Indoprofen

Indoprofen

Systematic (IUPAC) name
2-[4-(1-oxo-1,3-dihydro-2H-isoindol-2-yl) phenyl]propanoic acid
Clinical data
Routes of administration	Oral
Legal status
Legal status	Withdrawn
Pharmacokinetic data
Bioavailability	High (rapid and complete absorption)
Metabolism	Glucuronidation
Biological half-life	2.3 hours
Excretion	Renal
Identifiers
CAS Number	31842-01-0
ATC code	M01AE10 (WHO)
PubChem	CID 3718
DrugBank	DB08951
ChemSpider	3587
UNII	CPE46ZU14N
KEGG	D04530
ChEBI	CHEBI:76162
ChEMBL	CHEMBL15870
Chemical data
Formula	C17H15NO3
Molar mass	281.306 g/mol
SMILES O=C(O)C(c1ccc(cc1)N3C(=O)c2ccccc2C3)C
InChI InChI=1S/C17H15NO3/c1-11(17(20)21)12-6-8-14(9-7-12)18-10-13-4-2-3-5-15(13)16(18)19/h2-9,11H,10H2,1H3,(H,20,21) Key:RJMIEHBSYVWVIN-UHFFFAOYSA-N
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Indoprofen is a non-steroidal anti-inflammatory drug. It was withdrawn worldwide in the 1980s after postmarketing reports of severe gastrointestinal bleeding.^[1]

A 2004 study using high-throughput screening found indoprofen to increase production of the survival of motor neuron protein, suggesting it may provide insight into treatments for spinal muscular atrophies.^[1][2]

Synthesis

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

Indoprofen synthesis:^[3] Patents:^[4][5]

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 (ie. phthalimide) gives the product (4) in which the aniline nitrogen has exchanged with ammonia (apparently phthalic anhydride was not used directly). Treatment of the new imide with zinc in acetic acid leads, interestingly to reduction of but one of the carbonyl groups to afford indolone, indoprofen.

References

1. Frazin, Natalie (March 9, 2005). "Pain Reliever May Provide Clues for Treating Spinal Muscular Atrophy". United States National Institute of Neurological Disorders and Stroke. Retrieved 2007-10-06.
2. Lunn MR, Root DE, Martino AM, et al. (2004). "Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism". Chem Biol 11 (11): 1489–1493. doi:10.1016/j.chembiol.2004.08.024. PMC 3160629. PMID 15555999.
3. Nannini, G; Giraldi, P. N.; Molgora, G; Biasoli, G; Spinelli, F; Logemann, W; Dradi, E; Zanni, G; Buttinoni, A; Tommasini, R (1973). "New analgesic-anti-inflammatory drugs. 1-Oxo-2-substituted isoindoline derivatives". Arzneimittel-Forschung 23 (8): 1090–100. PMID 4801034.
4. BE 753600 ; R. W. J. Carney, G. de Stevens, U.S. Patent 4,316,850 (1970, 1982 both to Ciba).
5. P. N. Giraldi et al., DE 2154525  (1972 to Carlo Erba), C.A. 77, 88292v (1972).