Leflunomide (CED0002601)

Record Information
Version1.0
Creation Date2016-05-22 03:42:43 UTC
Update Date2026-08-18 22:06:30 UTC
Accession NumberCHEM016754
Identification
Common NameLeflunomide
ClassSmall Molecule
Description
Leflunomide is an organic compound with the formula C12H9F3N2O2 and an average molecular weight of 270.21 g/mol. Leflunomide belongs to the anilides, a subclass of benzene and substituted derivatives within the organic compounds. It is recorded as being found in or released from 14 sources, including healthcare, pharmaceuticals & veterinary products (immunosuppressants), food, food processing & cookware (food preservation, processing meats), household cleaning & consumer products (cigar cigarettes, non electric simulated smoking devices, other smoking requisites, tobacco smoke filters), and electrical & electronic equipment (electric hearing aids, electric switches, electrically stimulated smoking devices, electrodes, hybrid capacitors, and 2 more). Exposure routes for this compound are recorded as topical and oral. At the molecular level, leflunomide acts on four recorded protein targets as an agonist, antagonist, or inhibitor, specifically targeting the aryl hydrocarbon receptor (AHR), protein-tyrosine kinase 2-beta (PTK2B), and dihydroorotate dehydrogenase (quinone), mitochondrial (DHODH). In terms of health effects, the compound is used as a treatment for rheumatoid arthritis (PMC8933701) and psoriasis (PMC4893110).
Contaminant Type
  • Human Neurotoxin
Chemical Structure
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
5-Methyl-N-(4-(trifluoromethyl)phenyl)-4-isoxazolecarboxamideChEBI
5-Methylisoxazole-4-carboxylic acid (4-trifluoromethyl)anilideChEBI
alpha,alpha,alpha-Trifluoro-5-methyl-4-isoxazolecarboxy-p-toluidideChEBI
AravaChEBI
LeflunomidaChEBI
LeflunomidumChEBI
5-Methylisoxazole-4-carboxylate (4-trifluoromethyl)anilideGenerator
a,a,a-Trifluoro-5-methyl-4-isoxazolecarboxy-p-toluidideGenerator
Α,α,α-trifluoro-5-methyl-4-isoxazolecarboxy-p-toluidideGenerator
Aventis behring brand OF leflunomideHMDB
Aventis brand OF leflunomideHMDB
HWA 486HMDB
HWA-486HMDB
Aventis pharma brand OF leflunomideHMDB
Hoechst brand OF leflunomideHMDB
N-(4-Trifluoromethyphenyl)-5-methylisoxazole-4-carboxamideHMDB
Chemical FormulaC12H9F3N2O2
Average Molecular Mass270.207 g/mol
Monoisotopic Mass270.062 g/mol
CAS Registry Number75706-12-6
IUPAC Name5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide
Traditional Nameleflunomide
SMILESCC1=C(C=NO1)C(=O)NC1=CC=C(C=C1)C(F)(F)F
InChI IdentifierInChI=1S/C12H9F3N2O2/c1-7-10(6-16-19-7)11(18)17-9-4-2-8(3-5-9)12(13,14)15/h2-6H,1H3,(H,17,18)
InChI KeyVHOGYURTWQBHIL-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as aromatic anilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with an aromatic group. They have the general structure RNC(=O)R', where R= benzene, and R = aryl group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassAnilides
Direct ParentAromatic anilides
Alternative Parents
Substituents
  • Aromatic anilide
  • Trifluoromethylbenzene
  • Azole
  • Isoxazole
  • Heteroaromatic compound
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Carboxylic acid derivative
  • Organoheterocyclic compound
  • Azacycle
  • Oxacycle
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Organopnictogen compound
  • Alkyl fluoride
  • Organic oxygen compound
  • Alkyl halide
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginNot Available
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Organoleptic EffectsNot Available
Physical Properties
StateNot Available
AppearanceNot Available
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.084 g/LALOGPS
logP2.52ALOGPS
logP2.51ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)10.41ChemAxon
pKa (Strongest Basic)-0.45ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area55.13 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity64.16 m³·mol⁻¹ChemAxon
Polarizability23.11 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrumsplash10-03di-7970000000-03045269425a638f328cNot AvailableView Spectrum
Predicted GC-MSPredicted GC-MS SpectrumNot AvailableNot AvailableView Spectrum
Predicted GC-MSPredicted GC-MS SpectrumNot AvailableNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-00di-0390000000-1ac4065d1ef245442a16Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-05gi-3920000000-db0dc9413f5ca5cb69e3Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-00di-0390000000-1ac4065d1ef245442a16Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-03di-2920000000-819d0674f452a60be1a4Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-00lr-9200000000-414a713461b4237c6e71Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-001i-9200000000-e21878adb74f0a5190bcNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-00lr-9050000000-6c169fcd04bf0a4c16a8Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-001i-9110000000-459c33159bb27094ea91Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-001i-9200000000-a48fe3379802d9cfce95Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-001i-9200000000-19d3236cea84dc0f5ff1Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-001i-9200000000-0ef7ffe353ea10020f8dNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-00di-0390000000-e07a793be0a4de994083Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-03di-1930000000-dbdbb3e67b067703099dNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-03di-7900000000-24b45cc5af1bf1c20902Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-014i-3090000000-039b17df86bfcf213d45Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-001i-9010000000-95fb3f6c8f86b32a3a33Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-01q9-9100000000-0bee5f2dec9154ee9333Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-00di-1190000000-320ce8ab21656bf61a98Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-00di-2490000000-e7bd4a27fe1066098f17Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-01ox-9320000000-01ed6f4bd00aeceec987Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-0159-5090000000-2d9438c678553c6a4277Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-03di-2920000000-70daf72ac22ca58c8b59Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-03di-0900000000-f53ae2f06f61c346c9e3Not AvailableView Spectrum
Toxicity Profile
Mechanism of ToxicityNot Available
Carcinogenicity (IARC Classification)Not Available
Minimum Risk LevelNot Available
SymptomsNot Available
TreatmentNot Available
Toxicity Values
Toxicity ValueUnitValue RangeOrganismDose DescriptorRoute of ExposurePredicted or ExperimentalReference
242.0Log mg/kg[140:430]RatLD50oralpredictedNot Available
Health Effects
Health EffectRelationshipDirectionReference
rheumatoid arthritisis_treatment_forNot AvailablePMC8933701
psoriasisis_treatment_forNot AvailablePMC4893110
Exposure Sources
Source IDSourceSectorReference
10InsecticidesAgriculture & land managementNot Available
362ImmunosuppressantsHealthcare, pharmaceuticals & veterinary productsNot Available
516Electric Hearing AidsElectrical & Electronic EquipmentNot Available
517Electric SwitchesElectrical & Electronic EquipmentNot Available
518Electrically Stimulated Smoking DevicesElectrical & Electronic EquipmentNot Available
519ElectrodesElectrical & Electronic EquipmentNot Available
524Hybrid CapacitorsElectrical & Electronic EquipmentNot Available
530Radio Transmission SystemsElectrical & Electronic EquipmentNot Available
537Television SystemsElectrical & Electronic EquipmentNot Available
545Food PreservationFood, food processing & cookwareNot Available
552Processing MeatsFood, food processing & cookwareNot Available
556Cigar CigarettesHousehold cleaning & consumer productsNot Available
559Non Electric Simulated Smoking DevicesHousehold cleaning & consumer productsNot Available
560Other Smoking RequisitesHousehold cleaning & consumer productsNot Available
569Tobacco Smoke FiltersHousehold cleaning & consumer productsNot Available
580Manufacture Preparation Of Tobacco ProductsIndustrial manufacturing & chemical processingNot Available
583Anchoring EquipmentMarine, shipping & aquacultureNot Available
590Lifeboat EquipmentMarine, shipping & aquacultureNot Available
592Marine Propulsion Or SteeringMarine, shipping & aquacultureNot Available
596AcaricidesAgriculture & land managementNot Available
600Herbicides And AlgicidesAgriculture & land managementNot Available
606Plant Growth RegulatorsAgriculture & land managementNot Available
611Anti Perspirants Or Body DeoderantsPersonal care & cosmeticsNot Available
613DepilatoriesPersonal care & cosmeticsNot Available
615Eye Makeup ProductsPersonal care & cosmeticsNot Available
632ApparelTextiles, leather & furnishingsNot Available
655Slide FastenersTextiles, leather & furnishingsNot Available
Pathways
1 pathway
Leflunomide Drug Metabolism Action Pathway
Leflunomide Drug Metabolism Action Pathway
Targets
StructureProteinUniProt IDOrganismRelationshipDetails
Cytochrome P450 1A2 structureClick to view 3D structureCytochrome P450 1A2P05177HumansPredicted (SEA)31.3732
Dihydroorotate dehydrogenase (quinone), mitochondrial structureClick to view 3D structureDihydroorotate dehydrogenase (quinone), mitochondrialQ02127HumansPredicted (SEA)0.544945
Click to view 3D structureDihydroorotate dehydrogenase (quinone), mitochondrialQ63707Rattus norvegicusPredicted (SEA)0.467095
Click to view 3D structureLuciferin 4-monooxygenaseP08659Photinus pyralisPredicted (SEA)2.25763
Vascular endothelial growth factor receptor 2 structureClick to view 3D structureVascular endothelial growth factor receptor 2P35968HumansPredicted (SEA)273.562
Macrophage colony-stimulating factor 1 receptor structureClick to view 3D structureMacrophage colony-stimulating factor 1 receptorP07333HumansPredicted (SEA)151.417
Tyrosine-protein kinase Lck structureClick to view 3D structureTyrosine-protein kinase LckP06239HumansPredicted (SEA)221.403
Click to view 3D structureDihydroorotate dehydrogenase (quinone), mitochondrialO35435Mus musculusPredicted (SEA)0.622794
Mitogen-activated protein kinase 14 structureClick to view 3D structureMitogen-activated protein kinase 14Q16539HumansPredicted (SEA)125.726
Mast/stem cell growth factor receptor Kit structureClick to view 3D structureMast/stem cell growth factor receptor KitP10721HumansPredicted (SEA)197.27
Sodium-dependent dopamine transporter structureClick to view 3D structureSodium-dependent dopamine transporterQ01959HumansPredicted (SEA)55.0394
Sodium-dependent noradrenaline transporter structureClick to view 3D structureSodium-dependent noradrenaline transporterP23975HumansPredicted (SEA)54.1831
Serine/threonine-protein kinase B-raf structureClick to view 3D structureSerine/threonine-protein kinase B-rafP15056HumansPredicted (SEA)94.1976
Proto-oncogene tyrosine-protein kinase Src structureClick to view 3D structureProto-oncogene tyrosine-protein kinase SrcP12931HumansPredicted (SEA)345.106
Click to view 3D structureCyclic AMP-dependent transcription factor ATF-1P18846HumansPredicted (SEA)1.32344
Apolipoprotein B-100 structureClick to view 3D structureApolipoprotein B-100P04114HumansPredicted (SEA)1.08989
Tyrosine-protein kinase BTK structureClick to view 3D structureTyrosine-protein kinase BTKQ06187HumansPredicted (SEA)369.161
Tyrosine-protein kinase Lyn structureClick to view 3D structureTyrosine-protein kinase LynP07948HumansPredicted (SEA)288.198
Tyrosine-protein kinase ABL1 structureClick to view 3D structureTyrosine-protein kinase ABL1P00519HumansPredicted (SEA)354.058
Click to view 3D structureTransmembrane protease serine 4Q9NRS4HumansPredicted (SEA)2.56902
RAF proto-oncogene serine/threonine-protein kinase structureClick to view 3D structureRAF proto-oncogene serine/threonine-protein kinaseP04049HumansPredicted (SEA)130.242
Exportin-1 structureClick to view 3D structureExportin-1O14980HumansPredicted (SEA)2.10193
P2X purinoceptor 1 structureClick to view 3D structureP2X purinoceptor 1P51575HumansPredicted (SEA)30.9061
Cytochrome P450 2C9 structureClick to view 3D structureCytochrome P450 2C9P11712HumansPredicted (SEA)519.41
Angiopoietin-1 receptor structureClick to view 3D structureAngiopoietin-1 receptorQ02763HumansPredicted (SEA)195.791
Concentrations
Not Available
External Links
DrugBank IDDB01097
HMDB IDHMDB0015229
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkLeflunomide
Chemspider ID3762
ChEBI ID6402
PubChem Compound ID3899
Kegg Compound IDC07905
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
1. Fox RI: Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl. 1998 Jul;53:20-6.
2. Herrmann ML, Schleyerbach R, Kirschbaum BJ: Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Immunopharmacology. 2000 May;47(2-3):273-89.
3. Schattenkirchner M: The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review. Immunopharmacology. 2000 May;47(2-3):291-8.
4. Goldenberg MM: Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis. Clin Ther. 1999 Nov;21(11):1837-52; discussion 1821.
5. Breedveld FC, Dayer JM: Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis. 2000 Nov;59(11):841-9.
6. Sanders S, Harisdangkul V: Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. Am J Med Sci. 2002 Apr;323(4):190-3.
7. Li EK, Tam LS, Tomlinson B: Leflunomide in the treatment of rheumatoid arthritis. Clin Ther. 2004 Apr;26(4):447-59.
8. https://www.ncbi.nlm.nih.gov/pubmed/?term=10515382
9. https://www.ncbi.nlm.nih.gov/pubmed/?term=10702725
10. https://www.ncbi.nlm.nih.gov/pubmed/?term=10890256
11. https://www.ncbi.nlm.nih.gov/pubmed/?term=11043056
12. https://www.ncbi.nlm.nih.gov/pubmed/?term=11053058
13. https://www.ncbi.nlm.nih.gov/pubmed/?term=11067959
14. https://www.ncbi.nlm.nih.gov/pubmed/?term=11271257
15. https://www.ncbi.nlm.nih.gov/pubmed/?term=11333342
16. https://www.ncbi.nlm.nih.gov/pubmed/?term=11340750
17. https://www.ncbi.nlm.nih.gov/pubmed/?term=11391470
18. https://www.ncbi.nlm.nih.gov/pubmed/?term=11475244
19. https://www.ncbi.nlm.nih.gov/pubmed/?term=11522581
20. https://www.ncbi.nlm.nih.gov/pubmed/?term=11707749
21. https://www.ncbi.nlm.nih.gov/pubmed/?term=11718154
22. https://www.ncbi.nlm.nih.gov/pubmed/?term=11876141
23. https://www.ncbi.nlm.nih.gov/pubmed/?term=11884931
24. https://www.ncbi.nlm.nih.gov/pubmed/?term=11994686
25. https://www.ncbi.nlm.nih.gov/pubmed/?term=12017890
26. https://www.ncbi.nlm.nih.gov/pubmed/?term=12074690
27. https://www.ncbi.nlm.nih.gov/pubmed/?term=12833393
28. https://www.ncbi.nlm.nih.gov/pubmed/?term=14622739
29. https://www.ncbi.nlm.nih.gov/pubmed/?term=15030575
30. https://www.ncbi.nlm.nih.gov/pubmed/?term=15127968
31. https://www.ncbi.nlm.nih.gov/pubmed/?term=15127974
32. https://www.ncbi.nlm.nih.gov/pubmed/?term=15188371
33. https://www.ncbi.nlm.nih.gov/pubmed/?term=15214907
34. https://www.ncbi.nlm.nih.gov/pubmed/?term=15385935
35. https://www.ncbi.nlm.nih.gov/pubmed/?term=15489872
36. https://www.ncbi.nlm.nih.gov/pubmed/?term=15537652
37. https://www.ncbi.nlm.nih.gov/pubmed/?term=15652966
38. https://www.ncbi.nlm.nih.gov/pubmed/?term=15665760
39. https://www.ncbi.nlm.nih.gov/pubmed/?term=15789891
40. https://www.ncbi.nlm.nih.gov/pubmed/?term=15899055
41. https://www.ncbi.nlm.nih.gov/pubmed/?term=15934905
42. https://www.ncbi.nlm.nih.gov/pubmed/?term=16106593
43. https://www.ncbi.nlm.nih.gov/pubmed/?term=16142756
44. https://www.ncbi.nlm.nih.gov/pubmed/?term=16202258
45. https://www.ncbi.nlm.nih.gov/pubmed/?term=16284916
46. https://www.ncbi.nlm.nih.gov/pubmed/?term=16638062
47. https://www.ncbi.nlm.nih.gov/pubmed/?term=16638420
48. https://www.ncbi.nlm.nih.gov/pubmed/?term=16645972
49. https://www.ncbi.nlm.nih.gov/pubmed/?term=16688677
50. https://www.ncbi.nlm.nih.gov/pubmed/?term=16769661
51. https://www.ncbi.nlm.nih.gov/pubmed/?term=16778342
52. https://www.ncbi.nlm.nih.gov/pubmed/?term=17366662
53. https://www.ncbi.nlm.nih.gov/pubmed/?term=17604599
54. https://www.ncbi.nlm.nih.gov/pubmed/?term=17646975
55. https://www.ncbi.nlm.nih.gov/pubmed/?term=17854740
56. https://www.ncbi.nlm.nih.gov/pubmed/?term=18034546
57. https://www.ncbi.nlm.nih.gov/pubmed/?term=18173611
58. https://www.ncbi.nlm.nih.gov/pubmed/?term=18413415
59. https://www.ncbi.nlm.nih.gov/pubmed/?term=18496682
60. https://www.ncbi.nlm.nih.gov/pubmed/?term=18663553
61. https://www.ncbi.nlm.nih.gov/pubmed/?term=18688040
62. https://www.ncbi.nlm.nih.gov/pubmed/?term=19169882
63. https://www.ncbi.nlm.nih.gov/pubmed/?term=19190124
64. https://www.ncbi.nlm.nih.gov/pubmed/?term=19344337
65. https://www.ncbi.nlm.nih.gov/pubmed/?term=19581389
66. https://www.ncbi.nlm.nih.gov/pubmed/?term=19715969
67. https://www.ncbi.nlm.nih.gov/pubmed/?term=19751817
68. https://www.ncbi.nlm.nih.gov/pubmed/?term=19770782
69. https://www.ncbi.nlm.nih.gov/pubmed/?term=7496341
70. https://www.ncbi.nlm.nih.gov/pubmed/?term=7676489
71. https://www.ncbi.nlm.nih.gov/pubmed/?term=8610393
72. https://www.ncbi.nlm.nih.gov/pubmed/?term=9075844
73. https://www.ncbi.nlm.nih.gov/pubmed/?term=9123314
74. https://www.ncbi.nlm.nih.gov/pubmed/?term=9625011
75. https://www.ncbi.nlm.nih.gov/pubmed/?term=9777697