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

• ChemBase编号: 731
• 分子式: C6H6N6O2
• 平均质量: 194.15084
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: 3-methyl-4-oxo-3H,4H-imidazo[4,3-d][1,2,3,5]tetrazine-8-carboxamide
• IUPAC传统名: temozolomide; 3-methyl-4-oxo-3H,4H-imidazo[4,3-d][1,2,3,5]tetrazine-8-carboxamide
• 商标名: Temodal; Temodar
• 别名: 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; 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

登记号

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

理论计算性质

JChem

• Acid pKa: 10.51155
• 质子受体: 5
• 质子供体: 1
• LogD (pH = 5.5): -0.2825344
• LogD (pH = 7.4): -0.28223866
• Log P: -0.28253815
• 摩尔折射率: 47.8609 cm^3
• 极化性: 16.084875 Å^3
• 极化表面积: 105.94 Å^2
• 可自由旋转的化学键: 1
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: -1.0
• LOG S: -1.58
• 溶解度: 5.09e+00 g/l

分子性质

理化性质

• 溶解度: DMSO; DMSO: >20 mg/mL; H2O: insoluble; Methanol
• 外观: white powder; White to Off-White Solid
• 熔点: >177°C (dec.)
• 疏水性(logP): -0.811; -2.8

安全信息

• 保存条件: -20°C Freezer
• 保存注意事项: IRRITANT
• RTECS编号: NJ5927050
• 欧盟危险性物质标志: 有毒(Toxic) (T)
• 德国WGK号: 3
• 危险公开号: 45-46-60-61-22-36/37/38
• 安全公开号: 53-26-36/37-45
• TSCA收录: false
• GHS危险品标识: GHS07; GHS08
• GHS警示词: Danger
• GHS危险声明: H302-H315-H319-H335-H340-H350-H360; H302-H315-H319-H335-H350-H360
• GHS警示性声明: P201-P261-P305 + P351 + P338-P308 + P313
• 个人保护装置: 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
• 保存温度: 2-8°C

药理学性质

• 生物活性机理: Alkylating agent

产品相关信息

• 纯度: ≥98% (HPLC); ≥99.0% (HPLC); 95%; 95+%
• 级别: VETRANAL™, analytical standard
• 燃烧残渣: ≤0.2%
• 干燥失重: ≤0.5% loss on drying
• 应用领域: Antineoplastic agent; Used for the treatment of glioblastoma multiforme
• Empirical Formula (Hill Notation): C6H6N6O2

详细说明

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
Live Chat and Frequently Asked Questions are available for this Product.
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

法律信息
VETRANAL 商标 Sigma-Aldrich Co. LLC

Sigma Aldrich - 34219

法律信息
VETRANAL 商标 Sigma-Aldrich Co. LLC

Toronto Research Chemicals - T017775

Imidazotetrazine alkylating agent. An antineoplastic.

参考文献

• 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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