Design and synthesis of some isoindoline derivatives as analogues of the active anti-inflammatory Indoprofen

Abstract

Searching new targets for anti-inflammatory drug design, agents with the isoindole skeleton were focused on the basis of preliminary studies of NSAIDs as COX-1 and/or COX-2 enzyme inhibitors. Thus several novel N-substituted isoindoline derivatives as possible biologically active compounds were prepared as analogues of Indoprofen (1) starting from cis-2- [(4-methylphenyl)carbonyl]cyclohexanecarboxylic acid (3) by treatment with primary arylamines.

Merging C–H Activation and Strain–Release in Ruthenium-Catalyzed Isoindolinone Synthesis

“…According to our ongoing efforts in catalytic transformation of benzoic acids and heterocycle synthesis, we believe that the rational combination of metal catalyst and solvent may provide a solution to the aforementioned problems. In should be noted that isoindolinones are widely found in natural products and bioactive molecules (Scheme c) . The established methods mainly rely on the use of stoichiometric oxidants, high temperatures (>200 °C), and specialized N -directing groups .…”

Copper-Catalyzed sp3 C–H Aminative Cyclization of 2-Alkyl-N-arylbenzamides: An Approach for the Synthesis of N-Aryl-isoindolinones

“…Isoindolinones with sp 3 C–N bonds are found in many natural and synthetic drug molecules, for example, indoprofen (an anti-inflammatory), stachybotrin (an anxiolytic), and staurosporine (a protein kinase C inhibitor) (Figure ). Many methods have been reported for the synthesis of N -substituted isoindolinones, such as selective monoreduction of phthalimides, transition-metal-catalyzed cyclization of 2-halobenzamides, olefination of benzoic amides, and Pd-catalyzed cycloamino­carbonylation .…”

Efficient syntheses of substituted (±)-3-oxoisoindoline-1-carbonitriles and carboxamides using OSU-6

“…14 The commercial drug indoprofen, which was used as an anti-inflammatory agent in the 1970s, contains an isoindolinone ring in its core structure. 15,16 Apart from their bioactivity, these heterocycles also find utility as molecular switches due to their electrochemical properties. 17 Despite their potential medicinal and electrochemical applications, relatively few approaches exist for the preparation of isoindolinone rings and these generally require multistep syntheses or expensive metal catalysts.…”