- Substituted pyridine and pyrimidine derivatives and their use in treating viral infections
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The present invention provides compounds of Formula (I): and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein each of R, R1, X, Y, Z, R2, R3, R4, R5, R6, R7, R8, R9, R18, R19 and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders.
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Page/Page column 113; 114; 115; 116
(2016/09/26)
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- Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors
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Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.
- Medina, Jesús R.,Becker, Christopher J.,Blackledge, Charles W.,Duquenne, Celine,Feng, Yanhong,Grant, Seth W.,Heerding, Dirk,Li, William H.,Miller, William H.,Romeril, Stuart P.,Scherzer, Daryl,Shu, Arthur,Bobko, Mark A.,Chadderton, Antony R.,Dumble, Melissa,Gardiner, Christine M.,Gilbert, Seth,Liu, Qi,Rabindran, Sridhar K.,Sudakin, Valery,Xiang, Hong,Brady, Pat G.,Campobasso, Nino,Ward, Paris,Axten, Jeffrey M.
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experimental part
p. 1871 - 1895
(2011/05/30)
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- CHEMICAL COMPOUNDS
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The invention is directed to 6-(4-pyι?midinyl)-1 H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R1 - R4 are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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Page/Page column 189-190
(2010/07/10)
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- SUBSTITUTED PYRIDINE AND PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS
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The present invention provides compounds of Formula (I): and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein wherein each of R, R1, X, Y, Z, R2, R3, R4, R5, R6, R7, R8, R9, R18, R19 and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders.
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Page/Page column 147
(2010/04/03)
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- NOVEL SEH INHIBITORS AND THEIR USE
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The invention is directed to novel sEH inhibitors and their use in the treatment of diseases mediated by the sEH enzyme.
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Page/Page column 66-67
(2008/12/07)
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- Pyrimidines and uses thereof
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The invention relates to pyrimidines and uses thereof, including to inhibit lysophosphatidic acid acyltransferase β (LPAAT-β) activity and/or proliferation of cells such as tumor-cells.
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- Simplified analogues of acyclonucleosides. Synthesis of 6-[N-alkyl-N-(4- hydroxybutyl)amino]pyrimidine derivatives
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The synthesis of some 6-alkylaminopyrimidine derivatives bearing a 4- hydroxybutyl chain as sugar mimic is described. These new compounds can be regarded as simplified, ring-opened analogues of purine acyclonucleosides.
- Botta,Saladino,Anzini,Corelli
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p. 1769 - 1777
(2007/10/02)
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- Endowed with anti-viral activity 2-alkylamino-4,6-dihalo pyrimidines
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The invention relates to new pyrimidine derivatives endowed with anti-viral activity, to the method for the preparation thereof and to the pharmaceutical compositions containing them. Pyrimidine derivatives of the invention are useful for the treatment of animals and human patients infected with viruses.
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