A77 1726 CAS NO.163451-81-8

Product Name:    A77 1726
Synonyms:    A77 1726 (Teriflunomide);A 1726;Flucyamide;HMR 1726;(Z)-2-Cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide;LeflunoMide EP IMpurity B;Leflunomide Impurity 2(Leflunomide EP Impurity B);A-771726;A 771726;A771726
CAS:    163451-81-8
MF:    C12H9F3N2O2
MW:    270.21
EINECS:    642-273-4
Product Categories:    Metabolites & Impurities;Tyrosine Kinase Inhibitors
Mol File:    163451-81-8.mol
 

Melting point     229-232°C
Boiling point     410.8±45.0 °C(Predicted)
density     1.424±0.06 g/cm3(Predicted)
storage temp.     -20°C
solubility     DMSO: soluble5mg/mL, clear (warmed)
form     powder
pka    5.20±0.50(Predicted)
color     white to beige
λmax    203nm(MeOH)(lit.)
Merck     14,9165
InChIKey    UTNUDOFZCWSZMS-YFHOEESVSA-N
CAS DataBase Reference    163451-81-8
Safety Information
Hazard Codes     Xn
Risk Statements     22
WGK Germany     3
MSDS Information
A77 1726 Usage And Synthesis
Description    In September 2012, the US FDA approved teriflunomide (also referred to as HMR-1726) as a therapy for patients with relapsing forms of multiple sclerosis (MS). Teriflunomide is the second approved oral treatment option for MS, after Gilenya which was approved in 2010. Teriflunomide, which is the active metabolite of leflunomide (a marketed drug for the treatment of rheumatoid and psoriatic arthritis), is a non competitive and selective inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme in the de novo synthesis of pyrimidines. Although the net effect of inhibition of DHODH by teriflunomide and its therapeutic effect in MS are not clear, it is hypothesized that by inhibiting de novo pyrimidine synthesis, the effector functions of activated lymphocytes are suppressed, thus dampening the effect of an overactive immune system.
Description    A-771726 is an active metabolite of the prodrug leflunomide (Item No. 14860) that inhibits dihydroorotate dehydrogenase (DHODH; IC50 = 0.23 μM). A-771726 inhibits the production of prostaglandin E2 (PGE2; Item No. 14010) in TNF-α- or IL-1α-stimulated isolated human synoviocytes (IC50s = 7 and 3 μM, respectively). It inhibits the proliferation of isolated human peripheral blood mononuclear cells (PBMCs) when used at concentrations of 25 and 100 μM. A-771726 (3 and 10 mg/kg) delays disease onset and decreases neurological deficits in a rat model of experimental autoimmune encephalomyelitis (EAE) induced by complete Freund’s adjuvant (CFA) and M. tuberculosis. Formulations containing teriflunomide have been used in the treatment of multiple sclerosis.