Indoprofen is a nonsteroidal anti-inflammatory drug (NSAID). It was withdrawn worldwide in the 1980s after postmarketing reports of severe

gastrointestinal bleeding Gastrointestinal bleeding (GI bleed), also called gastrointestinal hemorrhage (GIB), is all forms of bleeding in the gastrointestinal tract, from the mouth to the rectum. When there is significant blood loss over a short time, symptoms may include ...

. A 2004 study using

high-throughput screening High-throughput screening (HTS) is a method for scientific experimentation especially used in drug discovery and relevant to the fields of biology, materials science and chemistry. Using robotics, data processing/control software, liquid handling ...

found indoprofen to increase production of the

survival of motor neuron Survival of motor neuron or survival motor neuron (SMN) is a protein that in humans is encoded by the '' SMN1'' and '' SMN2'' genes. SMN is found in the cytoplasm of all animal cells and also in the nuclear gems. It functions in transcriptional r ...

protein, suggesting it may provide insight into treatments for

spinal muscular atrophies Spinal muscular atrophies (SMAs) are a genetically and clinically heterogeneous group of rare debilitating disorders characterised by the degeneration of lower motor neurons (neuronal cells situated in the anterior horn of the spinal cord) and ...

Synthesis

The isoindolone ring system forms the nucleus for one of the more traditional "

profen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus a ...

" NSAIDs.

Reduction of the nitro group in arylpropionic acid (1) gives the corresponding aniline (2). Reaction of the intermediate with the imide (3) from

phthalic anhydride Phthalic anhydride is the organic compound with the formula C6H4(CO)2O. It is the anhydride of phthalic acid. Phthalic anhydride is a principal commercial form of phthalic acid. It was the first anhydride of a dicarboxylic acid to be used commer ...

(i.e.

phthalimide Phthalimide is the organic compound with the formula C6H4(CO)2NH. It is the imide derivative of phthalic anhydride. It is a sublimable white solid that is slightly soluble in water but more so upon addition of base. It is used as a precursor ...

) gives the product (4) in which the aniline nitrogen has exchanged with ammonia (apparently

was not used directly). Treatment of the new imide with zinc in acetic acid leads to reduction of but one of the carbonyl groups to afford indolone, indoprofen.

References

Nonsteroidal anti-inflammatory drugs Withdrawn drugs Isoindolines Lactams Propionic acids {{musculoskeletal-drug-stub