Pratt John K, Donner Pamela, McDaniel Keith F, Maring Clarence J, Kati Warren M, Mo Hongmei, Middleton Tim, Liu Yaya, Ng Teresa, Xie Qinghua, Zhang Rong, Montgomery Debra, Molla Akhteruzzaman, Kempf Dale J, Kohlbrenner William
Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA.
Bioorg Med Chem Lett. 2005 Mar 15;15(6):1577-82. doi: 10.1016/j.bmcl.2005.01.071.
N-1-Alkylamino and N-1-alkyloxy-4-hydroxyquinolon-3-yl benzothiadiazines were synthesized and evaluated as inhibitors of genotype 1 HCV polymerase. The N-1-alkyloxy derivatives were not potent inhibitors, however N-1-alkylamino derivatives displayed comparable potency to carbon analogs. Analogs with aliphatic substituents were significantly more potent than those with benzylic substituents against genotype 1a polymerase. The most potent inhibitors contained small alkyl or carbocyclic substituents and exhibited IC50's of 50-100 and 200-400 nM against genotype 1b and 1a HCV polymerase, respectively.
