Zobrazeno 1 - 10
of 26
pro vyhledávání: '"S. Dale Lewis"'
Autor:
Vanessa L. Sherman, M. Reza Anari, Catherine M. Wiscount, Julie A. Krueger, Christopher J. Kochansky, Bobby J. Lucas, Tran Lekhanh O, Joseph P. Vacca, Terry A. Lyle, Bradley K. Wong, Sanderson Philip E, Heidi L. Shimp, Peter D. Williams, Sean Yu, Donnette D. Staas, Kelly L. Savage, S. Dale Lewis, Rebecca B. White, Youwei Yan, Daniel R. McMasters
Publikováno v:
Bioorganic & Medicinal Chemistry. 14:6900-6916
Previous reports from our laboratories described potent tripeptide thrombin inhibitors which incorporate heterocycle-substituted chlorophenyl groups in the P1 position. Using these as lead compounds for further optimization, we identified sites of me
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:
Rebecca B. White, Bradley K. Wong, Elizabeth A. Lyle, K.J. Stauffer, Matthew M. Morrissette, S. Dale Lewis, Joseph P. Vacca, Yvonne M. Leonard, Cynthia Miller-Stein, Audrey A. Wallace, Bobby J. Lucas, Daniel R. McMasters, Julie A. Krueger, Joseph J. Lynch, Terry A. Lyle, Denise C. Welsh, Peter D. Williams
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 14:4161-4164
Modification of lead compound 1 by reducing lipophilicity in the P3 group produced a series of low molecular weight thrombin inhibitors with excellent potency in functional assays, metabolic stability, and oral bioavailability. These modifications le
Autor:
Philippe G. Nantermet, Harold G. Selnick, Youwei Yan, Bobby J. Lucas, Janetta M. Pellicore, Joseph P. Vacca, Julie A. Krueger, James C. Barrow, Christina L. Newton, S. Dale Lewis, Mary Beth Young, Lawrence C. Kuo, Daniel R. McMasters
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 13:2781-2784
A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin
Autor:
Dennis L. Bohn, Sanderson Philip E, Bobby J. Lucas, Adel M. Naylor-Olsen, Julie A. Krueger, Elizabeth A. Lyle, Franklin C. Clayton, Youwei Yan, S. Dale Lewis, Denise J. Bickel, Denice C. Welsh, Kellie J. Cutrona, Audrey A. Wallace, Kelly L. Savage
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 13:1441-1444
We describe a series of highly potent and efficacious thrombin inhibitors based on a 3-amino-4-sulfonylpyridinone acetamide template. The functionally dense sulfonyl group stabilizes the aminopyridinone, conformationally constrains the 4-substituent,
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
Autor:
Diane M Rush, Jillian M Di Muzio-Mower, Carl F. Homnick, Elizabeth A. Lyle, I.-W. Chen, Marylou Juliano, Julie A. Krueger, Kari Vastag, Joseph P. Vacca, Bobby J. Lucas, Craig A. Coburn, Peter D. Williams, S. Dale Lewis
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 10:1069-1072
A new class of conformationally constrained thrombin inhibitors is described. These compounds contain a unique bicyclic pyridone scaffold which serves as a P3P2 dipeptide surrogate. The synthesis and antithrombotic activity of these inhibitors is rep
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:
John J. Baldwin, S. Dale Lewis, D. Dumas, Adel M. Naylor-Olsen, Gérard Leclerc, Murcko Mark A
Publikováno v:
European Journal of Medicinal Chemistry. 33:471-488
Thrombin plays a central role in thrombosis. Because of the medical need for novel antithrombotic drugs, a search for structurally novel thrombin inhibitors was undertaken. In the absence of a crystal structure, a class was designed based on a modeli