Zobrazeno 1 - 10
of 34
pro vyhledávání: '"Kevin J. Wells-Knecht"'
Autor:
Kevin J. Wells-Knecht, Derek Dunn
Publikováno v:
Journal of Pharmaceutical Sciences. 108:3152-3155
Azo compounds are commonly used to study radical-mediated degradation of pharmaceutical compounds. The favorable chemical and physical properties of 2,2'-azobis(2-methylpropanenitrile) (AIBN) have made it one of the most widely used compound for thes
Autor:
Nathan Anderson, Diane E. Gingrich, Arup K. Ghose, Mark S. Albom, Bruce D. Dorsey, Lisa D. Aimone, Elizabeth Bruckheimer, Jason C. Wagner, Matthew A. Curry, Lihui Lu, Jay Friedman, Mark A. Ator, Bruce Ruggeri, Eugen F. Mesaros, Mangeng Cheng, Zeqi Huang, Keith S. Learn, Matthew R. Quail, Thelma S. Angeles, Pawel Dobrzanski, Gregory R. Ott, Sandra V. Fernandez, Joseph G. Lisko, Kevin J. Wells-Knecht, Weihua Wan
Publikováno v:
Journal of medicinal chemistry. 59(16)
Analogues structurally related to anaplastic lymphoma kinase (ALK) inhibitor 1 were optimized for metabolic stability. The results from this endeavor not only led to improved metabolic stability, pharmacokinetic parameters, and in vitro activity agai
Autor:
Gregory J. Wells, Weihua Wan, Henry J. Breslin, Kevin J. Wells-Knecht, Bruce D. Dorsey, Mark A. Ator, Rabindranath Tripathy, Lisa D. Aimone, Mangeng Cheng, Ashley T. Wohler, Zeqi Huang, Tho V. Thieu, Thelma S. Angeles, Matthew R. Quail, Eugen F. Mesaros, Craig A. Zificsak, James Diebold, Jason C. Wagner, Gregory R. Ott, Lihui Lu, Robert J. McHugh, Mark S. Albom
Publikováno v:
Journal of Medicinal Chemistry. 55:115-125
Chemical strategies to mitigate cytochrome P450-mediated bioactivation of novel 2,7-disubstituted pyrrolo[2,1-f][1,2,4]triazine ALK inhibitors are described along with synthesis and biological activity. Piperidine-derived analogues showing minimal mi
Autor:
Henry J. Breslin, Bruce D. Dorsey, Arup K. Ghose, Mangeng Cheng, Mark S. Albom, Kevin J. Wells-Knecht, Weihua Wan, Thelma S. Angeles, R. Curtis Haltiwanger, Brandon M. Lane, Gregory R. Ott
Publikováno v:
Journal of Medicinal Chemistry. 55:449-464
A novel set of 2,4,8,22-tetraazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaene macrocycles were prepared as potential anaplastic lymphoma kinase (ALK) inhibitors, designed to rigidly lock an energy-minimized bioacti
Autor:
Gregory R. Ott, Linda Weinberg, Henry J. Breslin, Lisa D. Aimone, Diane E. Gingrich, Kevin J. Wells-Knecht, Mark A. Ator, Gregory J. Wells, Mehran Yazdanian, Eugen F. Mesaros, Zeqi Huang, Kelli S. Zeigler, Bruce D. Dorsey, Mangeng Cheng
Publikováno v:
Chemical Research in Toxicology. 24:1994-2003
There are numerous published studies establishing a link between reactive metabolite formation and toxicity of various drugs. Although the correlation between idiosyncratic reactions and reactive metabolite formation is not 1:1, the association betwe
Autor:
Deborah Galinis, Sheila J. Miknyoczki, Ted L. Underiner, Damaris Rolon-Steele, Jean Husten, Craig A. Zificsak, Thelma S. Angeles, Torsten Herbertz, Mark S. Albom, Bruce D. Dorsey, Laura S. Kocsis, Kevin J. Wells-Knecht, Jay P. Theroff, Lisa D. Aimone, Kelli S. Zeigler, Candace S. Worrell, Rebecca A. Brown, Christine LoSardo, Seetha Murthy, Jennifer Grobelny
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 21:660-663
Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number of c-Met inhibitors in which kinase selectivity was modulated by substituents appended on the C4-aminobenzamide ring and the nature of the C2-aminoaryl ring. Further lea
Autor:
David Barrett, Stacey T. Long, Francis X. Tavares, David N. Deaton, Lois L. Wright, Hui-Qiang Q. Zhou, Vicente Samano, John G. Catalano, Kevin J. Wells-Knecht, Aaron B. Miller, Robert B. McFadyen, Larry R. Miller
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 17:22-27
Starting from a potent ketone-based inhibitor with poor drug properties, incorporation of P2–P3 elements from a ketoamide-based inhibitor led to the identification of a hybrid series of ketone-based cathepsin K inhibitors with better oral bioavaila
Autor:
Robert B. McFadyen, Aaron B. Miller, Stacey T. Long, Kevin J. Wells-Knecht, Larry R. Miller, David N. Deaton, David Barrett, John G. Catalano, Lois L. Wright
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 15:2209-2213
Several novel ketoamide-based inhibitors of cathepsin K have been identified. Starting from a modestly potent inhibitor, structural screening of P2 elements led to 100-fold enhancements in inhibitory activity. Modifications to one of these leads resu
Autor:
Kevin J. Wells-Knecht, David Barrett, John G. Catalano, David N. Deaton, Lois L. Wright, Larry R. Miller, Hui-Qiang Q. Zhou, Francis X. Tavares, Stacey T. Long
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 14:2543-2546
An orally available series of ketoamide-based inhibitors of cathepsin K has been identified. Starting from a potent inhibitor with poor oral bioavailability, modifications to P1 and P1′ elements led to enhancements in solubility and permeability. T
Autor:
David N. Deaton, Kevin J. Wells-Knecht, Lois L. Wright, Robert B. McFadyen, Stacey T. Long, Larry R. Miller, J. Alan Payne, John G. Catalano
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 14:719-722
A novel series of ketoamide-based inhibitors of cathepsin K has been identified. Modifications to P(2) and P(3) elements were crucial to enhancing inhibitory activity. Although not optimized, a selected inhibitor was effective in attenuating type I c