3532-31-8

Usage

Synthesis Reference(s)

Synthetic Communications, 13, p. 289, 1983 DOI: 10.1080/00397918308066978

InChI:InChI=1/C7H5N4O3/c8-10-9-7(12)5-2-1-3-6(4-5)11(13)14/h1-4,8H/q+1

Upstream product

• 6415-38-9 benzenediazonium sulphate 
• 618-94-0 3-nitrobenzoic acid hydrazide 
• 121-90-4 m-nitrobenzoic acid chloride 
• 13651-07-5 2,2-dibromo-1-(3-nitrophenyl)ethan-1-one 
• 99-61-6 3-nitro-benzaldehyde 
• 18312-48-6 potassium m-nitrobenzoate 
• 121-92-6 3-nitrobenzoic acid 
• 618-95-1 methyl 3-nitrobenzoate 

Downstream Products

• 13141-83-8 1-(3-nitrophenyl)-3-(pyridin-2-yl)urea 
• 50610-66-7 N-acetyl-N'-(3-nitro-phenyl)-urea 
• 2189-61-9 (3-nitro-phenyl)-carbamic acid methyl ester 
• 91716-03-9 (3-nitro-phenyl)-carbamic acid propyl ester 
• 68621-24-9 (3-nitro-phenyl)-carbamic acid-(3,4-dimethyl-phenyl ester) 
• 29639-03-0 (3-nitro-phenyl)-carbamic acid-(4-nitro-phenyl ester) 
• 50686-02-7 (3-nitro-phenyl)-carbamic acid p-tolyl ester 
• 75004-30-7 (3-nitro-phenyl)-carbamic acid tert-pentyl ester 
• 50686-04-9 (3-nitro-phenyl)-carbamic acid-(4-bromo-phenyl ester) 
• 92491-59-3 (3-nitro-phenyl)-carbamic acid isobutyl ester 
• 92848-37-8 (3-nitro-phenyl)-carbamic acid pentyl ester 

Relevant academic research and scientific papers

Prodrugs for nitroreductase based cancer therapy-4: Towards prostate cancer targeting: Synthesis of N-heterocyclic nitro prodrugs, Ssap-NtrB enzymatic activation and anticancer evaluation

In this study, various N-heterocyclic nitro prodrugs (NHN1-16) containing pyrimidine, triazine and piperazine rings were designed and synthesized. The final compounds were identified using FT-IR, 1H NMR, 13C NMR as well as elemental analyses. Enzymatic activities of compounds were conducted by using HPLC analysis to investigate the interaction of substrates with Ssap-NtrB nitroreductase enzyme. MTT assay was performed to evaluate the toxic effect of compounds against Hep3B and PC3 cancer cell lines and healthy HUVEC cell. It was observed that synthesized compounds NHN1-16 exhibited different cytotoxic profiles. Pyrimidine derivative NHN3 and triazine derivative NHN5 can be good drug candidates for prostate cancer with IC50 values of 54.75 μM and 48.9 μM, respectively. Compounds NHN6, NHN10, NHN12, NHN14 and NHN16 were selected as prodrug candidates because of non-toxic properties against three different cell models. The NHN prodrugs and Ssap-NtrB combinations were applied to SRB assay to reveal the prodrug capabilities of these selected compounds. SRB screening results showed that the metabolites of all selected non-toxic compounds showed remarkable cytotoxicity with IC50 values in the range of 1.71–4.72 nM on prostate cancer. Among the tested compounds, especially piperazine derivatives NHN12 and NHN14 showed significant toxic effect with IC50 values of 1.75 nM and 1.79 nM against PC3 cell compared with standart prodrug CB1954 (IC50: 1.71 nM). Novel compounds NHN12 and NHN14 can be considered as promising prodrug candidates for nitroreductase-prodrug based prostate cancer therapy.

Discovery of N-phenyl-(2,4-dihydroxypyrimidine-5-sulfonamido) phenylurea-based thymidylate synthase (TS) inhibitor as a novel multi-effects antitumor drugs with minimal toxicity

Thymidylate synthase (TS) is a hot target for tumor chemotherapy, and its inhibitors are an essential direction for anti-tumor drug research. To our knowledge, currently, there are no reported thymidylate synthase inhibitors that could inhibit cancer cell migration. Therefore, for optimal therapeutic purposes, combines our previous reports and findings, we hope to obtain a multi-effects inhibitor. This study according to the principle of flattening we designed and synthesized 18 of N-phenyl-(2,4-dihydroxypyrimidine-5-sulfonamido)phenyl urea derivatives as multi-effects inhibitors. The biological evaluation results showed that target compounds could significantly inhibit the hTS enzyme, BRaf kinase and EGFR kinase activity in vitro, and most of the compounds had excellent anti-cell viability for six cancer cell lines. Notably, the candidate compound L14e (IC50 = 0.67 μM) had the superior anti-cell viability and safety to A549 and H460 cells compared with pemetrexed. Further studies had shown that L14e could cause G1/S phase arrest then induce intrinsic apoptosis. Transwell, western blot, and tube formation results proved that L14e could inhibit the activation of the EGFR signaling pathway, then ultimately achieve the purpose of inhibiting cancer cell migration and angiogenesis in cancer tissues. Furthermore, in vivo pharmacology evaluations of L14e showed significant antitumor activity in A549 cells xenografts with minimal toxicity. All of these results demonstrated that the L14e has the potential for drug discovery as a multi-effects inhibitor and provides a new reference for clinical treatment of non-small cell lung cancer.

Visible Light-Induced Regioselective Cycloaddition of Benzoyl Azides and Alkenes to Yield Oxazolines

Visible light catalysis allows the regioselective synthesis of oxazolines in high yields. The mild photosensitized manifold leverages the intermolecular formation of oxazolines with a wide functional group tolerance on both benzoyl azides and alkenes part

Synthesis of Amines, Carbamates and Amides by Multi-Step Continuous Flow Synthesis

We report the continuous flow synthesis of acyl azides in various continuous flow systems and demonstrate that liquid–liquid separation may be incorporated to prepare anhydrous solutions of the acyl azide, which may be subsequently reacted with appropriate nucleophiles to prepare amines, carbamates and amides within a fully integrated multi-step process in high yields (> 80 %). Interesting effects were also observed when preparing carbamates with long chain alcohols, whereby as the chain length of the alcohol increased the products could be made in high yield even without incorporation of the liquid–liquid separation module.

Direct and facile synthesis of acyl azides from carboxylic acids using the trichloroisocyanuric acid-triphenylphosphine system

A mild, efficient, and practical method for the one-step synthesis of acyl azides from carboxylic acids using a safe and inexpensive mixed reagent, trichloroisocyanuric acid-triphenylphosphine, is described.

Ir(III)-catalyzed mild C-H amidation of arenes and alkenes: An efficient usage of acyl azides as the nitrogen source

Reported herein is the development of the Ir(III)-catalyzed direct C-H amidation of arenes and alkenes using acyl azides as the nitrogen source. This procedure utilizes an in situ generated cationic half-sandwich iridium complex as a catalyst. The reaction takes place under very mild conditions, and a broad range of sp2 C-H bonds of chelate group-containing arenes and olefins are smoothly amidated with acyl azides without the intervention of the Curtius rearrangement. Significantly, a wide range of reactants of aryl-, aliphatic-, and olefinic acyl azides were all efficiently amidated with high functional group tolerance. Using the developed approach, Z-enamides were readily accessed with a complete control of regio- and stereoselectivity. The developed direct amidation proceeds in the absence of external oxidants and releases molecular nitrogen as a single byproduct, thus offering an environmentally benign process with wide potential applications in organic synthesis and medicinal chemistry.

FeCl36H2O-Catalyzed acceleration of the acylation of sodium azide with n-acylbenzotriazoles

Catalyzed by ferric chloride hexahydrate (FeCl36H2O), the acylation of sodium azide with N-acylbenzotriazoles was greatly accelerated in a mixed solvent of acetone and water. Thus, good to excellent yields of a variety of acyl azides were obtained at room temperature in a short time. Furthermore, because of the complete conversion of N-acylbenzotriazoles and the easy removal of the by-product, purification by column chromatography was no longer required, which made the protocol suitable for large-scale preparation.

An 'inside-out' approach to suramin analogues

An approach to the synthesis of suramin analogues has been realised, which avoids synthetic problems associated with conventional routes. The use of isobutyl ester protecting groups for sulfonic acids was crucial to the success of the strategy, because these were able to be cleanly deprotected with sodium iodide, yielding the sodium salts of the corresponding sulfonic acids.

Direct conversion of aldehydes to acyl azides using tert-butyl hypochlorite

A general method, for the direct conversion of aldehydes to acyl azides using tert-butyl hypochlorite and sodium azide is described. The method is simple and occurs under mild conditions.

Synthesis of acyl azides using the Vilsmeier complex

A facile synthesis of substituted cinnamoyl and benzoyl azides starting from their respective acids using DMF and POCl3 in the presence of sodium azide is reported.