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Usage

Uses

Used in Pharmaceutical Industry:
Ethazolastone is used as a pharmaceutical compound for its enzyme inhibitory properties, which can be leveraged in the development of drugs targeting various medical conditions. Its potential applications in medicine are attributed to its ability to modulate enzymatic activities, offering a foundation for therapeutic interventions.
Used in Drug Development:
In the field of drug development, ethazolastone serves as a key component in the creation of novel therapeutic agents. Its unique cyclic structure and heteroatom composition provide a versatile platform for the design of drugs with specific biological activities, making it an invaluable asset in the advancement of medicinal chemistry.

InChI:InChI=1/C7H8N6O2/c1-2-13-7(15)12-3-9-4(5(8)14)6(12)10-11-13/h3H,2H2,1H3,(H2,8,14)

Upstream product

• 188612-55-7 5-amino-N 1-ethyl-1H-imidazole-1,4-dicarboxamide 
• 7008-85-7 5-diazoimidazole-4-carboxamide 
• 109-90-0 ethyl isocyanate 

Relevant academic research and scientific papers

Imidazotetrazines as Weighable Diazomethane Surrogates for Esterifications and Cyclopropanations

Diazomethane is one of the most versatile reagents in organic synthesis, but its utility is limited by its hazardous nature. Although alternative methods exist to perform the unique chemistry of diazomethane, these suffer from diminished reactivity and/or correspondingly harsher conditions. Herein, we describe the repurposing of imidazotetrazines (such as temozolomide, TMZ, the standard of care for glioblastoma) for use as synthetic precursors of alkyl diazonium reagents. TMZ was employed to conduct esterifications and metal-catalyzed cyclopropanations, and results show that methyl ester formation from a wide variety of substrates is especially efficient and operationally simple. TMZ is a commercially available solid that is non-explosive and non-toxic, and should find broad utility as a replacement for diazomethane.

Antitumor imidazo[5,1-d]-1,2,3,5-tetrazines: compounds modified at the 3-position overcome resistance in human glioblastoma cell lines

Synthetic routes to 3-substituted imidazo[5,1-d]-1,2,3,5-tetrazines structurally related to temozolomide were explored. Interaction of 4-diazoimidazole-5-carboxamide with an isocyanate afforded high product yields when the isocyanate was available in acceptable purity. Alternatively, alkylation of the nor-temozolomide anion afforded high yields of new imidazotetrazines. Several compounds, evaluated against a panel containing matched MGMT± glioma cell lines, showed equal inhibitory activity irrespective of MGMT status; the N3-propargyl-imidazotetrazine (10m) was prioritised as an alternative to temozolomide able to bypass drug-resistance mechanisms. In Taq polymerase assays 10m, like temozolomide and its ring-opened counterpart MTIC, alkylated DNA at clusters of three and five guanine residues; covalent modification of N-7 sites of guanine were detected in piperidine cleavage assays. Compound 10m did not cross-link DNA but induced double-strand breaks evidenced by γ-H2AX detection. Propargyl-substituted imidazotriazene (13g), showed comparable activity to 10m indicating that ring-opening of the bicyclic nucleus of novel imidazotetrazine is probably required for activity.

Antitumour imidazotetrazines. Part 36. Conversion of 5-aminoimidazole-4-carboxamide to imidazo[5,1-d][1,2,3,5]tetrazin-4(3H)-ones and imidazo[1,5-a][1,3,5]triazin-4(3H)-ones related in structure to the antitumour agents temozolomide and mitozolomide

Novel 3-substituted imidazo[5,1-d][1,2,3,5]tetrazinones 3 have been prepared by two routes: reaction of 5-diazoimidazole-4-carboxamide 2 and isocyanates, and nitrosative cyclisation of 5-amino-1-carbamoylimidazole-4-carboxamides 7. The latter cyclisations do not proceed efficiently when the 1-carbamoyl group bears an electron-donating alkyl group. 5-Amino-1-carbamoylimidazole-4-carboxamides 7 cyclise with triethyl orthoformate or triethyl orthobenzoate to yield imidazo[1,5-a][1,3,5]triazinones 15. A 1H NMR study of the decomposition of 8-carbamoyl-3-ethylimidazo[5,1-d][1,2,3,5]tetrazin-4(3H)-one 3c in deuteriated phosphate buffer has shown that its ethylating capacity is attenuated by the unproductive generation of ethene. This observation explains why the ethylimidazotetrazine possesses weaker antitumour properties than the clinically-used congener temozolomide 3a.

A new route to the antitumour drug temozolomide, but not thiotemozolomide

Interaction of 5-aminoimidazole-4-carboxamide with alkyl isocyanates yields N-substituted 1-carbamoylimidazoles which can be cyclised to imidazo[5,1-d][1,2,3,5]tetrazin-4(3H)-ones, including temozolomide 3a, on nitrosation; a similar reaction with methyl isothiocyanate, followed by nitrosation, affords the nitrosomethylamino derivative 11 of a new ring-system, imidazo[l,5-b][1,2,4]thiadiazole.