9255. Thalidomide

Nomenclature

CAS number: 50-35-1
2-(2,6-Dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione; N-(2,6-dioxo-3-piperidyl)phthalimide; α-phthalimidoglutarimide; 3-phthalimidoglutarimide; 2,6-dioxo-3-phthalimidopiperidine; N-phthalylglutamic acid imide; N-phthaloylglutamimide; K-17; Contergan; Neurosedyn; Softenon; Thalomid (Celgene).
C13H10N2O4; mol wt 258.23.
C 60.47%, H 3.90%, N 10.85%, O 24.78%.

Description and references

Selective inhibitor of tumor necrosis factor α (TNF-α). Formerly used as sedative, hypnotic. Prepn: GB 768821 (1957 to Chemie Grünenthal). Teratogenicity studies: I. D. Fratta et al., Toxicol. Appl. Pharmacol. 7, 268 (1965). Review of proposed mechanisms of embryopathy: T. D. Stephens, Teratology 38, 229-239 (1988). HPLC determn in plasma: A. Delon et al., J. Liq. Chromatogr. 18, 297 (1995). Stereospecific determn and pharmacokinetics of enantiomers: T. Eriksson et al., Chirality 7, 44 (1995). Clinical trial in HIV wasting syndrome: G. Reyes-Terán et al., AIDS 10, 1501 (1996); in aphthous ulcers related to HIV infection: J. M. Jacobson et al., N. Engl. J. Med. 336, 1487 (1997). Review of chemistry, pharmacokinetics and clinical safety: V. Günzler, Drug Saf. 7, 116-134 (1992); of effect on TNF-α and clinical use in leprosy and tuberculosis: J. D. Klausner et al., Clin. Immunol. Immunopathol. 81, 219-223 (1996); of pharmacology, history and potential clinical uses: D. Stirling et al., J. Am. Pharm. Assoc. NS37, 307-313 (1997); of use in multiple myeloma: S. V. Rajkumar, Expert Rev. Anticancer Ther.1, 20-28 (2001); of pharmacology and toxicology: C. Meierhofer, C. J. Wiedermann, Curr. Opin. Drug Discov. Devel. 6, 92-99 (2003); of clinical experience: S. J. Matthews, C. McCoy, Clin. Ther. 25, 342-395 (2003).

Chemical structure

Properties

Needles, mp 269-271°. uv max (neutral soln): 220, 300 nm. Soly in water: ≈2 × 10-4 mol/L; 45-60 mg/L. Sparingly sol in water, methanol, ethanol, acetone, ethyl acetate, butyl acetate, glacial acetic acid. Very sol in dioxane, DMF, pyridine. Practically insol in ether, chloroform, benzene.

Therapeutic Category

Immunomodulator.

Keywords

Sedative/Hypnotic; Piperidinediones; Immunomodulator