- 5-Carboxyfluorescein tagged N-phenylanthranilamide as a tracer reagent for fluorescence polarization: A robust method to screen MAPK pathway allosteric inhibitors
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Fluorescence polarization using Nα-(fluorescein-5- carbonyl)-Nε-(N-[2-fluoro-4-iodophenyl]-3,4- difluoroanthraniloyl)lysyl amide is capable of rapidly identifying inhibitor ligands that bind to an allosteric site in MEK1. The Royal Society of Chemistry.
- Rezvani, Z. Nooshin,Mayer, R. John,Chan, Weng C.
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supporting information; experimental part
p. 2043 - 2045
(2010/09/05)
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- The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901
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A novel series of benzhydroxamate esters derived from their precursor anthranilic acids have been prepared and have been identified as potent MEK inhibitors. 2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzam ide, CI-1040, was the first MEK inhibitor to demonstrate in vivo activity in preclinical animal models and subsequently became the first MEK inhibitor to enter clinical trial. CI-1040 suffered however from poor exposure due to its poor solubility and rapid clearance, and as a result, development of the compound was terminated. Optimization of the diphenylamine core and modification of the hydroxamate side chain for cell potency, solubility, and exposure with oral delivery resulted in the discovery of the clinical candidate N-(2,3-dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-b enzamide PD 0325901.
- Barrett, Stephen D.,Bridges, Alexander J.,Dudley, David T.,Saltiel, Alan R.,Fergus, James H.,Flamme, Cathlin M.,Delaney, Amy M.,Kaufman, Michael,LePage, Sophie,Leopold, Wilbur R.,Przybranowski, Sally A.,Sebolt-Leopold, Judith,Van Becelaere, Keri,Doherty, Annette M.,Kennedy, Robert M.,Marston, Dan,Howard Jr., W. Allen,Smith, Yvonne,Warmus, Joseph S.,Tecle, Haile
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scheme or table
p. 6501 - 6504
(2009/10/01)
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- 5-SUBSTITUTED-2-PHENYLAMINO-BENZAMIDE AS MEK INHIBITOR
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An objective of the present invention is to provide compounds that exhibit strong MEK-inhibiting activity and are stable in vivo and soluble in water, which can be used as preventive or therapeutic agents for proliferative diseases. The compounds of the present invention and pharmaceutically acceptable salts thereof are represented by the following formula (1): [where R1, R2, R3, R4, and X are the same as defined in the present patent application].
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Page/Page column 149
(2008/06/13)
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- Oxygenated esters of 4-lodo phenylamino benzhydroxamic acids
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The present invention relates to oxygenated esters of 4-iodophenylamino benzhydroxamic acid derivatives, pharmaceutical compositions and methods of use thereof. The present invention also relates to crystaline forms of oxygenated esters of 4-iodophenylamino benzhydroxamic acid derivatives, pharmaceutical compositions and methods of use thereof.
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- N-(4-substituted phenyl)-anthranilic acid hydroxamate esters
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The present invention relates to oxygenated esters of 4-substituted-phenylamino benzhydroxamic acid derivatives, pharmaceutical compositions and methods of use thereof.
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