Teriflunomide

Drugbox
IUPAC_name = (Z)-2-Cyano-3-hydroxy-N- [4-(trifluoromethyl)phenyl] -2-butenamide

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CAS_number = 163451-81-8
CAS_supplemental =
ATC_prefix =
ATC_suffix =
ATC_supplemental =
PubChem = 5479847
DrugBank =
chemical_formula =
C=12 | H=9 | F=3 | N=2 | O=2
molecular_weight = 270.207 g/mol
smiles = N#CC(=C(/C)O)C(=O)Nc1ccc(C(F)(F)F)cc1
bioavailability =
protein_bound = >99.3%
metabolism =
elimination_half-life = 2 weeks
excretion = Biliar, renal
pregnancy_AU =
pregnancy_US =
pregnancy_category= X (contraindicated)
legal_AU =
legal_CA =
legal_UK =
legal_US =
legal_status =
routes_of_administration = Oral

Teriflunomide (previously A77 1726) is the active metabolite of leflunomide.cite journal |author=Magne D, Mézin F, Palmer G, Guerne PA |title=The active metabolite of leflunomide, A77 1726, increases proliferation of human synovial fibroblasts in presence of IL-1beta and TNF-alpha |journal=Inflamm. Res. |volume=55 |issue=11 |pages=469–75 |year=2006 |pmid=17122964 |doi=10.1007/s00011-006-5196-x] Like leflunomide, it is used for rheumatoid arthritis. [cite journal
author = Boyd, B, Castaner, J
title = Teriflunomide
journal = Drugs of the Future
year = 2005
volume = 30
issue = 11
pages = 1102 ] As of|September 2008, teriflunomide is investigated in the Phase III clinical trial TEMSO as a medication for multiple sclerosis (MS). [ [http://clinicaltrials.gov/show/NCT00134563 ClinicalTrials.gov] ]

Mechanisms of action

Teriflunomide is an immunomodulatory drug inhibiting pyrimidine de novo synthesis by blocking the enzyme dihydroorotate dehydrogenase. It is uncertain whether this explains its effect on MS lesions. [cite journal
author = H. Spreitzer
date = March 13, 2006
title = Neue Wirkstoffe - Teriflunomid
journal = Österreichische Apothekerzeitung
issue = 6/2006
language = German ]

It has been found that teriflunomid blocks the transcription factor NF-κB. It also inhibits tyrosine kinase enzymes, but only in high doses not clinically used. [cite journal|last=Breedveld|first=FC|coauthors=Dayer, J-M|date=November 2000|title=Leflunomide: mode of action in the treatment of rheumatoid arthritis|journal=Ann Rheum Dis|volume=59|pages=841 - 849]

Activation of leflunomide to teriflunomide

The structure which results from ring opening can interconvert between the "E" and "Z" enolic forms (and the corresponding keto-amide), with the "Z" enol being the most stable and therefore most predominant form.

ee also

See Leflunomide for information on pharmacokinetics, side-effects, contraindications and other data.

References