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| Names | |||
|---|---|---|---|
| Preferred IUPAC name Piperidine-2,6-dione | |||
| Other names 2,6-Piperidine-dione; NSC 58190; BRN 0110052 | |||
| Identifiers | |||
3D model (JSmol) | |||
| ChemSpider | |||
| ECHA InfoCard | 100.013.038 | ||
| EC Number |
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| UNII | |||
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| Properties | |||
| C5H7NO2 | |||
| Molar mass | 113.116 g·mol−1 | ||
| Appearance | White crystalline powder | ||
| Melting point | 155–157 °C (311–315 °F; 428–430 K)[1] | ||
| Soluble in water, ethanol, acetone | |||
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |||
Glutarimide, also known aspiperidine-2,6-dione, is an organic compound with the chemical formulaC5H7NO2. 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, includingthalidomide,lenalidomide,cycloheximide, andglutethimide, 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]
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]
Glutarimide itself lacks direct pharmacological activity but is a critical scaffold in several drugs.[2] Derivatives like thalidomide and lenalidomide bind tocereblon (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]
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]
