Indoprofen

Last updated
Indoprofen
Indoprofen.svg
Clinical data
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • Withdrawn
Pharmacokinetic data
Bioavailability High (rapid and complete absorption)
Metabolism Glucuronidation
Elimination half-life 2.3 hours
Excretion Renal
Identifiers
  • 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 InfoCard 100.046.197 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C17H15NO3
Molar mass 281.311 g·mol−1
3D model (JSmol)
  • O=C(O)C(c1ccc(cc1)N3C(=O)c2ccccc2C3)C
  • 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) Yes check.svgY
  • Key:RJMIEHBSYVWVIN-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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 It was withdrawn worldwide in the 1980s after postmarketing reports of severe gastrointestinal bleeding.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

Contents

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.

ChemDrug Synthesis: Patents: Indoprofen synthesis.svg
ChemDrug Synthesis: Patents:

The nitro group in p-nitro-hydratropic acid [19910-33-9] (1) is reduced to give 4-aminohydratropic acid [59430-62-5] (2). Further reaction with phthalic anhydride [85-44-9] gave [59430-61-4] (4). Treatment of the new imide with zinc in acetic acid leads, interestingly to reduction of but one of the carbonyl groups to afford indolone (5).

See also

Related Research Articles

<span class="mw-page-title-main">Ibuprofen</span> Medication treating pain, fever, and inflammation

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be used orally or intravenously. It typically begins working within an hour.

<span class="mw-page-title-main">Spinal muscular atrophies</span> Group of disorders

Spinal muscular atrophies (SMAs) are a genetically and clinically heterogeneous group of rare debilitating disorders characterised by the degeneration of lower motor neurons and subsequent atrophy (wasting) of various muscle groups in the body. While some SMAs lead to early infant death, other diseases of this group permit normal adult life with only mild weakness.

<span class="mw-page-title-main">Progressive muscular atrophy</span> Medical condition

Progressive muscular atrophy (PMA), also called Duchenne–Aran disease and Duchenne–Aran muscular atrophy, is a disorder characterised by the degeneration of lower motor neurons, resulting in generalised, progressive loss of muscle function.

<span class="mw-page-title-main">Spinal muscular atrophy</span> Rare congenital neuromuscular disorder

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is usually diagnosed in infancy or early childhood and if left untreated it is the most common genetic cause of infant death. It may also appear later in life and then have a milder course of the disease. The common feature is progressive weakness of voluntary muscles, with arm, leg and respiratory muscles being affected first. Associated problems may include poor head control, difficulties swallowing, scoliosis, and joint contractures.

Gideon Dreyfuss is an American biochemist, the Isaac Norris Professor of Biochemistry and Biophysics at the University of Pennsylvania School of Medicine, and an investigator of the Howard Hughes Medical Institute. He was elected to the National Academy of Sciences in 2012.

<span class="mw-page-title-main">Flunarizine</span> Calcium channel blocker medication

Flunarizine, sold under the brand name Sibelium among others, is a drug classified as a calcium antagonist which is used for various indications. It is not available by prescription in the United States or Japan. The drug was discovered at Janssen Pharmaceutica (R14950) in 1968.

<span class="mw-page-title-main">Survival of motor neuron</span> Protein in animal cells

Survival of motor neuron or survival motor neuron (SMN) is a protein that in humans is encoded by the SMN1 and SMN2 genes.

<i>SMN1</i> Protein-coding gene in the species Homo sapiens

Survival of motor neuron 1 (SMN1), also known as component of gems 1 or GEMIN1, is a gene that encodes the SMN protein in humans.

<span class="mw-page-title-main">Small nuclear ribonucleoprotein D2</span> Protein-coding gene in the species Homo sapiens

Small nuclear ribonucleoprotein Sm D2 is a protein that in humans is encoded by the SNRPD2 gene. It belongs to the small nuclear ribonucleoprotein core protein family, and is required for pre-mRNA splicing and small nuclear ribonucleoprotein biogenesis. Alternative splicing occurs at this locus and two transcript variants encoding the same protein have been identified.

<span class="mw-page-title-main">Gem-associated protein 2</span> Protein-coding gene in the species Homo sapiens

Gem-associated protein 2 (GEMIN2), also called survival of motor neuron protein-interacting protein 1 (SIP1), is a protein that in humans is encoded by the GEMIN2 gene.

<span class="mw-page-title-main">DDX20</span> Protein-coding gene in the species Homo sapiens

Probable ATP-dependent RNA helicase DDX20, also known as DEAD-box helicase 20 and gem-associated protein 3 (GEMIN3), is an enzyme that in humans is encoded by the DDX20 gene.

<span class="mw-page-title-main">NAIP (gene)</span> Protein and coding gene in humans

Baculoviral IAP repeat-containing protein 1 is a protein that in humans is encoded by the NAIP gene.

<span class="mw-page-title-main">CHODL</span> Protein-coding gene in the species Homo sapiens

Chondrolectin is a protein that in humans is encoded by the CHODL gene. Mouse chondrolectin is encoded by Chodl.

<span class="mw-page-title-main">ALS</span> Rare neurodegenerative disease

Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's disease in the United States, is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and lower motor neurons that normally control voluntary muscle contraction. ALS is the most common form of the motor neuron diseases. ALS often presents in its early stages with gradual muscle stiffness, twitches, weakness, and wasting. Motor neuron loss typically continues until the abilities to eat, speak, move, and, lastly, breathe are all lost. While only 15% of people with ALS also fully develop frontotemporal dementia, an estimated 50% face at least some minor difficulties with thinking and behavior. Depending on which of the aforementioned symptoms develops first, ALS is classified as limb-onset or bulbar-onset.

<i>SMN2</i> Protein-coding gene in the species Homo sapiens

Survival of motor neuron 2 (SMN2) is a gene that encodes the SMN protein in humans.

Congenital distal spinal muscular atrophy (cDSMA), also known as distal hereditary motor neuropathytype VIII (dHMN8), is a hereditary medical condition characterized by muscle wasting (atrophy), particularly of distal muscles in legs and hands, and by early-onset contractures of the hip, knee, and ankle. Affected individuals often have shorter lower limbs relative to the trunk and upper limbs. The condition is a result of a loss of anterior horn cells localized to lumbar and cervical regions of the spinal cord early in infancy, which in turn is caused by a mutation of the TRPV4 gene. The disorder is inherited in an autosomal dominant manner. Arm muscle and function, as well as cardiac and respiratory functions are typically well preserved.

<span class="mw-page-title-main">Epigenetics of neurodegenerative diseases</span> Field of study

Neurodegenerative diseases are a heterogeneous group of complex disorders linked by the degeneration of neurons in either the peripheral nervous system or the central nervous system. Their underlying causes are extremely variable and complicated by various genetic and/or environmental factors. These diseases cause progressive deterioration of the neuron resulting in decreased signal transduction and in some cases even neuronal death. Peripheral nervous system diseases may be further categorized by the type of nerve cell affected by the disorder. Effective treatment of these diseases is often prevented by lack of understanding of the underlying molecular and genetic pathology. Epigenetic therapy is being investigated as a method of correcting the expression levels of misregulated genes in neurodegenerative diseases.

<span class="mw-page-title-main">Nusinersen</span> Medication used for spinal muscular atrophy

Nusinersen, marketed as Spinraza, is a medication used in treating spinal muscular atrophy (SMA), a rare neuromuscular disorder. In December 2016, it became the first approved drug used in treating this disorder.

<span class="mw-page-title-main">Branaplam</span> Chemical compound

Branaplam is a pyridazine derivative that is being studied as an experimental drug. It was originally developed by Novartis to treat spinal muscular atrophy (SMA); since 2020 it was being developed to treat Huntington's disease but the trial ended in 2023 due to toxicity concerns.

<span class="mw-page-title-main">Risdiplam</span> Chemical compound

Risdiplam, sold under the brand name Evrysdi, is a medication used to treat spinal muscular atrophy (SMA) and the first oral medication approved to treat this disease.

References

  1. 1 2 Frazin N (March 9, 2005). "Pain Reliever May Provide Clues for Treating Spinal Muscular Atrophy". United States National Institute of Neurological Disorders and Stroke. Archived from the original on 2008-07-04. 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. Castaer, J.; Arrigoni, Martelli, E.; Indoprofen. Drugs Fut 1976, 1, 5, 242.
  4. 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.
  5. BE 753600 ; Carney RW, de Stevens G U.S. patent 4,316,850 (1970, 1982 both to Ciba).
  6. Giraldi PN, et al., DE 2154525 (1972 to Carlo Erba), C.A. 77, 88292v (1972).