Discovery of MK-1220: A Macrocyclic Inhibitor of Hepatitis C Virus NS3/4A Protease with Improved Preclinical Plasma Exposure.

@article{Rudd2011DiscoveryOM,
  title={Discovery of MK-1220: A Macrocyclic Inhibitor of Hepatitis C Virus NS3/4A Protease with Improved Preclinical Plasma Exposure.},
  author={Michael T. Rudd and John A. McCauley and John W Butcher and Joseph J Romano and Charles J McIntyre and Kevin T Nguyen and Kevin F Gilbert and Kimberly J Bush and M. Katharine Holloway and John Swestock and Bang-Lin Wan and Steven S. Carroll and Jillian M Dimuzio and Donald J. Graham and Steven W. Ludmerer and Mark W Stahlhut and Christine M Fandozzi and Nicole Trainor and David B. Olsen and Joseph P Vacca and Nigel J. Liverton},
  journal={ACS medicinal chemistry letters},
  year={2011},
  volume={2 3},
  pages={207-12}
}
The discovery of MK-1220 is reported along with the development of a series of HCV NS3/4A protease inhibitors containing a P2 to P4 macrocyclic constraint with improved preclinical pharmacokinetics. Optimization of the P2 heterocycle substitution pattern as well as the P3 amino acid led to compounds with greatly improved plasma exposure following oral dosing in both rats and dogs while maintaining excellent enzyme potency and cellular activity. These studies led to the identification of MK-1220… CONTINUE READING

From This Paper

Figures, tables, and topics from this paper.

References

Publications referenced by this paper.
Showing 1-10 of 31 references

AnNS 3 protease inhibitor with antiviral e ff ects in humans infected with hepatitis C virus

  • D. Lamarre, P. C. Anderson, M. Bailey, P. Beaulieu, G. Bolger
  • Curr . Top . Med . Chem . ( Sharjah , United Arab…
  • 2010

Preparation of macrocyclic compounds as HCV NS 3 protease inhibitors

  • M. K. Holloway, N. J. Liverton, S. W. Ludmerer, J. A. McCauley, D. B. Olsen
  • J . Med . Chem .
  • 2010

Boceprevir : NS 3 protease inhibitor treatment of chronic hepatitis C

  • C. Campas, R. Pandian, J. Bolos, R. Castaner
  • Curr . Med . Chem .
  • 2009

In vitro resistance pro fi le of the hepatitis C virus NS 3 / 4 A protease inhibitor TMC 435

  • O. Lenz, T. Verbinnen, T.-I. Lin, L. Vijgen, M. D. Cummings
  • Antimicrob . Agents Chemother .
  • 2009

Similar Papers

Loading similar papers…