Zobrazeno 1 - 10
of 53
pro vyhledávání: '"Robert J. Leadley"'
Autor:
Robert P. Schaum, Lakshmi Narasimhan, Agustin Casimiro-Garcia, Chad A. Van Huis, Danette Dudley, Kevin J. Filipski, Wayne L. Cody, Christopher F. Bigge, Michael Pamment, Jeremy J. Edmunds, Thomas B. McClanahan, Ronald J. Heemstra, Vaishali Sahasrabudhe, Robert J. Leadley, Igor Mochalkin, J. Thomas Peterson, Jeffrey T. Kohrt
Publikováno v:
Bioorganic & Medicinal Chemistry. 17:2501-2511
Aiming to improve upon previously disclosed Factor Xa inhibitors, a series of 4,4-disubstituted pyrrolidine-1,2-dicarboxamides were explored with the intent of increasing the projected human half-life versus 5 (projected human t1/2 = 6 h). A stereosp
Autor:
Robert D. McBane, Thomas Peterson, Krzysztof Karnicki, Waldemar E. Wysokinski, Robert J. Leadley, Sangita M. Baxi
Publikováno v:
Thrombosis and Haemostasis. 99:759-766
SummaryThe objective of this study was to determine if orally-administered PD0348292, a direct specific factor Xa inhibitor, inhibits thrombosis following porcine carotid arterial injury comparably to aspirin or clopidogrel alone or in combination. W
Autor:
Christopher F. Bigge, Robert P. Schaum, Kathleen M. Welch, John W. Bryant, Chad A. Van Huis, Tawny K. Dahring, Vaisheli Sahasrabudhe, Ron Heemstra, Liguo Chi, Thomas B. McClanahan, Jeremy J. Edmunds, Jeffrey T. Kohrt, Staci Haarer, Erli Zhang, Robert J. Leadley, Wayne L. Cody, Lakshmi Narasimhan, Kevin J. Filipski, Agustin Casimiro-Garcia, Danette Dudley, Nancy Janiczek, J. Thomas Peterson
Publikováno v:
Chemical Biology & Drug Design. 70:100-112
Herein, we report the discovery of novel, proline-based factor Xa inhibitors containing a neutral P1 chlorophenyl pharmacophore. Through the additional incorporation of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one 22, as a P4 pharmacophore, we discov
Autor:
Wayne L. Cody, Staci Haarer, Erli Zhang, Chad A. Van Huis, Christopher F. Bigge, Lakshmi Narasimhan, Robert P. Schaum, John W. Bryant, Agustin Casimiro-Garcia, Thomas B. McClanahan, Danette Dudley, Kevin J. Filipski, Robert J. Leadley, Kathleen M. Welch, Jeremy J. Edmunds, Ronald J. Heemstra, Nancy Janiczek, Jeffrey T. Kohrt, J. Thomas Peterson
Publikováno v:
Chemical Biology & Drug Design. 69:444-450
A novel series of pyrrolidine-1,2-dicarboxamides was discovered as factor Xa inhibitors using structure-based drug design. This series consisted of a neutral 4-chlorophenylurea P1, a biphenylsulfonamide P4 and a D-proline scaffold (1, IC(50) = 18 nM)
Autor:
M. Urooj Zafar, Valentin Fuster, Michael E. Farkouh, James H. Chesebro, Robert J. Leadley, Julia Crook, Daichi Shimbo, Julio I. Osende, Stella Palencia
Publikováno v:
Thrombosis and Haemostasis. 97:487-492
SummaryIt was the objective of this study to evaluate the anti-thrombotic potency of direct factor-Xa inhibition with ZK-807834 in stable coronary patients, using an ex-vivo model of arterial thrombus formation. Tissue factor pathway is important in
Autor:
T R Johnson, Kathy Welch, Sangita M. Baxi, Thomas B. McClanahan, Liguo Chi, Weston R. Gould, Robert J. Leadley, Kamlai Saiya-Cork
Publikováno v:
Journal of Thrombosis and Haemostasis. 4:834-841
Summary. Background: Many compounds currently in development for treatment of thrombotic disorders demonstrate high specificity for single targets of blood coagulation such as factor Xa (FXa) or thrombin. Aim: The aim of this study is to determine if
Autor:
Chad A. Van Huis, Jeremy J. Edmunds, Kenneth J. Shaw, Marc Whitlow, Arnaiz Damian O, Marc Adler, Cuiman Cai, David R. Light, Kamlai Saiya-Cork, J. Adam Willardsen, Lakshmi Narasimhan, Erli Zhang, Stephen T. Rapundalo, Kevin J. Filipski, Wayne L. Cody, Kirk Mclean, Danette Dudley, Jeffrey T. Kohrt, Cecile McKnight, Robert J. Leadley, Yuo-Ling Chou
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 15:4752-4756
The activated Factor VII/tissue factor complex (FVIIa/TF) plays a key role in the formation of blood clots. Inhibition of this complex may lead to new antithrombotic drugs. An X-ray crystal structure of a fluoropyridine-based FVIIa/TF inhibitor bound
Autor:
Yun-Wen Peng, J. T. Peterson, Lisa A. Perrin, Richard L Schroeder, Robert J. Leadley, Weston R. Gould, Sangita M. Baxi
Publikováno v:
Journal of Thrombosis and Haemostasis. 3:733-741
Summary. Gas6 (encoded by growth arrest-specific gene 6) is a vitamin-K dependent protein highly homologous to coagulation protein S that is secreted from platelet α-granules and has recently been demonstrated to participate in platelet thrombus for
Autor:
Yong Mi Choi-Sledeski, Karen Brown, Robert J. Leadley, Gregory B. Poli, Vincent Mikol, Spada Alfred P, Yong Gong, Robert E. Kearney, Phillip Moxey, Charles J Kasiewski, Ross G. Bentley, Sébastien Maignan, Dennis Collussi, Pauls Henry W, Sam S. Rebello, Davis Roderick S, Valeria Chu, Gardner Charles J, Michael Becker, Jean-Pierre Guilloteau, Guyan Liang, Suzanne R Morgan
Publikováno v:
Journal of Medicinal Chemistry. 46:681-684
The discovery and SAR of ketopiperazino methylazaindole factor Xa inhibitors are described. Structure-activity data suggesting that this class of inhibitors does not bind in the canonical mode were confirmed by an X-ray crystal structure showing the
Autor:
Sebastian Maignan, Suzanne R Morgan, Robert J. Leadley, Valeria Chu, Gardner Charles J, Spada Alfred P, Pauls Henry W, Ross G. Bentley, Christopher T Dunwiddie, Klein Scott I, Jean-Pierre Guilloteau, Mark Czekaj, Karen Brown, Daniel L Cheney, Dennis J Colussi, Christopher L Heran, Kevin R. Guertin, Allison L Zulli, Yong Gong
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 12:1671-1674
Further optimization of the beta-aminoester class of factor Xa (fXa) inhibitors is described culminating in the identification of 9c (FXV673), a potent and selective factor Xa inhibitor with excellent in vivo anticoagulant activity. An X-ray structur