Glutarimide

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Glutarimide
Skeletal formula
Ball-and-stick model
Names
Preferred IUPAC name
Piperidine-2,6-dione
Other names
NSC 58190,EINECS 214-340-4,BRN 0110052
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.013.038 Edit this at Wikidata
UNII
  • InChI=1S/C5H7NO2/c7-4-2-1-3-5(8)6-4/h1-3H2,(H,6,7,8)
    Key: KNCYXPMJDCCGSJ-UHFFFAOYSA-N
  • C1CC(=O)NC(=O)C1
Properties
C5H7NO2
Molar mass 113.11 g/mol
Appearance White crystalline powder
Melting point 155-157 °C[1]
Soluble in water, ethanol, acetone
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Glutarimide, also known as piperidine-2,6-dione, is an organic compound with the chemical formula C5H7NO2. It is a white crystalline powder formed by the dehydration of the amide of glutaric acid. Glutarimide serves as a core structural component in several pharmacologically active compounds, including thalidomide, lenalidomide, cycloheximide, and glutethimide, which exhibit immunomodulatory, anticancer, or antibiotic properties.[2] As a standalone compound, glutarimide is used in chemical synthesis and research, with no direct therapeutic applications.[3][4]

The drug lenalidomide contains the substructure glutarimide (blue).

Chemical properties

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Glutarimide is a heterocyclic compound with a six-membered piperidine ring containing two ketone groups at positions 2 and 6, forming a dicarboximide structure.[2] Its molecular formula, C5H7NO2, corresponds to a molecular weight of 113.114 g/mol, with a melting point of 152–154 °C and solubility in water, ethanol, and acetone.[3] It is synthesized by heating glutaric acid with ammonia, followed by dehydration to close the imide ring.[5] N-acyl-glutarimides are key intermediates in N–C(O) cross-coupling reactions due to their destabilized amide bond, enabling applications in organic synthesis.[6]

Pharmacology

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Glutarimide itself lacks direct pharmacological activity but is a critical scaffold in several drugs.[2] Derivatives like thalidomide and lenalidomide bind to cereblon (CRBN), an E3 ubiquitin ligase adaptor, promoting protein degradation and exerting immunomodulatory and anti-angiogenic effects.[5] Cycloheximide inhibits protein synthesis by blocking translation elongation in eukaryotic cells, making it a valuable research tool.[3] Glutarimide antibiotics, such as 9-methylstreptimidone, exhibit antiviral, antitumor, and antifungal activities through protein biosynthesis inhibition.[3] The glutarimide moiety’s interaction with biological targets underpins its pharmacological versatility.[5]

History

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Glutarimide was first synthesized in the early 20th century from glutaric acid, initially valued for its synthetic utility.[5] Its pharmacological relevance emerged with thalidomide in the 1950s, marketed as a sedative but withdrawn in 1961 after causing thousands of birth defects.[5] Thalidomide’s reapproval in 1998 for ENL and later for multiple myeloma led to the development of safer IMiDs like lenalidomide.[5] Glutarimide remains a key scaffold in modern drug design, particularly for CRBN-targeted therapies.[6]

See also

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References

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  1. ^ Glutarimide - Sigma-Aldrich
  2. ^ a b c "Glutarimide". PubChem. Retrieved 17 June 2025.
  3. ^ a b c d "Glutarimide". ChemicalBook. Retrieved 17 June 2025.
  4. ^ Paris, G.; Berlinguet, L.; Gaudry, R.; English, Jr., J.; Dayan, J. E. (1957). "Glutaric Acid and Glutarimide". Organic Syntheses. 37: 47. doi:10.15227/orgsyn.037.0047.
  5. ^ a b c d e f Burgers, Luisa D.; Fürst, Robert (August 2021). "Natural products as drugs and tools for influencing core processes of eukaryotic mRNA translation". Pharmacological Research. 170 105535. doi:10.1016/j.phrs.2021.105535. PMID 34058326.
  6. ^ a b Hei, Xiuze; Liu, Wei; Zhu, Kun; Teat, Simon J.; Jensen, Stephanie; Li, Mingxing; O’Carroll, Deirdre M.; Wei, Kevin; Tan, Kui; Cotlet, Mircea; Thonhauser, Timo; Li, Jing (4 March 2020). "Blending Ionic and Coordinate Bonds in Hybrid Semiconductor Materials: A General Approach toward Robust and Solution-Processable Covalent/Coordinate Network Structures". Journal of the American Chemical Society. 142 (9): 4242–4253. Bibcode:2020JAChS.142.4242H. doi:10.1021/jacs.9b13772. PMID 32045231.