Zobrazeno 1 - 10
of 111
pro vyhledávání: '"Jules A. Shafer"'
Autor:
Robinson Kyle A, Terry A. Lyle, Audrey A. Wallace, Christina L. Newton, Zhongguo Chen, James Z. Deng, Cynthia Miller-Stein, Bobby J. Lucas, Daniel R. McMasters, Janetta M. Pellicore, Harold G. Selnick, Joseph J. Lynch, Rebecca B. White, Lawrence Kuo, Julie A. Krueger, Christopher S. Burgey, Bradley K. Wong, Youwei Yan, Joseph P. Vacca, S. Dale Lewis, Jules A. Shafer, Stephen J. Gardell, Philippe G. Nantermet
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 15:2771-2775
In this study, we have demonstrated that the critical hydrogen bonding motif of the established 3-aminopyrazinone thrombin inhibitors can be effectively mimicked by a 2-aminopyridine N-oxide. As this peptidomimetic core is more resistant toward oxida
Autor:
Christopher S. Burgey, Joseph J. Lynch, Bobby J. Lucas, Lawrence Kuo, Dennis L. Bohn, Jules A. Shafer, Bradley K. Wong, Rominder Singh, Janetta M. Pellicore, Cynthia Miller-Stein, Audrey A. Wallace, Franklin C. Clayton, Stephen J. Gardell, Terry A. Lyle, Maria T. Stranieri, Denise C. Welsh, Daniel R. McMasters, Philippe G. Nantermet, Elizabeth A. Lyle, Harold G. Selnick, Joseph P. Vacca, Zhongguo Chen, Jacquelynn J. Cook, Rebecca B. White, Youwei Yan, Richard C.A. Isaacs, Julie A. Krueger, S. Dale Lewis, Swati Pal, Robinson Kyle A
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 13:1353-1357
In this manuscript we demonstrate that a modification principally directed toward the improvement of the aqueous solubility (i.e., introduction a P3 pyridine N-oxide) of the previous lead compound afforded a new series of potent orally bioavailable P
Autor:
Bobby J. Lucas, Franklin C. Clayton, Daniel R. McMasters, James C. Barrow, Peter D. Williams, Robinson Kyle A, Theodore J. Detwiler, Yvonne M. Leonard, Sanderson Philip E, Julie A. Krueger, S. Dale Lewis, Rebecca B. White, Elizabeth A. Lyle, Cynthia Miller-Stein, William M. Sanders, Marie A. Holahan, Colleen M. McDonough, Youwei Yan, Jacquelynn J. Cook, Maria T. Stranieri, Joseph J. Lynch, Rominder Singh, G. R. Sitko, Lawrence Kuo, Terry A. Lyle, Craig A. Coburn, Zhongguo Chen, Dennis L. Bohn, Jules A. Shafer, Joseph P. Vacca, Audrey A. Wallace, Bruce D. Dorsey, Bradley K. Wong, Christopher S. Burgey, Stephen J. Gardell
Publikováno v:
Journal of Medicinal Chemistry. 46:461-473
Recent efforts in the field of thrombin inhibitor research have focused on the identification of compounds with good oral bioavailability and pharmacokinetics. In this manuscript we describe a metabolism-based approach to the optimization of the 3-(2
Publikováno v:
Journal of Biological Chemistry. 274:35046-35052
Plasma carboxypeptidase B (PCB) is an exopeptidase that exerts an antifibrinolytic effect by releasing C-terminal Lys and Arg residues from partially degraded fibrin. PCB is produced in plasma via limited proteolysis of the zymogen, pro-PCB. In this
Autor:
Jules A. Shafer, Charles N. Habecker, Joseph P. Vacca, William M. Sanders, Thomas J. Tucker, Zhonguo Chen, A. M. Mulichak, S. Dale Lewis, Gerald S. Ponticello, Adel M. Naylor-Olsen, Brian T. Phillips
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 8:1697-1702
A novel, nonpeptidyl thrombin inhibitor, L-636,619 (1), was identified via topological similarity searching over the Merck Corporate Sample Database. X-ray crystallographic studies determined the geometry for ligand binding to the enzyme. Chemical mo
Autor:
S. Dale Lewis, Elizabeth A. Lyle, I.-W. Chen, Julie A. Krueger, Jacquelynn J. Cook, Zhongguo Chen, Jiunn H. Lin, Joseph P. Vacca, Bruce D. Dorsey, Adel M. Naylor-Olsen, Jules A. Shafer, Joseph J. Lynch, Kellie J. Cutrona, Bobby J. Lucas, Colleen M. McDonough, Dona L. Dyer, Maria T. Stranieri, Sanderson Philip E, Kari Vastag, Stephen J. Gardell
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 8:817-822
Replacement of the amidinopiperidine P1 group of 3-benzylsulfonylamino-6-methyl-2-pyridinone acetamide thrombin inhibitor L-373,890 (2) with a mildly basic 5-linked 2-amino-6-methylpyridine results in an equipotent compound L-374,087 (5, Ki = 0.5 nM)
Autor:
Shi-Shan Mao, E P Baskin, Julie A. Krueger, Mark G. Bock, Dong-Mei Feng, A. M. Mulichak, Stephen J. Gardell, Roger M. Freidinger, Lucas R, Ramjit Hg, Jules A. Shafer, S. D. Lewis, R Woltmann, K B Dancheck, Timothy R. Hare, J.J. Lynch, Adel M. Naylor-Olsen, I.-W. Chen, Zhongguo Chen, Joe P. Vacca
Publikováno v:
Journal of Medicinal Chemistry. 40:3726-3733
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 compa
Publikováno v:
Journal of Biological Chemistry. 272:30275-30282
The kinetic pathway for the Na+-induced slow → fast transition of thrombin was characterized. The slow form was shown to consist of two conformers in a 3:1 ratio (E S2:E S1) at 5 °C, pH 7.4, Γ/2 0.3. E S2 binds Na+ 3 orders of magnitude faster th
Autor:
K.J. Stauffer, Jules A. Shafer, Stephen F. Brady, S. D. Lewis, John T. Sisko, D. F. Veber, Howard Qiu, Assunta S. Ng, Ruth F. Nutt, Michael J. Bogusky, Christiana D. Colton
Publikováno v:
Bioorganic & Medicinal Chemistry. 3:1063-1078
We report structure-activity investigations in a series of tripeptide amide inhibitors of thrombin, and the development of a series of highly potent active site directed α-keto carbonyl inhibitors having the side chain of lysine at P1. Compounds of
Autor:
Shi-Shan Mao, Jules A. Shafer, Neeper Michael P, Jin Huang, Victor M. Garsky, Carolee Welebob
Publikováno v:
Biochemistry. 34:5098-5103
Tick anticoagulant peptide (TAP) is a specific and potent inhibitor of factor Xa (fXa), a central enzyme in the blood clotting cascade. As such, TAP is a potential antithrombotic agent. Site-directed mutagenesis studies were undertaken to determine t