5432. Leflunomide

Nomenclature

CAS number: 75706-12-6
5-Methyl-N-[4-(trifluoromethyl)phenyl]-4-isoxazolecarboxamide; α,α,α-trifluoro-5-methyl-4-isoxazolecarboxy-p-toluidide; 5-methylisoxazole-4-carboxylic acid trifluoromethylanilide; HWA-486; Arava (Sanofi-Aventis).
C12H9F3N2O2; mol wt 270.21.
C 53.34%, H 3.36%, F 21.09%, N 10.37%, O 11.84%.

Description and references

Disease modifying antirheumatic drug (DMARD) with immunosuppressant activity. Converted in vivo to its active open ring metabolite, teriflunomide, q.v. Inhibits de novo pyrimidine biosynthesis in immune cells. Prepn: F. J. Kaemmerer, R. Schleyerbach, DE 2854439; eidem, US 4284786 (1980, 1981 both to Hoechst); and pharmacology: P. Fossa et al., Farmaco 46, 789 (1991). HPLC determn of active metabolite in plasma: V. C. Dias et al., Ther. Drug Monit. 17, 84 (1995). Review of mechanisms of action: R. I. Fox, J. Rheumatol. 25, Suppl. 53, 20-26 (1998); of clinical pharmacology: B. Rozman, ibid. 27-32. Clinical trial in rheumatoid arthritis: V. Strand et al., Arch. Intern. Med. 159, 2542 (1999). Reviews: C. Miceli-Richard, M. Dougados, Expert Opin. Pharmacother. 4, 987-997 (2003); J. P. Kaltwasser, F. Behrens, ibid. 6, 787-801 (2005).

Chemical structure

Properties

Crystals from toluene, mp 166.5°. pKa 10.8. Soly in water (25°): 25 - 27 mg/l. Sol in methanol, ethanol, acetone.

Therapeutic Category

Antirheumatic.

Keywords

Antiarthritic/Antirheumatic; Immunomodulator