5-(dimethyltriaz-1-en-1-yl)-1H-imidazole-4-carboxamide

• ChemBase ID: 729
• Molecular Formular: C6H10N6O
• Molecular Mass: 182.1832
• Monoisotopic Mass: 182.09160897
• SMILES: c1(c(nc[nH]1)C(=O)N)/N=N/N(C)C
• Canonical SMILES: CN(/N=N/c1[nH]cnc1C(=O)N)C
• InChI: InChI=1S/C6H10N6O/c1-12(2)11-10-6-4(5(7)13)8-3-9-6/h3H,1-2H3,(H2,7,13)(H,8,9)/b11-10+
• InChIKey: FDKXTQMXEQVLRF-ZHACJKMWSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-(dimethyltriaz-1-en-1-yl)-1H-imidazole-4-carboxamide; 5-[(1E)-dimethyltriaz-1-en-1-yl]-1H-imidazole-4-carboxamide
• IUPAC Traditional name: dtic-dome (TN); dacarbazine
• Brand Name: Deticene
• Synonyms: NSC-45388; Dacatic; Deticene; 5-(3,3-Dimethyl-1-triazenyl)imidazole-4-carboxamide; Dacarbazine; 5-[3,3-Dimethyl-1-triazenyl]imidazole-4-carboxamide; Dacarbazino [INN-Spanish]; Dacarbazinum [INN-Latin]; DIC; DTIC; Dtic-Dome; ICDMT; Imidazole Carboxamide; ICDT; DTIE; Biocarbazine R; Dacarbazine

Database IDs

• CAS Number: 4342-03-4
• EC Number: 224-396-1
• MDL Number: MFCD00057167
• PubChem SID: 24893683; 160964192
• PubChem CID: 5353562

CALCULATED PROPERTIES

JChem

• Acid pKa: 5.890213
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): -0.5566359
• LogD (pH = 7.4): -1.3159575
• Log P: -0.42588896
• Molar Refractivity: 49.7106 cm^3
• Polarizability: 16.888016 Å^3
• Polar Surface Area: 99.73 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -0.32
• LOG S: -2.13
• Solubility (Water): 1.36e+00 g/l

PROPERTIES

Physical Property

• Solubility: 4220 mg/L; DMSO; Methanol
• Apperance: Off-White to Light Yellow Solid
• Melting Point: >205°C (dec); 202°C
• Hydrophobicity(logP): -1.6

Safety Information

• Storage Condition: -20°C; -20°C Freezer; 2-8°C, Protect from light
• RTECS: NI3950000
• European Hazard Symbols: Toxic (T)
• German water hazard class: 3
• Risk Statements: 45-46-20/21/22-36/37/38; R:45
• Safety Statements: 53-36/37/39-45; S:28-36/37/39-45-53
• GHS Pictograms: GHS07; GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H312-H315-H319-H332-H335-H350
• GHS Precautionary statements: P201-P261-P280-P305 + P351 + P338-P308 + P313
• Personal Protective Equipment: Eyeshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: DNA/RNA synthesis

Product Information

• Salt Data: Free Base

DETAILS

MP Biomedicals - 02157519

(5-[3,3-Dimethyl-1-triazenyl]imidazole-4-carboxamide; DTIC)

DrugBank - DB00851

• Drug Groups: approved
• Description: An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)
• Indication: For the treatment of metastatic malignant melanoma. In addition, dacarbazine is also indicated for Hodgkin's disease as a secondary-line therapy when used in combination with other antineoplastic agents.
• Pharmacology: Dacarbazine is a synthetic analog of naturally occurring purine precursor 5-amino-1H-imidazole-4-carboxamide (AIC). After intravenous administration of dacarbazine, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. Its disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours. 1 In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours. 1 The average cumulative excretion of unchanged DTIC in the urine is 40% of the injected dose in 6 hours. 1 DTIC is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations dacarbazine is not appreciably bound to human plasma protein.
• Toxicity: LD₅₀=350mg/kg (orally in mice)
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: Erratic, slow and incomplete
• Half Life: 5 hours
• Protein Binding: Less than 5%
• Elimination: Dacarbazine is subject to renal tubular secretion rather than glomerular filtration. In man, dacarbazine is extensively degraded. Besides unchanged dacarbazine, 5-aminoimidazole -4 carboxamide (AIC) is a major metabolite of dacarbazine excreted in the urine.
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1221

Research Area: Cancer
Biological Activity:
Dacarbazine(DTIC-Dome) is an antineoplastic chemotherapy drug used in the treatment of various cancers, among them malignant melanoma, Hodgkin lymphoma, sarcoma, and islet cell carcinoma of the pancreas. [1]Dacarbazine belongs to the family of chemicals known as alkylating agents. Dacarbazine alkylates and cross-links DNA during all phases of the cell cycle, resulting in disruption of DNA function, cell cycle arrest, and apoptosis. [2]Dacarbazine is normally administered by injection (a shot) or intravenous infusion (IV) under the immediate supervision of a doctor or nurse. [1]

Sigma Aldrich - D2390

Application
Dacarbazine is a triazine antineoplastic agent that is used for DNA methylation via formation of methyl adducts. It is used to treat metastatic malignant melanomas and Hodgkin′s when used in combination with other antineoplastic agents. It is used to induce apoptosis in human cells1. It has been used to induce hepatotoxicity in mice2.
Biochem/physiol Actions
Dacarbazine has significant activity against melanomas. It is a synthetic analog of naturally occurring purine precursor 5-amino-1H-imidazole-4-carboxamide (AIC). Dacarbazine appears to exert cytotoxic effects by acting as an alkylating agent, by inhibiting DNA synthesis as a purine analog, and by inducing apoptosis1. Dacarbazine is not cell cycle-phase specific.

Toronto Research Chemicals - D101400

Dacarbazine is used as an antineoplastic for treatment of malignant melanoma and sarcomas.

REFERENCES

• http://www.cancer.gov/drugdictionary/?CdrID=39768
• Shealy, et al.: Biochem. Pharmacol., 11, 674 (1962)
• Carter, et al.: Eur. J. Cancer, 8, 85 (1962)