Indoprofen

Indoprofen is a nonsteroidal anti-inflammatory drug (NSAID). It was withdrawn worldwide in the 1980s after postmarketing reports of severe gastrointestinal bleeding.[1]

Indoprofen
Clinical data
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • Withdrawn
Pharmacokinetic data
BioavailabilityHigh (rapid and complete absorption)
MetabolismGlucuronidation
Elimination half-life2.3 hours
ExcretionRenal
Identifiers
IUPAC name
  • 2-[4-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)
    phenyl]propanoic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.046.197
Chemical and physical data
FormulaC17H15NO3
Molar mass281.311 g·mol−1
3D model (JSmol)
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) Y
  • Key:RJMIEHBSYVWVIN-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

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 (i.e. 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 to reduction of but one of the carbonyl groups to afford indolone, indoprofen.

References
  1. Frazin N (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, Flaherty SP, Kelley BP, Coovert DD, et al. (November 2004). "Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism". Chemistry & Biology. 11 (11): 1489–93. doi:10.1016/j.chembiol.2004.08.024. PMC 3160629. PMID 15555999.
  3. Nannini G, Giraldi PN, Molgora G, Biasoli G, Spinelli F, Logemann W, et al. (August 1973). "New analgesic-anti-inflammatory drugs. 1-Oxo-2-substituted isoindoline derivatives". Arzneimittel-Forschung. 23 (8): 1090–100. doi:10.1002/chin.197344288. PMID 4801034.
  4. BE 753600; Carney RW, de Stevens G U.S. Patent 4,316,850 (1970, 1982 both to Ciba).
  5. Giraldi PN, et al., DE 2154525 (1972 to Carlo Erba), C.A. 77, 88292v (1972).
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