Zobrazeno 1 - 10
of 21
pro vyhledávání: '"Karen L. Milkiewicz"'
Publikováno v:
Organic Process Research & Development. 22:1236-1240
Spiro[1H-pyrido[2,3-d][1,3]oxazine-4,4′-piperidine]-2-one (3) is a key building block in many biologically active compounds. The synthesis of this compound, as reported in the literature, is low-yielding. We have discovered and developed a robust,
Autor:
Christie Michael, James J. Reif, Dale R. Mowrey, Karen L. Milkiewicz, Roger P. Bakale, Mark A. Olsen, Vikram C. Purohit, Shawn P. Allwein, Christopher J. Neville, Gregory J. Gilmartin, Daniel E. Petrillo
Publikováno v:
Organic Process Research & Development. 21:740-747
The development of a scalable route to TEV-37440, a dual inhibitor of focal adhesion kinase (FAK) and anaplastic lymphoma kinase (ALK), is presented. The medicinal chemistry route used to support this target through nomination is reviewed, along with
Autor:
Shawn P. Allwein, Christopher J. Neville, Christie Michael, Karen L. Milkiewicz, Mildred L. Kaufman, Daniel V. Levy, Yi Wang, Nelson G. Landmesser, Linli He, Mark A. Olsen, Kannan Muthukumaran
Publikováno v:
Organic Process Research & Development. 21:408-413
Cinchona alkaloid-based thiourea catalysts (1a and 1b) belong to an important class of bifunctional organocatalysts, which has been widely used for a variety of asymmetric reactions. The commercial availability of these catalysts is sporadic, and lim
Autor:
Linda Weinberg, Ted L. Underiner, Mark S. Albom, Craig A. Zificsak, Arup K. Ghose, Renee C. Roemmele, Mangeng Cheng, Karen L. Milkiewicz, Jay P. Theroff, Bruce D. Dorsey, Thelma S. Angeles
Publikováno v:
Bioorganic & Medicinal Chemistry. 18:4351-4362
Dysregulation of the anaplastic lymphoma kinase (ALK) is implicated in a variety of cancers. A series of tetrahydropyrido[2,3-b]pyrazines was constructed as ring-constrained analogs of a known aminopyridine kinase scaffold. Chemistry was developed to
Autor:
Pierre Raboisson, Raul R. Calvo, Rose Tominovich, Louis V. LaFrance, Karen L. Milkiewicz, Dana L. Johnson, Anna C. Maroney, Shuyuan Zhao, Robert R. Donatelli, Maxwell D. Cummings, Bruce L. Grasberger, Christopher J. Molloy, Tianbao Lu, Juan J. Marugan, Daniel J. Parks, Kristi A. Leonard, Carol F. Franks, Joan Gushue, Holly K. Koblish
Publikováno v:
Molecular Cancer Therapeutics. 5:160-169
The activity and stability of the p53 tumor suppressor are regulated by the human homologue of the mouse double minute 2 (Hdm2) oncoprotein. It has been hypothesized that small molecules disrupting the Hdm2:p53 complex would allow for the activation
Autor:
Jennifer Lattanze, Tianbao Lu, Karen L. Milkiewicz, Bruce L. Grasberger, Theodore E. Carver, Louis V. LaFrance, Daniel J. Parks, Kannan Ramachandren, Varsha Gupta, Raul R. Calvo, Diane M. Maguire, Eugene C. Petrella, Maxwell D. Cummings
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 15:765-770
A library of 1,4-benzodiazepine-2,5-diones was screened for binding to the p53-binding domain of HDM2 using Thermofluor ® , a miniaturized thermal denaturation assay. The hits obtained were shown to bind to HDM2 in the p53-binding pocket using a flu
Discovery and Cocrystal Structure of Benzodiazepinedione HDM2 Antagonists That Activate p53 in Cells
Autor:
Tianbao Lu, Jennifer Lattanze, Ingrid Deckman, Marie Zhang, Bruce L. Grasberger, Carl L. Manthey, and Christopher J. Molloy, John C. Spurlino, Diane M. Maguire, Eugene C. Petrella, Kannan Ramachandren, Holly K. Koblish, Shuyuan Zhao, Bruce E. Tomczuk, Gwendolyn R. Bylebyl, Louis V. LaFrance, Carsten Schubert, Daniel J. Parks, Karen L. Milkiewicz, Carol F. Franks, Theodore E. Carver, Roger F. Bone, Anna C. Maroney, Maxwell D. Cummings, Raul R. Calvo, W. Michael Avondale Pantoliano
Publikováno v:
Journal of Medicinal Chemistry. 48:909-912
HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting its tumor suppressive functions. A miniaturized thermal denaturation assay was used to screen chemical libraries, resulting in the discovery of a novel series of benzodiazepined
Publikováno v:
Tetrahedron Letters. 44:4257-4260
Furan[3,2-b]pyrroles are important isosteres for the indole scaffold in which the benzene ring is replaced by the furan ring. A series of novel tetra-substituted furan[3,2-b]pyrroles was synthesized from a simple furaldehyde. The divergent synthesis
Autor:
Matthew A. Curry, Zeqi Huang, Karen L. Milkiewicz, Benjamin J. Dugan, Pawel Dobrzanski, Bruce D. Dorsey, Eugen F. Mesaros, Bruce Ruggeri, Sheryl L. Meyer, Jennifer L. Mason, Mahfuza Jan, Mark S. Albom, Thelma S. Angeles, Diane E. Gingrich, Mark A. Ator, Allison L. Zulli, Lisa D. Aimone, Cynthia Serdikoff, Kevin J. Wells-Knecht
Publikováno v:
Journal of medicinal chemistry. 55(11)
Members of the JAK family of nonreceptor tyrosine kinases play a critical role in the growth and progression of many cancers and in inflammatory diseases. JAK2 has emerged as a leading therapeutic target for oncology, providing a rationale for the de
Autor:
Henry J. Breslin, James P. Finn, Lisa Saville, Jennifer L. Mason, Ted L. Underiner, Derek Dunn, Linda Weinberg, Jean Husten, Mahfuza Jan, Jay P. Theroff, Thelma S. Angeles, Teresa M. O'Kane, Karen L. Milkiewicz, Diane E. Gingrich, Tho V. Thieu, Lisa D. Aimone, Mark S. Albom, Craig A. Zificsak, Bruce D. Dorsey, Pawel Dobrzanski
Publikováno v:
Bioorganicmedicinal chemistry letters. 22(1)
The elaboration of a novel scaffold for the inhibition of JAK2 and FAK kinases was targeted in order to provide a dual inhibitor that could target divergent pathways for tumor cell progression.