-transparent.png){kind=logo}
Discovery of a novel, selective, and orally bioavailable class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position. 1997
D M Feng, and
S J Gardell, and
S D Lewis, and
M G Bock, and
Z Chen, and
R M Freidinger, and
A M Naylor-Olsen, and
H G Ramjit, and
R Woltmann, and
E P Baskin, and
J J Lynch, and
R Lucas, and
J A Shafer, and
K B Dancheck, and
I W Chen, and
S S Mao, and
J A Krueger, and
T R Hare, and
A M Mulichak, and
J P Vacca
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
A novel class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position has been discovered. Four of these thrombin inhibitors (13b,c,e and 14d) showed nanomolar potency (Ki 0.8-12 nM), 300-1500-fold selectivity for thrombin compared with trypsin, and good oral bioavailability (F = 40-76%) in rats or dogs. The neutral P1 was expected to increase metabolic stability and oral absorption. Identification of this novel aminopyridyl group at P1 was a key step in our search for a clinical candidate.
Related Publications
D M Feng, and
S J Gardell, and
S D Lewis, and
M G Bock, and
Z Chen, and
R M Freidinger, and
A M Naylor-Olsen, and
H G Ramjit, and
R Woltmann, and
E P Baskin, and
J J Lynch, and
R Lucas, and
J A Shafer, and
K B Dancheck, and
I W Chen, and
S S Mao, and
J A Krueger, and
T R Hare, and
A M Mulichak, and
J P Vacca
November 1996,
Journal of medicinal chemistry,
D M Feng, and
S J Gardell, and
S D Lewis, and
M G Bock, and
Z Chen, and
R M Freidinger, and
A M Naylor-Olsen, and
H G Ramjit, and
R Woltmann, and
E P Baskin, and
J J Lynch, and
R Lucas, and
J A Shafer, and
K B Dancheck, and
I W Chen, and
S S Mao, and
J A Krueger, and
T R Hare, and
A M Mulichak, and
J P Vacca
November 2006,
Bioorganic & medicinal chemistry letters,
D M Feng, and
S J Gardell, and
S D Lewis, and
M G Bock, and
Z Chen, and
R M Freidinger, and
A M Naylor-Olsen, and
H G Ramjit, and
R Woltmann, and
E P Baskin, and
J J Lynch, and
R Lucas, and
J A Shafer, and
K B Dancheck, and
I W Chen, and
S S Mao, and
J A Krueger, and
T R Hare, and
A M Mulichak, and
J P Vacca
September 1998,
Bioorganic & medicinal chemistry letters,
D M Feng, and
S J Gardell, and
S D Lewis, and
M G Bock, and
Z Chen, and
R M Freidinger, and
A M Naylor-Olsen, and
H G Ramjit, and
R Woltmann, and
E P Baskin, and
J J Lynch, and
R Lucas, and
J A Shafer, and
K B Dancheck, and
I W Chen, and
S S Mao, and
J A Krueger, and
T R Hare, and
A M Mulichak, and
J P Vacca
June 2004,
Bioorganic & medicinal chemistry letters,
D M Feng, and
S J Gardell, and
S D Lewis, and
M G Bock, and
Z Chen, and
R M Freidinger, and
A M Naylor-Olsen, and
H G Ramjit, and
R Woltmann, and
E P Baskin, and
J J Lynch, and
R Lucas, and
J A Shafer, and
K B Dancheck, and
I W Chen, and
S S Mao, and
J A Krueger, and
T R Hare, and
A M Mulichak, and
J P Vacca
May 2000,
Journal of medicinal chemistry,
D M Feng, and
S J Gardell, and
S D Lewis, and
M G Bock, and
Z Chen, and
R M Freidinger, and
A M Naylor-Olsen, and
H G Ramjit, and
R Woltmann, and
E P Baskin, and
J J Lynch, and
R Lucas, and
J A Shafer, and
K B Dancheck, and
I W Chen, and
S S Mao, and
J A Krueger, and
T R Hare, and
A M Mulichak, and
J P Vacca
July 2022,
ACS medicinal chemistry letters,
D M Feng, and
S J Gardell, and
S D Lewis, and
M G Bock, and
Z Chen, and
R M Freidinger, and
A M Naylor-Olsen, and
H G Ramjit, and
R Woltmann, and
E P Baskin, and
J J Lynch, and
R Lucas, and
J A Shafer, and
K B Dancheck, and
I W Chen, and
S S Mao, and
J A Krueger, and
T R Hare, and
A M Mulichak, and
J P Vacca
November 1999,
European journal of medicinal chemistry,
D M Feng, and
S J Gardell, and
S D Lewis, and
M G Bock, and
Z Chen, and
R M Freidinger, and
A M Naylor-Olsen, and
H G Ramjit, and
R Woltmann, and
E P Baskin, and
J J Lynch, and
R Lucas, and
J A Shafer, and
K B Dancheck, and
I W Chen, and
S S Mao, and
J A Krueger, and
T R Hare, and
A M Mulichak, and
J P Vacca
August 2003,
Journal of medicinal chemistry,
D M Feng, and
S J Gardell, and
S D Lewis, and
M G Bock, and
Z Chen, and
R M Freidinger, and
A M Naylor-Olsen, and
H G Ramjit, and
R Woltmann, and
E P Baskin, and
J J Lynch, and
R Lucas, and
J A Shafer, and
K B Dancheck, and
I W Chen, and
S S Mao, and
J A Krueger, and
T R Hare, and
A M Mulichak, and
J P Vacca
March 2000,
Acta crystallographica. Section D, Biological crystallography,
D M Feng, and
S J Gardell, and
S D Lewis, and
M G Bock, and
Z Chen, and
R M Freidinger, and
A M Naylor-Olsen, and
H G Ramjit, and
R Woltmann, and
E P Baskin, and
J J Lynch, and
R Lucas, and
J A Shafer, and
K B Dancheck, and
I W Chen, and
S S Mao, and
J A Krueger, and
T R Hare, and
A M Mulichak, and
J P Vacca
April 1999,
Bioorganic & medicinal chemistry letters,
