Identification

Name
Carbimazole
Accession Number
DB00389  (APRD00503)
Type
Small Molecule
Groups
Approved, Investigational
Description

An imidazole antithyroid agent. Carbimazole is metabolized to methimazole, which is responsible for the antithyroid activity.

Structure
Thumb
Synonyms
  • 1H-Imidazole-1-carboxylic acid, 2,3-dihydro-3-methyl-2-thioxo-, ethyl ester Ethyl 3-methyl-2-thioimidazoline-1-carboxylate
  • Athyromazole
  • Carbethoxymethimazole
  • Carbimazol
  • Carbimazolo
  • Carbimazolum
  • Carbinazole
  • Ethyl 3-methyl-2-thioimidazoline-1-carboxylate
External IDs
CG 1
International/Other Brands
Camen (Dalim) / Carbimazol (Sanofi-Aventis) / Carbinom (XL Lab) / Carbizol (Square) / Neomercazole (Abbott) / Neomerdin (MedChoice) / Newmazole (Genuine) / Thyrocab (Abbott) / Thyrostat (Ni-The) / Tyrazol (Orion) / Upha Carbimazole (CCM)
Categories
UNII
8KQ660G60G
CAS number
22232-54-8
Weight
Average: 186.232
Monoisotopic: 186.046298264
Chemical Formula
C7H10N2O2S
InChI Key
CFOYWRHIYXMDOT-UHFFFAOYSA-N
InChI
InChI=1S/C7H10N2O2S/c1-3-11-7(10)9-5-4-8(2)6(9)12/h4-5H,3H2,1-2H3
IUPAC Name
ethyl 3-methyl-2-sulfanylidene-2,3-dihydro-1H-imidazole-1-carboxylate
SMILES
CCOC(=O)N1C=CN(C)C1=S

Pharmacology

Indication

For the treatment of hyperthyroidism and thyrotoxicosis. It is also used to prepare patients for thyroidectomy.

Structured Indications
Not Available
Pharmacodynamics

Carbimazole is a carbethoxy derivative of methimazole. Its antithyroid action is due to its conversion to methimazole after absorption. It is used to treat hyperthyroidism and thyrotoxicosis.

Mechanism of action

Carbimazole is an aitithyroid agent that decreases the uptake and concentration of inorganic iodine by thyroid, it also reduces the formation of di-iodotyrosine and thyroxine. Once converted to its active form of methimazole, it prevents the thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4.

TargetActionsOrganism
AThyroid peroxidase
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

85%

Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolCarbimazole may decrease the anticoagulant activities of Acenocoumarol.Approved
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be increased when it is combined with Carbimazole.Approved
AcetyldigoxinThe serum concentration of Acetyldigoxin can be increased when it is combined with Carbimazole.Experimental
Ambroxol acefyllinateThe serum concentration of Ambroxol acefyllinate can be increased when it is combined with Carbimazole.Experimental, Investigational
AminophyllineThe serum concentration of Aminophylline can be increased when it is combined with Carbimazole.Approved
ClorindioneCarbimazole may decrease the anticoagulant activities of Clorindione.Experimental
CymarinThe serum concentration of Cymarin can be increased when it is combined with Carbimazole.Experimental
DeslanosideThe serum concentration of Deslanoside can be increased when it is combined with Carbimazole.Approved
DicoumarolCarbimazole may decrease the anticoagulant activities of Dicoumarol.Approved
DigitoxinThe serum concentration of Digitoxin can be increased when it is combined with Carbimazole.Approved, Investigational
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Carbimazole.Approved
DiphenadioneCarbimazole may decrease the anticoagulant activities of Diphenadione.Experimental
DyphyllineThe serum concentration of Dyphylline can be increased when it is combined with Carbimazole.Approved
Ethyl biscoumacetateCarbimazole may decrease the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneCarbimazole may decrease the anticoagulant activities of Fluindione.Investigational
GitoformateThe serum concentration of Gitoformate can be increased when it is combined with Carbimazole.Experimental
Iodide I-131The therapeutic efficacy of Iodide I-131 can be decreased when used in combination with Carbimazole.Approved
Lanatoside CThe serum concentration of Lanatoside C can be increased when it is combined with Carbimazole.Experimental
MetildigoxinThe serum concentration of Metildigoxin can be increased when it is combined with Carbimazole.Experimental
OleandrinThe serum concentration of Oleandrin can be increased when it is combined with Carbimazole.Experimental, Investigational
OuabainThe serum concentration of Ouabain can be increased when it is combined with Carbimazole.Approved
PeruvosideThe serum concentration of Peruvoside can be increased when it is combined with Carbimazole.Experimental
PhenindioneCarbimazole may decrease the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonCarbimazole may decrease the anticoagulant activities of Phenprocoumon.Approved, Investigational
PrednisoloneThe serum concentration of Prednisolone can be decreased when it is combined with Carbimazole.Approved, Vet Approved
ProscillaridinThe serum concentration of Proscillaridin can be increased when it is combined with Carbimazole.Experimental
TheophyllineThe serum concentration of Theophylline can be increased when it is combined with Carbimazole.Approved
TioclomarolCarbimazole may decrease the anticoagulant activities of Tioclomarol.Experimental
TizanidineThe serum concentration of Tizanidine can be increased when it is combined with Carbimazole.Approved
WarfarinCarbimazole may decrease the anticoagulant activities of Warfarin.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB14533
KEGG Drug
D07616
KEGG Compound
C07615
PubChem Compound
31072
PubChem Substance
46506359
ChemSpider
28829
BindingDB
50275889
ChEBI
617099
ChEMBL
CHEMBL508102
Therapeutic Targets Database
DAP000762
PharmGKB
PA164742970
Wikipedia
Carbimazole
ATC Codes
H03BB01 — Carbimazole
MSDS
Download (57.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentPaediatric Thyrotoxicosis1
3RecruitingTreatmentGraves Diseases / Hyperthyroidism1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)123.5 °CPhysProp
logP0.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility3.14 mg/mLALOGPS
logP0.78ALOGPS
logP1.35ChemAxon
logS-1.8ALOGPS
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area32.78 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity49.17 m3·mol-1ChemAxon
Polarizability18.71 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9157
Blood Brain Barrier+0.9725
Caco-2 permeable+0.5
P-glycoprotein substrateNon-substrate0.8746
P-glycoprotein inhibitor INon-inhibitor0.7055
P-glycoprotein inhibitor IINon-inhibitor0.8618
Renal organic cation transporterNon-inhibitor0.8473
CYP450 2C9 substrateNon-substrate0.7914
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7238
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9383
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.925
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7529
Ames testNon AMES toxic0.7087
CarcinogenicityNon-carcinogens0.853
BiodegradationNot ready biodegradable0.9614
Rat acute toxicity2.7924 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9875
hERG inhibition (predictor II)Non-inhibitor0.813
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0900000000-c5aaa0a285a7152c688a

Taxonomy

Description
This compound belongs to the class of organic compounds known as carbonylimidazoles. These are substituted imidazoles in which the imidazole ring bears a carbonyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Imidazoles
Direct Parent
Carbonylimidazoles
Alternative Parents
N-substituted imidazoles / Imidazolethiones / Heteroaromatic compounds / Thioureas / Organic carbonic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organic oxides
show 1 more
Substituents
Imidazole-1-carbonyl group / Imidazole-2-thione / N-substituted imidazole / Heteroaromatic compound / Carbonic acid derivative / Thiourea / Azacycle / Organic nitrogen compound / Organosulfur compound / Organooxygen compound
show 6 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
carbamate ester, imidazoles, thioureas (CHEBI:617099)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Peroxidase activity
Specific Function
Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4).
Gene Name
TPO
Uniprot ID
P07202
Uniprot Name
Thyroid peroxidase
Molecular Weight
102961.63 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Guilhem I, Massart C, Poirier JY, Maugendre D: Differential evolution of thyroid peroxidase and thyrotropin receptor antibodies in Graves' disease: thyroid peroxidase antibody activity reverts to pretreatment level after carbimazole withdrawal. Thyroid. 2006 Oct;16(10):1041-5. [PubMed:17042691]
  3. Magnusson RP, Taurog A, Dorris ML: Mechanism of iodide-dependent catalatic activity of thyroid peroxidase and lactoperoxidase. J Biol Chem. 1984 Jan 10;259(1):197-205. [PubMed:6706930]
  4. Taurog A: The mechanism of action of the thioureylene antithyroid drugs. Endocrinology. 1976 Apr;98(4):1031-46. [PubMed:1278093]
  5. Perrild H, Gruters-Kieslich A, Feldt-Rasmussen U, Grant D, Martino E, Kayser L, Delange F: Diagnosis and treatment of thyrotoxicosis in childhood. A European questionnaire study. Eur J Endocrinol. 1994 Nov;131(5):467-73. [PubMed:7952157]
  6. Orgiazzi J, Millot L: [Theoretical aspects of the treatment with antithyroid drugs]. Ann Endocrinol (Paris). 1994;55(1):1-5. [PubMed:7528484]
  7. Nakashima T, Taurog A: Rapid conversion of carbimazole to methimazole in serum; evidence for an enzymatic mechanism. Clin Endocrinol (Oxf). 1979 Jun;10(6):637-48. [PubMed:476986]
  8. Humar M, Dohrmann H, Stein P, Andriopoulos N, Goebel U, Roesslein M, Schmidt R, Schwer CI, Loop T, Geiger KK, Pahl HL, Pannen BH: Thionamides inhibit the transcription factor nuclear factor-kappaB by suppression of Rac1 and inhibitor of kappaB kinase alpha. J Pharmacol Exp Ther. 2008 Mar;324(3):1037-44. Epub 2007 Nov 30. [PubMed:18055877]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
References
  1. Ayub M, Levell MJ: Structure-activity relationships of the inhibition of human placental aromatase by imidazole drugs including ketoconazole. J Steroid Biochem. 1988 Jul;31(1):65-72. [PubMed:3398530]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:36