212628-45-0Relevant articles and documents
2-Alkylamino- and alkoxy-substituted 2-amino-1,3,4-oxadiazoles-O-Alkyl benzohydroxamate esters replacements retain the desired inhibition and selectivity against MEK (MAP ERK kinase)
Warmus, Joseph S.,Flamme, Cathlin,Zhang, Lu Yan,Barrett, Stephen,Bridges, Alexander,Chen, Huifen,Gowan, Richard,Kaufman, Michael,Sebolt-Leopold, Judy,Leopold, Wilbur,Merriman, Ronald,Ohren, Jeffrey,Pavlovsky, Alexander,Przybranowski, Sally,Tecle, Haile,Valik, Heather,Whitehead, Christopher,Zhang, Erli
scheme or table, p. 6171 - 6174 (2009/07/18)
This paper reports a second generation MEK inhibitor. The previously reported potent and efficacious MEK inhibitor, PD-184352 (CI-1040), contains an integral hydroxamate moiety. This compound suffered from less than ideal solubility and metabolic stabilit
The discovery of the benzhydroxamate MEK inhibitors CI-1040 and 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
scheme or table, p. 6501 - 6504 (2009/10/01)
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.
Treatment of asthma with MEK inhibitors
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, (2008/06/13)
This invention provides a method of preventing or treating asthma by administering to a patient in need of treatment an effective amount of a selective MEK inhibitor, especially a phenyl amine of Formula I and II:
Method for making 2-(N-phenylamino)benzoic acids
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Page column 4-5, (2010/11/30)
The present invention relates to a method for making 2-N-phenylamino)benzoic acids by coupling a benzoic acid and an aniline using an alkaline metal hexamethyldisilazide as a base.
A simple and efficient synthesis of 2-(N-phenylamino)-benzoic acids
Chen,Beylin,Iakovleva,Kesten,Magano,Vrieze
, p. 411 - 417 (2007/10/03)
A new method for the synthesis of 2-(N-phenylamino)benzoic acids is presented, with 2-fluorobenzoic acids and anilines as starting materials. Several experimental conditions as well as the factors influencing the outcome of the reaction are described.
2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives and their use as MEK inhibitors
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, (2008/06/13)
Phenylamino benzoic acid, benzamides, and benzyl alcohol derivatives of the formula where R1, R2, R3, R4, R5, and R6are hydrogen or substituent groups such as alkyl, and where R7
