Synthesis and rational design of anti-inflammatory compounds: N-phenyl-cyclohexenyl sulfonamide derivatives

The synthesis of (±)‐ethyl 6‐[N‐(2‐chloro‐4‐fluorophenyl)sulfamoyl]cyclohex‐1‐ene‐1‐carboxylate (5n) has been reproduced from a method previously described and served as the background for the preparation of a nitro derivative, potentially useful as an anti‐inflammatory agent. Furthermore, a structure‐based QSAR analysis of a series of N‐arylsulfamoyl congeners derived a highly predictive model for the activities of novel small‐molecule inhibitors of NO and cytokine production, whose preparation may be successfully achieved according to a similar procedure as above. Copyright © 2009 John Wiley & Sons, Ltd. The synthesis of (±)‐ethyl 6‐[N‐(3‐nitrophenyl)sulfamoyl]cyclohex‐1‐ene‐1‐carboxylate, an analog of TAK‐242, was achieved. A MIA‐QSAR model, which is based on a series of TAK‐242 derivatives, was then built and a highly predictive model was produced.