-transparent.png){kind=logo}
Dual pro-drugs of 2'-C-methyl guanosine monophosphate as potent and selective inhibitors of hepatitis C virus. 2011
Christopher McGuigan, and
Karolina Madela, and
Mohamed Aljarah, and
Arnaud Gilles, and
Srinivas K Battina, and
Changalvala V S Ramamurty, and
C Srinivas Rao, and
John Vernachio, and
Jeff Hutchins, and
Andrea Hall, and
Alexander Kolykhalov, and
Geoffrey Henson, and
Stanley Chamberlain
Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK. mcguigan@cf.ac.uk
We have previously reported the power of combining a 5'-phosphoramidate ProTide, phosphate pro-drug, motif with a 6-methoxy purine pro-drug entity to generate highly potent anti-HCV agents, leading to agents in clinical trial. We herein extend this work with the disclosure that a variety of alternative 6-substituents are tolerated. Several compounds exceed the potency of the prior 6-methoxy leads, and in almost every case the ProTide is several orders of magnitude more potent than the parent nucleoside. We also demonstrate that these agents act as pro-drugs of 2'-C-methyl guanosine monophosphate. We have also reported the novel use of hepatocyte cell lysate as an ex vivo model for ProTide metabolism.
Related Publications
Christopher McGuigan, and
Karolina Madela, and
Mohamed Aljarah, and
Arnaud Gilles, and
Srinivas K Battina, and
Changalvala V S Ramamurty, and
C Srinivas Rao, and
John Vernachio, and
Jeff Hutchins, and
Andrea Hall, and
Alexander Kolykhalov, and
Geoffrey Henson, and
Stanley Chamberlain
May 2007,
Bioorganic & medicinal chemistry letters,
Christopher McGuigan, and
Karolina Madela, and
Mohamed Aljarah, and
Arnaud Gilles, and
Srinivas K Battina, and
Changalvala V S Ramamurty, and
C Srinivas Rao, and
John Vernachio, and
Jeff Hutchins, and
Andrea Hall, and
Alexander Kolykhalov, and
Geoffrey Henson, and
Stanley Chamberlain
May 2007,
Bioorganic & medicinal chemistry letters,
Christopher McGuigan, and
Karolina Madela, and
Mohamed Aljarah, and
Arnaud Gilles, and
Srinivas K Battina, and
Changalvala V S Ramamurty, and
C Srinivas Rao, and
John Vernachio, and
Jeff Hutchins, and
Andrea Hall, and
Alexander Kolykhalov, and
Geoffrey Henson, and
Stanley Chamberlain
February 2015,
Bioorganic & medicinal chemistry letters,
Christopher McGuigan, and
Karolina Madela, and
Mohamed Aljarah, and
Arnaud Gilles, and
Srinivas K Battina, and
Changalvala V S Ramamurty, and
C Srinivas Rao, and
John Vernachio, and
Jeff Hutchins, and
Andrea Hall, and
Alexander Kolykhalov, and
Geoffrey Henson, and
Stanley Chamberlain
April 2015,
Journal of medicinal chemistry,
Christopher McGuigan, and
Karolina Madela, and
Mohamed Aljarah, and
Arnaud Gilles, and
Srinivas K Battina, and
Changalvala V S Ramamurty, and
C Srinivas Rao, and
John Vernachio, and
Jeff Hutchins, and
Andrea Hall, and
Alexander Kolykhalov, and
Geoffrey Henson, and
Stanley Chamberlain
December 2016,
ACS medicinal chemistry letters,
Christopher McGuigan, and
Karolina Madela, and
Mohamed Aljarah, and
Arnaud Gilles, and
Srinivas K Battina, and
Changalvala V S Ramamurty, and
C Srinivas Rao, and
John Vernachio, and
Jeff Hutchins, and
Andrea Hall, and
Alexander Kolykhalov, and
Geoffrey Henson, and
Stanley Chamberlain
April 2008,
Antimicrobial agents and chemotherapy,
Christopher McGuigan, and
Karolina Madela, and
Mohamed Aljarah, and
Arnaud Gilles, and
Srinivas K Battina, and
Changalvala V S Ramamurty, and
C Srinivas Rao, and
John Vernachio, and
Jeff Hutchins, and
Andrea Hall, and
Alexander Kolykhalov, and
Geoffrey Henson, and
Stanley Chamberlain
February 2008,
Bioorganic & medicinal chemistry,
Christopher McGuigan, and
Karolina Madela, and
Mohamed Aljarah, and
Arnaud Gilles, and
Srinivas K Battina, and
Changalvala V S Ramamurty, and
C Srinivas Rao, and
John Vernachio, and
Jeff Hutchins, and
Andrea Hall, and
Alexander Kolykhalov, and
Geoffrey Henson, and
Stanley Chamberlain
September 2006,
Antiviral research,
Christopher McGuigan, and
Karolina Madela, and
Mohamed Aljarah, and
Arnaud Gilles, and
Srinivas K Battina, and
Changalvala V S Ramamurty, and
C Srinivas Rao, and
John Vernachio, and
Jeff Hutchins, and
Andrea Hall, and
Alexander Kolykhalov, and
Geoffrey Henson, and
Stanley Chamberlain
January 2007,
Antiviral chemistry & chemotherapy,
Christopher McGuigan, and
Karolina Madela, and
Mohamed Aljarah, and
Arnaud Gilles, and
Srinivas K Battina, and
Changalvala V S Ramamurty, and
C Srinivas Rao, and
John Vernachio, and
Jeff Hutchins, and
Andrea Hall, and
Alexander Kolykhalov, and
Geoffrey Henson, and
Stanley Chamberlain
October 2000,
Bioorganic & medicinal chemistry letters,
