach was used to identifying the pyridine series of noncatalytic site integrase inhibitors. These molecules bind with higher affinity to a tetrameric form compared to a dimeric form of integrase. Optimization of the C6 and C4 positions revealed that viruses harboring T124 or A124 amino acid substitutions are highly susceptible to these inhibitors, but viruses having the N124 amino acid substitution are about 100-fold less susceptible. Compound 20 had EC50 values <10… CONTINUE READING
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