Glutarimide

Glutarimide is the cyclic imide derived from glutaric acid. Chemically, it is a six-membered lactam (piperidin-2,6-dione) consisting of a piperidine ring with two carbonyl groups at positions 2 and 6.

Preparation of the parent compound can be achieved by intramolecular cyclization of glutaric acid derivatives. In practice, glutaric anhydride or related diacids can react with ammonia or ammonium salts to form the imide, a reaction generally described as lactamization or ring-closure to give glutarimide. The compound is available commercially and can serve as a versatile building block in organic synthesis.

Glutarimide is notable in medicinal chemistry as the core motif of immunomodulatory imide drugs (IMiDs). The glutarimide moiety is present in thalidomide and its more potent analogs, lenalidomide and pomalidomide. These drugs bind to the cereblon E3 ubiquitin ligase, altering substrate degradation and producing immunomodulatory, anti-angiogenic, and anti-proliferative effects that underpin their clinical uses in cancer and inflammatory diseases.

Aside from pharmaceuticals, glutarimide and its derivatives are used as synthetic scaffolds in organic chemistry and appear in various natural products and agrochemical leads.