14223-47-3

Upstream product

• 10349-38-9 p-methoxyphenylisonitrile 
• 64-18-6 formic acid 
• 104-94-9 4-methoxy-aniline 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 506-80-9 carbon diselenide 

Downstream Products

• 40833-30-5 1-o-Chlorbenzoyl-4-(p-anisyl)-selenosemicarbazid 
• 85413-25-8 1-(4-Methoxy-phenyl)-3-thioacetyl-selenourea 
• 85413-26-9 1-(4-Methoxy-phenyl)-3-thiobenzoyl-selenourea 
• 1125526-65-9 N-(4-methoxyphenyl)-6-methyl-1H-benzo[d]imidazol-2-amine 
• 1049988-97-7 N-(4-methoxyphenyl)-6-chloro-1H-benzo[d]imidazol-2-amine 
• 1231894-17-9 1-(2-aminophenyl)-3-(4-methoxyphenyl) selenourea 
• 86601-29-8 N-(4-methoxyphenyl)-1H-benzo[d]imidazol-2-amine 
• 86601-36-7 N-(4-methoxyphenyl)-6-nitro-1H-benzo[d]imidazol-2-amine 
• 1247025-50-8 6-chloro-N-(4-methoxyphenyl)benzo[d]oxazol-2-amine 

Relevant academic research and scientific papers

Synthesis and leishmanicidal activity of novel urea, thiourea, and selenourea derivatives of diselenides

A novel series of thirty-one N-substituted urea, thiourea, and selenourea derivatives containing diphenyldiselenide entities were synthesized, fully characterized by spectroscopic and analytical methods, and screened for their in vitro leishmanicidal activities. The cytotoxic activity of these derivatives was tested against Leishmania infantum axenic amastigotes, and selectivity was assessed in human THP-1 cells. Thirteen of the synthesized compounds showed a significant antileishmanial activity, with 50% effective concentration (EC50) values lower than that for the reference drug miltefosine (EC50, 2.84 M). In addition, the derivatives 9, 11, 42, and 47, with EC50 between 1.1 and 1.95 M, also displayed excellent selectivity (selectivity index ranged from 12.4 to 22.7) and were tested against infected macrophages. Compound 11, a derivative with a cyclohexyl chain, exhibited the highest activity against intracellular amastigotes, with EC50 values similar to those observed for the standard drug edelfosine. Structure-activity relationship analyses revealed that N-aliphatic substitution in urea and selenourea is recommended for the leishmanicidal activity of these analogs. Preliminary studies of the mechanism of action for the hit compounds was carried out by measuring their ability to inhibit trypanothione reductase. Even though the obtained results suggest that this enzyme is not the target for most of these derivatives, their activity comparable to that of the standards and lack of toxicity in THP-1 cells highlight the potential of these compounds to be optimized for leishmaniasis treatment.

Bis-Selenoureas for Anion Binding: A 1H NMR and Theoretical Study

The anion binding ability of a family of bis-selenoureas L1-L3 obtained by the reaction of 1,3-bis(aminomethyl)-benzene and phenylisoselenocyanate, p-methoxyphenylisoselenocyanate and naphtylisoselenocyanate, for L1, L2, and L3, respectively, has been tested and compared to that of previously described bis-urea analogues. Results suggest that the introduction of selenium leads to an increase in the acidity of the urea NH hydrogen atoms, and therefore to a stronger affinity (more than three-fold higher) towards anion species, in particular dihydrogen phosphate, in DMSO-d6. Theoretical calculations allowed for the optimization of the adducts receptors corroborating the experimental results.

Novel 1,3,4-Selenadiazole-Containing Kidney-Type Glutaminase Inhibitors Showed Improved Cellular Uptake and Antitumor Activity

Kidney-type glutaminase [KGA/isoenzyme glutaminase C (GAC)] is becoming an important tumor metabolism target in cancer chemotherapy. Its allosteric inhibitor, CB839, showed early promise in cancer therapeutics but limited efficacy in in vivo cancer models. To improve the in vivo activity, we explored a bioisostere replacement of the sulfur atom in bis-2-(5-phenylacetamido-1,2,4-thiadiazol)ethyl sulfide and CB839 analogues with selenium using a novel synthesis of the selenadiazole moiety from carboxylic acids or nitriles. The resulting selenadiazole compounds showed enhanced KGA inhibition, more potent induction of reactive oxygen species, improved inhibition of cancer cells, and higher cellular and tumor accumulation than the corresponding sulfur-containing molecules. However, both CB839 and its selenium analogues show incomplete inhibition of the tested cancer cells, and a partial reduction in tumor size was observed in both the glutamine-dependent HCT116 and aggressive H22 liver cancer xenograft models. Despite this, tumor tissue damage and prolonged survival were observed in animals treated with the selenium analogue of CB839.

Thermal stability and decomposition of urea, thiourea and selenourea analogous diselenide derivatives

The fusion and thermal decomposition of thirty-three diselenide compounds with a urea, thiourea or selenourea group linked with different aliphatic or aromatic substituents have been studied by thermogravimetry, differential scanning calorimetry and mass spectrometry in order to perform comparative thermal stability studies among analogs. A relationship has been found between stability and a series of effects which occur in the compound structures. Analysis of the thermal data indicated that: (a) in general, compounds with a urea or selenourea group are more stable than those with a thiourea group; (b) no difference in stability exists when an aromatic or aliphatic group is linked to the thiourea group but when linked to the urea or selenourea groups, stability does differ; (c) selenourea compounds with aliphatic chain are the most unstable; and (d) the nature of the substituent located on the benzyl ring has no effects on thermal stability. Therefore, criteria for the selection of substituents can be established in order to improve the stability of these drugs. In addition, the mass spectral fragmentation in comparison with thermal analytical data helps in confirming the thermal behavior of the compounds.

Selenoureido-iminosugars: A new family of multitarget drugs

Herein we report the synthesis of N-alkylated deoxynojirimycin derivatives decorated with a selenoureido motif at the hydrocarbon tether as an example of unprecedented multitarget agents. Title compounds were designed as dual drugs for tackling simultaneously the Gaucher disease (by selective inhibition of β-glucosidase, Ki= 1.6–5.5 μM, with improved potency and selectivity compared to deoxynojirimycin) and its neurological complications (by inhibiting AChE, Kiup to 5.8 μM). Moreover, an excellent mimicry of the selenoenzyme glutathione peroxidase was also found for the catalytic scavenging of H2O2(Kcat/Kuncatup to 640) using PhSH as a cofactor, with improved activity compared to known positive controls, like (PhSe)2and ebselen; therefore, such compounds are also excellent scavengers of peroxides, an example of reactive oxygen species present at high concentrations in patients of Gaucher disease and neurological disorders.

"On water": Efficient iron-catalyzed cycloaddition of aziridines with heterocumulenes

In suspension: The reaction of aziridines with heterocumulenes in the presence of Fe(NO3)3×9 H2O in aqueous suspension provides access to functionalized five-membered heterocycles in good to high yields. This protocol has a wide substrate scope, is simple, and uses a nontoxic and cheap catalyst. Copyright

One-pot synthesis of 1-substituted-5-alkylselanyl-1H-tetrazoles from isoselenocyanates: Unexpected formation of N-alkyl-N-arylcyanamides and (Z)-Se-alkyl-N-cyano-N,N′-diarylisoselenoureas

1-Substituted-5-alkylsulfanyl-1H-tetrazoles are well known class of organic substances with various applications in medicinal chemistry or photographic industry. Their selenium analogues, 1-substituted-5-alkylselanyl-1H-tetrazoles are, however, much less explored because of the lack of suitable methods for their preparation. In this work we investigated the synthesis of 1-alkyl/aryl-5-alkylselanyl-1H-tetrazoles from synthetically available alkyl/arylisoselenocyanates. One-pot reactions of arylisoselenocyanates with sodium azide and alkylating agent led to the target 5-alkylselanyl-1-aryl-1H- tetrazoles but also to interesting side products, namely N-alkyl-N- arylcyanamides and (Z)-Se-alkyl-N-cyano-N,N′-diarylisoselenoureas. Nevertheless, when alkylisoselenocyanates were utilized as the substrates, the reactions led exclusively to the formation of 1-alkyl-5-alkylselanyl-1H- tetrazoles in good yields. This simple one-pot procedure brings new possibilities for the preparation of variously substituted selenium compounds. It also opens the way to further investigations of selenium isosteres of the widely utilized 5-thiotetrazole moiety in biomedical applications.

Efficient synthesis of 4H-benzo[d][1,3]oxazin-4-ones from anthranilic acids and aryl isoselenocyanates

A synthesis in good to excellent yields of 23 4H-benzo[d][1,3]oxazin-4- ones, 18 of which are novel, from monosubstituted anthranilic acids and variously substituted phenyl isoselenocyanates without using any harsh reagents has been developed. The Se powder precipitated during the reaction could be efficiently recycled for the preparation of the aryl isoselenocyanates.

Synthesis of sugar-derived isoselenocyanates, selenoureas, and selenazoles

Aryl, alkyl, and sugar-derived isoselenocyanates were prepared by a one-pot procedure starting from the corresponding formamides, using triphosgene as a dehydrating agent, triethylamine, and black selenium powder. The preparation of sugar selenoureas by coupling of O-protected sugar-derived isoselenocyanates with different amines, and by coupling of unprotected glycopyranosyl amines with phenyl isoselenocyanate was also accomplished. The synthesis of a glucopyranos-2-yl-selenazole starting from O-protected 2-amino-2-deoxy-d-glucose by coupling with benzoyl isoselenocyanate, Se-alkylation with phenacyl bromide, and acid-catalyzed dehydration is also reported. Unprotected N-(β-d-glucopyranosyl)-N′-phenylselenourea was transformed into a 1,2-trans-fused bicyclic isourea upon treatment with aqueous hydrogen peroxide; the same isourea was prepared by a one-pot three-step procedure from β-d-glycopyranosylamine by thiophosgenation, coupling with aniline, and HgO-mediated desulfurization.

Selenium-containing heterocycles from iso-selenocyanates: Synthesis of 2-arylamino-selenazolo[5,4-b]pyridines

The reaction of 3-amino-2-chloropyridine (4) with aryl isoselenocyanates (2a-d) in refluxing 2-propanol gave the hydrochlorides of 2-arylaminoselenazolo[5,4-b]pyridines (7a-d) in good yield. The free bases (8a-d) were obtained after treatment with aqueous NaOH and recrystallization. A reaction mechanism via the intermediate selenourea derivatives (5) is most likely. The structure of the 2-phenylamino derivative (8a) has been established by X-Ray crystallography.