3-methyl-4-oxo-3H,4H-imidazo[4,3-d][1,2,3,5]tetrazine-8-carboxamide

• ChemBase ID: 731
• Molecular Formular: C6H6N6O2
• Molecular Mass: 194.15084
• Monoisotopic Mass: 194.05522346
• SMILES: O=c1n2c(nnn1C)c(nc2)C(=O)N
• Canonical SMILES: NC(=O)c1ncn2c1nnn(c2=O)C
• InChI: InChI=1S/C6H6N6O2/c1-11-6(14)12-2-8-3(4(7)13)5(12)9-10-11/h2H,1H3,(H2,7,13)
• InChIKey: BPEGJWRSRHCHSN-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 3-methyl-4-oxo-3H,4H-imidazo[4,3-d][1,2,3,5]tetrazine-8-carboxamide
• IUPAC Traditional name: temozolomide; 3-methyl-4-oxo-3H,4H-imidazo[4,3-d][1,2,3,5]tetrazine-8-carboxamide
• Brand Name: Temodal; Temodar
• Synonyms: 3-Methyl-4-oxo-8-imidazolo[5,1-d][1,2,3,5]tetrazinecarboxamide; 4-Methyl-5-oxo-2,3,4,6,8-pentazabicyclo[4.3.0]nona-2,7,9-triene-9-carboxamide; 8-Carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one; Temozolomide; 3-Methyl-4-oxo-3,4-dihydroimidazo-[5,1-d][1,2,3,5]tetrazine-8-carboxamide; 3-methyl-4-oxo-3H,4H-imidazo[4,3-d][1,2,3,5]tetrazine-8-carboxamide; Temozolodida [Spanish]; Temozolomidum [Latin]; Temozolamide; Methazolastone; temozolomide; Temozolomide; 3,4-Dihydro-3-methyl-4-oxo-imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide; NSC 362856; Sch 52365; Temodal; Temodar; 3-Methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide; 3-甲基-4-氧代-8-咪唑并[5,1-d][1,2,3,5]四嗪甲酰胺; 4-甲基-5-氧代-2,3,4,6,8-五氮杂双环[4.3.0]壬基-2,7,9-三烯-9-甲酰胺; 8-氨甲酰-3-甲基咪唑[5,1-d]-1,2,3,5-四嗪-4(3H)-酮; 替莫唑胺

Database IDs

• CAS Number: 85622-93-1
• MDL Number: MFCD00866492
• PubChem SID: 46507934; 160964194
• PubChem CID: 5394

CALCULATED PROPERTIES

JChem

• Acid pKa: 10.51155
• H Acceptors: 5
• H Donor: 1
• LogD (pH = 5.5): -0.2825344
• LogD (pH = 7.4): -0.28223866
• Log P: -0.28253815
• Molar Refractivity: 47.8609 cm^3
• Polarizability: 16.084875 Å^3
• Polar Surface Area: 105.94 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -1.0
• LOG S: -1.58
• Solubility (Water): 5.09e+00 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; DMSO: >20 mg/mL; H2O: insoluble; Methanol
• Apperance: white powder; White to Off-White Solid
• Melting Point: >177°C (dec.)
• Hydrophobicity(logP): -0.811; -2.8

Safety Information

• Storage Condition: -20°C Freezer
• Storage Warning: IRRITANT
• RTECS: NJ5927050
• European Hazard Symbols: Toxic (T)
• German water hazard class: 3
• Risk Statements: 45-46-60-61-22-36/37/38
• Safety Statements: 53-26-36/37-45
• TSCA Listed: false
• GHS Pictograms: GHS07; GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H302-H315-H319-H335-H340-H350-H360; H302-H315-H319-H335-H350-H360
• GHS Precautionary statements: P201-P261-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; Eyeshields, Gloves, type P2 (EN 143) respirator cartridges
• Storage Temperature: 2-8°C

Pharmacology Properties

• Mechanism of Action: Alkylating agent

Product Information

• Purity: ≥98% (HPLC); ≥99.0% (HPLC); 95%; 95+%
• Grade: VETRANAL™, analytical standard
• Ignition Residue: ≤0.2%
• Loss on Drying: ≤0.5% loss on drying
• Application(s): Antineoplastic agent; Used for the treatment of glioblastoma multiforme
• Empirical Formula (Hill Notation): C6H6N6O2

DETAILS

DrugBank - DB00853

• Drug Groups: approved; investigational
• Description: Temozolomide (Temodar and Temodal) is an oral alkylating agent used for the treatment of refractory anaplastic astrocytoma -- a type of cancerous brain tumor. Temozolomide is not active until it is converted at physiologic pH to the active form, 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC).
• Indication: For the treatment of adult patients diagnosed with anaplastic astrocytoma whose disease has progressed after therapy with nitrosourea and procarbazine, as well as concomitantly with radiation therapy for treatment of newly diagnosed glioblastoma multiforme. Also used as maintenance therapy for glioblastoma multiforme.
• Pharmacology: Temozolomide is an imidazotetrazine deritave and an antineoplastic agent. It is a prodrug that has little to no pharmacological activity until it is hydrolyzed in vivo to 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC). After administration, temozolomide undergoes rapid, nonenzymatic hydrolysis at physiological pH to MTIC, which is the active form of the drug. MTIC is generated through the effect of water at the highly electropositive C4 position of temozolomide, causing the ring of temozolomide to open, release carbon dioxide, and generate MTIC.
• Affected Organisms: Humans and other mammals
• Absorption: Rapid and complete absorption in the gastrointestinal tract
• Half Life: Approximately 1.8 hours.
• Protein Binding: 15%
• Elimination: About 38% of the administered temozolomide total radioactive dose is recovered over 7 days: 37.7% in urine and 0.8% in feces.
• Distribution: * 0.4 L/kg
• Clearance: * 5.5 L/hr/m2
• References: Neyns B, Tosoni A, Hwu WJ, Reardon DA: Dose-dense temozolomide regimens: antitumor activity, toxicity, and immunomodulatory effects. Cancer. 2010 Jun 15;116(12):2868-77. [Pubmed] ; Wick W, Platten M, Weller M: New (alternative) temozolomide regimens for the treatment of glioma. Neuro Oncol. 2009 Feb;11(1):69-79. Epub 2008 Sep 4. [Pubmed] ; Villano JL, Seery TE, Bressler LR: Temozolomide in malignant gliomas: current use and future targets. Cancer Chemother Pharmacol. 2009 Sep;64(4):647-55. Epub 2009 Jun 19. [Pubmed] ; Meije Y, Lizasoain M, Garcia-Reyne A, Martinez P, Rodriguez V, Lopez-Medrano F, Juan RS, Lalueza A, Aguado JM: Emergence of cytomegalovirus disease in patients receiving temozolomide: report of two cases and literature review. Clin Infect Dis. 2010 Jun 15;50(12):e73-6. [Pubmed] ; Trinh VA, Patel SP, Hwu WJ: The safety of temozolomide in the treatment of malignancies. Expert Opin Drug Saf. 2009 Jul;8(4):493-9. [Pubmed] ; Yung WK: Temozolomide in malignant gliomas. Semin Oncol. 2000 Jun;27(3 Suppl 6):27-34. [Pubmed] ; Friedman HS, Kerby T, Calvert H: Temozolomide and treatment of malignant glioma. Clin Cancer Res. 2000 Jul;6(7):2585-97. [Pubmed] ; Mutter N, Stupp R: Temozolomide: a milestone in neuro-oncology and beyond? Expert Rev Anticancer Ther. 2006 Aug;6(8):1187-204. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - T2577

Frequently Asked Questions
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Biochem/physiol Actions
Temozolomide is a DNA methylating agent and drug resistance-modifying agent; anti-tumor and anti-angiogenic. Temozolomide induces G2/M arrest and apoptosis through adduction of a methyl group to O6 position of guanine in genomic DNA and functional inactivation of DNA repair protein O(6)-alkylguanine DNA alkyltransferase (AGT) in base excision repair (BER) pathway.

Sigma Aldrich - 76899

Legal Information
VETRANAL is a trademark of Sigma-Aldrich Co. LLC

Sigma Aldrich - 34219

Legal Information
VETRANAL is a trademark of Sigma-Aldrich Co. LLC

Toronto Research Chemicals - T017775

Imidazotetrazine alkylating agent. An antineoplastic.

REFERENCES

• Yung WK: Temozolomide in malignant gliomas. Semin Oncol. 2000 Jun;27(3 Suppl 6):27-34. Pubmed
• Neyns B, Tosoni A, Hwu WJ, Reardon DA: Dose-dense temozolomide regimens: antitumor activity, toxicity, and immunomodulatory effects. Cancer. 2010 Jun 15;116(12):2868-77. Pubmed
• Wick W, Platten M, Weller M: New (alternative) temozolomide regimens for the treatment of glioma. Neuro Oncol. 2009 Feb;11(1):69-79. Epub 2008 Sep 4. Pubmed
• Villano JL, Seery TE, Bressler LR: Temozolomide in malignant gliomas: current use and future targets. Cancer Chemother Pharmacol. 2009 Sep;64(4):647-55. Epub 2009 Jun 19. Pubmed
• Meije Y, Lizasoain M, Garcia-Reyne A, Martinez P, Rodriguez V, Lopez-Medrano F, Juan RS, Lalueza A, Aguado JM: Emergence of cytomegalovirus disease in patients receiving temozolomide: report of two cases and literature review. Clin Infect Dis. 2010 Jun 15;50(12):e73-6. Pubmed
• Trinh VA, Patel SP, Hwu WJ: The safety of temozolomide in the treatment of malignancies. Expert Opin Drug Saf. 2009 Jul;8(4):493-9. Pubmed
• Friedman HS, Kerby T, Calvert H: Temozolomide and treatment of malignant glioma. Clin Cancer Res. 2000 Jul;6(7):2585-97. Pubmed
• Mutter N, Stupp R: Temozolomide: a milestone in neuro-oncology and beyond? Expert Rev Anticancer Ther. 2006 Aug;6(8):1187-204. Pubmed
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