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Also known as: 163451-81-8, 108605-62-5, Aubagio, Flucyamide, A77 1726, Hmr1726
Molecular Formula
C12H9F3N2O2
Molecular Weight
270.21  g/mol
InChI Key
UTNUDOFZCWSZMS-YFHOEESVSA-N
FDA UNII
1C058IKG3B

Teriflunomide
Teriflunomide is the active metabolite of leflunomide, and it acts as an immunomodulatory agent by inhibiting pyrimidine synthesis. It is marketed under the name Aubagio and is indicated for the treatment of multiple sclerosis, specifically relapsing forms. The FDA label states an important warning about the risk of hepatoxicity and teratogenicity for patients using teriflunomide.
Teriflunomide is a Pyrimidine Synthesis Inhibitor. The mechanism of action of teriflunomide is as a Dihydroorotate Dehydrogenase Inhibitor.
1 2D Structure

Teriflunomide

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(Z)-2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]but-2-enamide
2.1.2 InChI
InChI=1S/C12H9F3N2O2/c1-7(18)10(6-16)11(19)17-9-4-2-8(3-5-9)12(13,14)15/h2-5,18H,1H3,(H,17,19)/b10-7-
2.1.3 InChI Key
UTNUDOFZCWSZMS-YFHOEESVSA-N
2.1.4 Canonical SMILES
CC(=C(C#N)C(=O)NC1=CC=C(C=C1)C(F)(F)F)O
2.1.5 Isomeric SMILES
C/C(=C(\C#N)/C(=O)NC1=CC=C(C=C1)C(F)(F)F)/O
2.2 Other Identifiers
2.2.1 UNII
1C058IKG3B
2.3 Synonyms
2.3.1 MeSH Synonyms

1. (2z)-2-cyano-3-hydroxy-n-(4-(trifluoromethyl)phenyl)-2-butenamide

2. (z)-2-cyano-3-hydroxy-n-(4-(trifluoromethyl)phenyl)-2-butenamide

3. 2-cyano-3-hydroxy-n-(4-(trifluoromethyl)phenyl)-2-butenamide

4. 2-hydroxyethylidene-cyanoacetic Acid-4-trifluoromethyl Anilide

5. A 1726

6. A 771726

7. A-771726

8. A77 1726

9. A771726

10. Aubagio

11. Hmr-1726

12. Hmr1726

13. Rs 61980

2.3.2 Depositor-Supplied Synonyms

1. 163451-81-8

2. 108605-62-5

3. Aubagio

4. Flucyamide

5. A77 1726

6. Hmr1726

7. Hmr-1726

8. (z)-2-cyano-3-hydroxy-n-(4-(trifluoromethyl)phenyl)but-2-enamide

9. Hmr 1726

10. A 771726

11. A-771726

12. Su 20

13. A771726

14. Teriflunomide(random Configuration)

15. (z)-2-cyano-3-hydroxy-n-[4-(trifluoromethyl)phenyl]but-2-enamide

16. A 77-1726

17. Leflunomide Related Compound B

18. (e/z)-teriflunomide

19. Chebi:68540

20. 2-cyano-3-hydroxy-n-(4-(trifluoromethyl)phenyl)-2-butenamide

21. (2z)-2-cyano-3-hydroxy-n-[4-(trifluoromethyl)phenyl]but-2-enamide

22. (z)-2-cyano-alpha,alpha,alpha-trifluoro-3-hydroxy-p-crotonotoluidide

23. 2-butenamide, 2-cyano-3-hydroxy-n-[4-(trifluoromethyl)phenyl]-, (2z)-

24. 1c058ikg3b

25. A77-1726

26. Teriflunomide (usan)

27. Teriflunomide [inn]

28. 2-butenamide, 2-cyano-3-hydroxy-n-(4-(trifluoromethyl)phenyl)-

29. Teriflunomide [usan]

30. 2-cyano-3-oh-n-(4-trifluoromethylphenyl)croton Amide

31. 2-butenamide, 2-cyano-3-hydroxy-n-[4-(trifluoromethyl)phenyl]-

32. (z)-2-cyano-3-hydroxy-n-(4-(trifluoromethyl)phenyl)but-2-enamide.

33. Mfcd00910058

34. Rs 61980

35. Teriflunomide [usan:inn]

36. Teriflunomida

37. Teriflunomidum

38. Unii-1c058ikg3b

39. 2-cyano-3-hydroxy-n-[4-(trifluoromethyl)phenyl]-2-butenamide

40. Malononitrilamide

41. N-(4-trifluoromethylphenyl)-2-cyano-2-hydroxycrotonamide

42. 2-hydroxyethylidene-cyanoacetic Acid-4-trifluoromethyl Anilide

43. 2-butenamide, 2-cyano-3-hydroxy-n-(4-(trifluoromethyl)phenyl)-, (2z)-

44. A 1726

45. A26

46. Aubagio (tn)

47. Su-0020

48. Leflunomide Impurity B

49. Rs-61980

50. Leflunomide Ep Impurity B

51. Teriflunomide [mi]

52. (2z)-2-[hydroxy-[4-(trifluoromethyl)anilino]methylidene]-3-oxobutanenitrile

53. Dimethyl Aprobarbital

54. Schembl22661

55. Teriflunomide [vandf]

56. Teriflunomide(a-771726)

57. Teriflunomide, A77 1726

58. Teriflunomide [who-dd]

59. Gtpl6844

60. Dtxsid80893457

61. Leflunomide Related Compound B Rs

62. A77 1726 (e/z) Mixture

63. Teriflunomide [orange Book]

64. Teriflunomide [ep Monograph]

65. Bdbm50018011

66. Nsc766118

67. S4169

68. Zinc13512456

69. Akos015994773

70. Ccg-267145

71. Db08880

72. Le-0275

73. Nsc-766118

74. Ncgc00263218-07

75. Ncgc00263218-13

76. Ac-26446

77. Hy-110159

78. Cs-0033021

79. Leflunomide Impurity B [ep Impurity]

80. Sw219377-1

81. T3287

82. Leflunomide-d4 Metabolite (teriflunomide-d4)

83. D10172

84. Leflunomide Related Compound B [usp-rs]

85. Ab01565775_02

86. A801897

87. A882574

88. J-010046

89. Q3077133

90. Leflunomide Related Compound B [usp Impurity]

91. N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxycrotonamide

92. N-[4-(trifluoromethyl)phenyl]-2-cyano-3-hydroxycrotonamide

93. 2-cyano-3-hydroxy-n-[4-(trifluoromethyl)phenyl]-2z-butenamide

94. (z)-2-cyano-3-hydroxy-n-[4-(trifluoromethyl)phenyl]-2-butenamide

95. 163451-81-8 (z Isomer) , 108605-62-5 (e/z Mixture)

96. 2-butenamide, 2-cyano-3-hydroxy-n-(4-(trifluoromethyl)phenyl)-, (z)-

97. A 77-1726;a771726;hmr1726;cas# 108605-62-5

98. (2z)-2-cyano-3-hydroxy-n-[4-(trifluoromethyl)phenyl]but-2-enamide (teriflunomide)

99. 2-cyano-3-hydroxy-n-(4-(trifluoromethyl)phenyl)but-2-enamide (e/z)-mixture

100. Leflunomide Related Compound B, United States Pharmacopeia (usp) Reference Standard

101. A 1726, A77-1726, A771726, Flucyamide, Hmr 1726, N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxycrotoamide, Su 20

102. Teriflunomide; Leflunomide Usp Rc B; Cyano Keto Leflunomide Impurity; N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxycrotonamide; 2-cyano-3-hydroxy-n-[4-(trifluoromethyl)phenyl]-2-beuteamide

2.4 Create Date
2011-12-26
3 Chemical and Physical Properties
Molecular Weight 270.21 g/mol
Molecular Formula C12H9F3N2O2
XLogP33.3
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count6
Rotatable Bond Count2
Exact Mass270.06161202 g/mol
Monoisotopic Mass270.06161202 g/mol
Topological Polar Surface Area73.1 Ų
Heavy Atom Count19
Formal Charge0
Complexity426
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count1
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 2  
Drug NameAubagio
PubMed HealthTeriflunomide (By mouth)
Drug ClassesCentral Nervous System Agent, Immune Modulator
Active IngredientTeriflunomide
Dosage FormTablet
RouteOral
Strength14mg; 7mg
Market StatusPrescription
CompanySanofi Aventis Us

2 of 2  
Drug NameAubagio
PubMed HealthTeriflunomide (By mouth)
Drug ClassesCentral Nervous System Agent, Immune Modulator
Active IngredientTeriflunomide
Dosage FormTablet
RouteOral
Strength14mg; 7mg
Market StatusPrescription
CompanySanofi Aventis Us

4.2 Drug Indication

Used in the treatment of relapsing forms of multiple sclerosis (MS).


FDA Label


AUBAGIO is indicated for the treatment of adult patients and paediatric patients aged 10 years and older with relapsing remitting multiple sclerosis (MS) (please refer to section 5. 1 for important information on the population for which efficacy has been established).


5 Pharmacology and Biochemistry
5.1 Pharmacology

Teriflunomide is an immunomodulatory agent that decreases the amount of activated CNS lymphocytes, which results in anti-inflammatory and antiproliferative effects.


5.2 MeSH Pharmacological Classification

Anti-Inflammatory Agents, Non-Steroidal

Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)


Immunosuppressive Agents

Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. (See all compounds classified as Immunosuppressive Agents.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
TERIFLUNOMIDE
5.3.2 FDA UNII
1C058IKG3B
5.3.3 Pharmacological Classes
Pyrimidine Synthesis Inhibitor [EPC]; Dihydroorotate Dehydrogenase Inhibitors [MoA]
5.4 ATC Code

L04AA31


L04AA31

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355


L - Antineoplastic and immunomodulating agents

L04 - Immunosuppressants

L04A - Immunosuppressants

L04AA - Selective immunosuppressants

L04AA31 - Teriflunomide


5.5 Absorption, Distribution and Excretion

Absorption

After oral administration of teriflunomide, maximum plasma concentrations are reached, on average, in 1-4 hours.


Route of Elimination

Teriflunomide is eliminated unchanged and mainly through bile. Specifically 37.5% is eliminated in the feces and 22.6% in urine.


Volume of Distribution

After a single intravenous dose, the volume of distribution is 11 L.


Clearance

After a single IV dose, teriflunomide has a total body clearance of 30.5 mL/h.


5.6 Metabolism/Metabolites

Teriflunomide mainly undergoes hydrolyis to minor metabolites. Other minor metabolic pathways include oxidation, N-acetylation and sulfate conjugation. Teriflunomide is not metabolized by CYP450 or flavin monoamine oxidase.


5.7 Biological Half-Life

The median half-life is 18 to 19 days.


5.8 Mechanism of Action

The exact mechanism by which teriflunomide acts in MS is not known. What is known is that teriflunomide prevents pyrimidine synthesis by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase, and this may be involved in its immunomodulatory effect in MS.


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23-Feb-2021
15-Jul-2024
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DOSAGE - TABLET;ORAL - 14MG

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DOSAGE - TABLET;ORAL - 7MG

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