1226784-85-5

Upstream product

• 1084332-21-7 2-(3-amino-phenoxy)-4-fluoro-6-(2-fluoro-4-iodo-phenylamino)-benzamide 
• 594-44-5 Ethanesulfonyl chloride 
• 96606-37-0 2,4,6-trifluorobenzonitrile 
• 19962-06-2 tert-butyl 3-hydroxyphenylcarbamate 
• 1192454-69-5 [3-(3-tert-butoxycarbonylamino-phenoxy)-2-cyano-5-fluoro-phenyl]-(2-fluoro-4-iodo-phenyl)-carbamic acid tert-butyl ester 
• 1084333-50-5 2-(2-cyano-3,5-difluoro-phenyl)-(2-fluoro-4-iodo-phenyl)-carbamic acid tert-butyl ester 
• 1084333-49-2 2,4-difluoro-6-(2-fluoro-4-iodo-phenylamino)-benzonitrile 
• 1297594-71-8 C₁₃H₈F₃IN₂O 
• 29632-74-4 2-fluro-4-iodoaniline 
• 82019-50-9 2,4,6-trifluorobenzamide 

Relevant academic research and scientific papers

Optimization of allosteric MEK inhibitors. Part 1: Venturing into underexplored SAR territories

Using PD325901 as a starting point for identifying novel allosteric MEK inhibitors with high cell potency and long-lasting target inhibition in vivo, truncation of its hydroxamic ester headgroup was combined with incorporation of alkyl and aryl ethers at the neighboring ring position. Whereas alkoxy side chains did not yield sufficient levels of cell potency, specifically substituted aryloxy groups allowed for high enzymatic and cellular potencies. Sulfamide 28 was identified as a highly potent MEK inhibitor with nanomolar cell potency against B-RAF (V600E) as well as Ras-mutated cell lines, high metabolic stability and resulting long half-lives. It was efficacious against B-RAF as well as K-Ras driven xenograft models and showed - despite being orally bioavailable and not a P-glycoprotein substrate - much lower brain/plasma exposure ratios than PD325901.

SUBSTITUTED SULPHONAMIDO PHENOXYBENZAMIDES

The present invention relates to substituted sulphonamido phenoxybenzamide compounds of general formula (I) in which A, R1, R2, R3, R4, R5, R6, R7, R8 and n are as defined in the claims, to pharmaceutical compositions and combinations containaining said compounds, to methods of preparing said compounds, and to the use of said compounds or compositions for treating hyper- proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients.