-transparent.png){kind=logo}
Discovery of vaniprevir (MK-7009), a macrocyclic hepatitis C virus NS3/4a protease inhibitor. 2010
John A McCauley, and
Charles J McIntyre, and
Michael T Rudd, and
Kevin T Nguyen, and
Joseph J Romano, and
John W Butcher, 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
Shi-Shan Mao, and
Mark W Stahlhut, and
Christine M Fandozzi, and
Nicole Trainor, and
David B Olsen, and
Joseph P Vacca, and
Nigel J Liverton
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. john_mccauley@merck.com
A new class of HCV NS3/4a protease inhibitors which contain a P2 to P4 macrocyclic constraint was designed using a molecular-modeling derived strategy. Exploration of the P2 heterocyclic region, the P2 to P4 linker, and the P1 side chain of this class of compounds via a modular synthetic strategy allowed for the optimization of enzyme potency, cellular activity, and rat liver exposure following oral dosing. These studies led to the identification of clinical candidate 35b (vaniprevir, MK-7009), which is active against both the genotype 1 and genotype 2 NS3/4a protease enzymes and has good plasma exposure and excellent liver exposure in multiple species.
Related Publications
John A McCauley, and
Charles J McIntyre, and
Michael T Rudd, and
Kevin T Nguyen, and
Joseph J Romano, and
John W Butcher, 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
Shi-Shan Mao, and
Mark W Stahlhut, and
Christine M Fandozzi, and
Nicole Trainor, and
David B Olsen, and
Joseph P Vacca, and
Nigel J Liverton
February 1999,
Antiviral research,
John A McCauley, and
Charles J McIntyre, and
Michael T Rudd, and
Kevin T Nguyen, and
Joseph J Romano, and
John W Butcher, 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
Shi-Shan Mao, and
Mark W Stahlhut, and
Christine M Fandozzi, and
Nicole Trainor, and
David B Olsen, and
Joseph P Vacca, and
Nigel J Liverton
December 1998,
Antiviral research,
John A McCauley, and
Charles J McIntyre, and
Michael T Rudd, and
Kevin T Nguyen, and
Joseph J Romano, and
John W Butcher, 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
Shi-Shan Mao, and
Mark W Stahlhut, and
Christine M Fandozzi, and
Nicole Trainor, and
David B Olsen, and
Joseph P Vacca, and
Nigel J Liverton
August 2006,
Bioorganic & medicinal chemistry letters,
John A McCauley, and
Charles J McIntyre, and
Michael T Rudd, and
Kevin T Nguyen, and
Joseph J Romano, and
John W Butcher, 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
Shi-Shan Mao, and
Mark W Stahlhut, and
Christine M Fandozzi, and
Nicole Trainor, and
David B Olsen, and
Joseph P Vacca, and
Nigel J Liverton
April 2012,
Bioorganic & medicinal chemistry letters,
John A McCauley, and
Charles J McIntyre, and
Michael T Rudd, and
Kevin T Nguyen, and
Joseph J Romano, and
John W Butcher, 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
Shi-Shan Mao, and
Mark W Stahlhut, and
Christine M Fandozzi, and
Nicole Trainor, and
David B Olsen, and
Joseph P Vacca, and
Nigel J Liverton
September 2012,
Clinical therapeutics,
John A McCauley, and
Charles J McIntyre, and
Michael T Rudd, and
Kevin T Nguyen, and
Joseph J Romano, and
John W Butcher, 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
Shi-Shan Mao, and
Mark W Stahlhut, and
Christine M Fandozzi, and
Nicole Trainor, and
David B Olsen, and
Joseph P Vacca, and
Nigel J Liverton
November 2008,
Recent patents on anti-infective drug discovery,
John A McCauley, and
Charles J McIntyre, and
Michael T Rudd, and
Kevin T Nguyen, and
Joseph J Romano, and
John W Butcher, 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
Shi-Shan Mao, and
Mark W Stahlhut, and
Christine M Fandozzi, and
Nicole Trainor, and
David B Olsen, and
Joseph P Vacca, and
Nigel J Liverton
October 2016,
Current opinion in pharmacology,
John A McCauley, and
Charles J McIntyre, and
Michael T Rudd, and
Kevin T Nguyen, and
Joseph J Romano, and
John W Butcher, 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
Shi-Shan Mao, and
Mark W Stahlhut, and
Christine M Fandozzi, and
Nicole Trainor, and
David B Olsen, and
Joseph P Vacca, and
Nigel J Liverton
January 2016,
Current medicinal chemistry,
John A McCauley, and
Charles J McIntyre, and
Michael T Rudd, and
Kevin T Nguyen, and
Joseph J Romano, and
John W Butcher, 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
Shi-Shan Mao, and
Mark W Stahlhut, and
Christine M Fandozzi, and
Nicole Trainor, and
David B Olsen, and
Joseph P Vacca, and
Nigel J Liverton
April 2012,
Bioorganic & medicinal chemistry letters,
John A McCauley, and
Charles J McIntyre, and
Michael T Rudd, and
Kevin T Nguyen, and
Joseph J Romano, and
John W Butcher, 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
Shi-Shan Mao, and
Mark W Stahlhut, and
Christine M Fandozzi, and
Nicole Trainor, and
David B Olsen, and
Joseph P Vacca, and
Nigel J Liverton
April 2012,
The Journal of organic chemistry,
