Temozolomide

Base Information

• Chemical Name: Temozolomide
• CAS No.: 85622-93-1
• Molecular Formula: C6H6N6O2
• Molecular Weight: 194.153
• Hs Code.: 29339900
• European Community (EC) Number: 630-358-9
• NSC Number: 759883,362856
• UNII: YF1K15M17Y
• DSSTox Substance ID: DTXSID5043714
• Nikkaji Number: J171.234I
• Wikipedia: Temozolomide
• Wikidata: Q425088
• NCI Thesaurus Code: C1244
• RXCUI: 37776
• Metabolomics Workbench ID: 43133
• ChEMBL ID: CHEMBL810
• Mol file: 85622-93-1.mol

Synonyms:8-carbamoyl-3-methylimidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one;CCRG 81045;CCRG-81045;CCRG81045;M and B 39831;M and B-39831;M and B39831;methazolastone;NSC 362856;NSC-362856;NSC362856;Temodal;Temodar;temozolomide;temozolomide hexyl ester;TMZ Bioshuttle;TMZ-Bioshuttle;TMZA-HE

Chemical Property of Temozolomide

Chemical Property:

• Appearance/Colour: Off-white to light-pink crystalline solid
• Melting Point: 212 °C dec.
• Boiling Point: 526.6 °C at 760 mmHg
• PKA: 14.77±0.20(Predicted)
• Flash Point: 272.3 °C
• PSA: 108.17000
• Density: 1.97 g/cm³
• LogP: -1.37780
• Storage Temp.: 2-8°C
• Solubility.: DMSO: soluble10mg/mL, clear
• XLogP3: -1.1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 1
• Exact Mass: 194.05522346
• Heavy Atom Count: 14
• Complexity: 315

Purity/Quality:

98% ^*data from raw suppliers

Temozolomide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T, Xi
• Hazard Codes: T,Xi
• Statements: 45-46-60-61-22-36/37/38
• Safety Statements: 24/25-45-36/37-26-53-36

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antineoplastic Agents, Alkylating Agents
• Canonical SMILES: CN1C(=O)N2C=NC(=C2N=N1)C(=O)N
• Recent ClinicalTrials: Veliparib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Malignant Glioma Without H3 K27M or BRAFV600 Mutations
• Recent EU Clinical Trials: Pilot safety study of neoadjuvant radiotherapy in patients with glioblastoma.
• Recent NIPH Clinical Trials: A Study of Abemaciclib (LY2835219) in Combination With Temozolomide and Irinotecan and Abemaciclib in Combination With Temozolomide in Children and Young Adult Participants With Solid Tumors
• Uses: Antineoplastic agents. Spontaneous and rapid degradation and produce the active metabolite MTIC in vivo, yielding anti-tumor effect. Imidazotetrazine alkylating agent. An antineoplastic. inhibits cancer cells similar to paclitaxel effective against paclitaxel-resistant tumours An apoptosis inducer which causes arrest at the G2/M cell cycle checkpoint. Temozolomide has been used for analyzing drug resistance mechanisms in glioblastoma cell lines15,16.
• Description: Temozolomide was launched for the first time in the UK for the treatment of patients with glioblastoma multiforme showing recurrence or progression after standard therapy. It can be considered as a cyclic variant of highly reactive triazenes producing a cascade of ionic or radical antitumoral species. Temozolamide is a 3-methyl analog of mitozolomide and was shown to be converted to cytotoxic triazene MCTIC. It can be prepared in 2 steps from 5- aminoimidazole-4-carboxamide by diazotization then cyclization with methylisocyanate. Mechanistically, the depletion of O6-alkylguanine-DNA alkyltransferase (OGAT) in cells or tumors was shown to be correlated with the cytotoxicity of temozolomide which is a potent inhibitor of this enzyme involved in DNA repair activity. Further approval applications for the treatment of other malignant gliomas such as relapsed anaplastic astrocytoma, advanced metastatic melanoma were submitted.
• Therapeutic Function: Antineoplastic
• Clinical Use: This imidazolotetrazine derivative is administered orally in capsule form for the treatment of glioblastoma multiforme or in patients with anaplastic astrocytoma who have not responded to procarbazine or the nitrosoureas.

Technology Process of Temozolomide

There total 29 articles about Temozolomide which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.6%

C12H11N7O5 → temozolomide (85622-93-1)

Guidance literature:

In N,N-dimethyl-formamide; at 50 ℃; Temperature; Solvent;

Reference yield: 98.0%

methyl isocyanate (624-83-9) + 5-diazoimidazole-4-carboxamide (7008-85-7) → temozolomide (85622-93-1)

Guidance literature:

In dichloromethane; at 25 ℃; for 480h;

DOI:10.1021/jm00368a016

Reference yield: 92.0%

ethyl 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylate → temozolomide (85622-93-1)

Guidance literature:

With ammonium hydroxide; copper(II) sulfate; at 100 ℃; for 6h; Reagent/catalyst; Temperature;

upstream raw materials:

methyl isocyanate

5-diazoimidazole-4-carboxamide

(8-Carbamoyl-4-oxo-imidazo[5,1-d][1,2,3,5]tetrazin-3-yl)-acetic acid 2-thioxo-2H-pyridin-1-yl ester

dimethyl sulfate

Downstream raw materials:

3-methyl-8-(4-phenyloxazol-2-yl)imidazo[5,1-d][1,2,3,5]tetrazin-4(3H)-one

3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-[N-(p-dimethylamino)phenyl]carboxamide hydrochloride

3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-[N-(p-diethylamino)phenyl]carboxamide hydrochloride

(3-methyl 4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carbonyl)-carbamic acid-4-isopropylidene cyclohex-1-enylmethyl ester

Refernces

• 1、 Laszcz, Marta,Kubiszewski, Marek,Jedynak, Lukasz,Kaczmarska, Monika,Kaczmarek, Lukasz,Luniewski, Wojciech,Gabarski, Krzysztof,Witkowska, Anna,Kuziak, Krzysztof,Malinska, Maura. "Identification and physicochemical characteristics of temozolomide process-related impurities". . p. 15344 - 15356. Retrieved 2013.
• 2、 -. "Temozolomide intermediate compound IV". . . Retrieved 2021/10/13.
• 3、 -. "PROCESS FOR PREPARING HIGHLY PURE TEMOZOLOMIDE". Page/Page column 17. . Retrieved 2020/10/18.