Novel substituted pyrimidines as HCV replication (replicase) inhibitors.

  title={Novel substituted pyrimidines as HCV replication (replicase) inhibitors.},
  author={Cecil D. Kwong and Jeremy L Clark and Anita T Fowler and Feng Geng and Hollis S Kezar and Abhijit Roychowdhury and Robert C. Reynolds and Joseph A. Maddry and Subramaniam Ananthan and John A. Secrist and Neng-Yang Shih and John J. Piwinski and Cheng Li and Boris Feld and Hsueh-Cheng Huang and Xiao Mei Tong and F George Njoroge and Ashok Arasappan},
  journal={Bioorganic & medicinal chemistry letters},
  volume={22 2},
Compound 1 was identified as a HCV replication inhibitor from screening/early SAR triage. Potency improvement was achieved via modulation of substituent on the 5-azo linkage. Due to potential toxicological concern, the 5-azo linkage was replaced with 5-alkenyl or 5-alkynyl moiety. Analogs containing the 5-alkynyl linkage were found to be potent inhibitors of HCV replication. Further evaluation identified compounds 53 and 63 with good overall profile, in terms of replicon potency, selectivity… CONTINUE READING

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