60940-33-2

Upstream product

• 60940-55-8 2-benzyl-3-chloro-benzo[d]isoselenazolium; chloride 
• 106663-84-7 2,2‘-diselenobis(N-phenylbenzamide) 
• 1441-85-6 2-(chloroseleno)benzoyl chloride 
• 100-46-9 benzylamine 
• 3811-73-2 2-mercaptopyridine-1-oxide sodium salt 
• 73178-23-1 N-benzyl-2-iodobenzamide 
• 82082-50-6 N-benzyl-2-bromobenzamide 
• 7506-50-5 N-(o-chlorobenzoyl)benzylamine 
• 609-67-6 2-Iodobenzoyl chloride 
• 1485-70-7 N-benzylbenzamide 
• 98-88-4 benzoyl chloride 
• 134-20-3 2-carbomethoxyaniline 
• 2099-63-0 anthranilic acid hydrochloride 
• 7782-49-2 selenium 

Downstream Products

• 114744-70-6 S-(2-benzyl carbamoyl benzeneselenenyl)benzylmercaptan 
• 101563-08-0 S-(2-benzylcarbamoyl-phenylselenyl)-D-penicillamine 
• 106663-70-1 bis[2-(benzylcarbamoyl)phenyl] diselenide 
• 104473-79-2 2-benzyl-1,2-benzisoselenazol-3(2H)-one-Se-oxide 
• 60940-34-3 2-phenyl-1,2-benzoisoselenazol-3(2H)-one 
• 101563-10-4 S-(2-Benzylcarbamoyl-phenylselenyl)-L-cysteinethylester 
• 60940-40-1 benzo[d]isoselenazol-3-yl-benzyl-amine 
• 60940-55-8 2-benzyl-3-chloro-benzo[d]isoselenazolium; chloride 

Relevant academic research and scientific papers

Structure-Guided Discovery of the Novel Covalent Allosteric Site and Covalent Inhibitors of Fructose-1,6-Bisphosphate Aldolase to Overcome the Azole Resistance of Candidiasis

Fructose-1,6-bisphosphate aldolase (FBA) represents an attractive new antifungal target. Here, we employed a structure-based optimization strategy to discover a novel covalent binding site (C292 site) and the first-in-class covalent allosteric inhibitors

Inhibition of Pseudomonas aeruginosa Alginate Synthesis by Ebselen Oxide and Its Analogues

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that is frequently found in the airways of cystic fibrosis (CF) patients due to the dehydrated mucus that collapses the underlying cilia and prevents mucociliary clearance. During this life-long chronic infection, P. aeruginosa cell accumulates mutations that lead to inactivation of the mucA gene that results in the constitutive expression of algD-algA operon and the production of alginate exopolysaccharide. The viscous alginate polysaccharide further occludes the airways of CF patients and serves as a protective matrix to shield P. aeruginosa from host immune cells and antibiotic therapy. Development of inhibitors of alginate production by P. aeruginosa would reduce the negative impact from this viscous polysaccharide. In addition to transcriptional regulation, alginate biosynthesis requires allosteric activation by bis (3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) binding to an Alg44 protein. Previously, we found that ebselen (Eb) and ebselen oxide (EbO) inhibited diguanylate cyclase from synthesizing c-di-GMP. In this study, we show that EbO, Eb, ebsulfur (EbS), and their analogues inhibit alginate production. Eb and EbS can covalently modify the cysteine 98 (C98) residue of Alg44 and prevent its ability to bind c-di-GMP. However, P. aeruginosa with Alg44 C98 substituted with alanine or serine was still inhibited for alginate production by Eb and EbS. Our results indicate that EbO, Eb, and EbS are lead compounds for reducing alginate production by P. aeruginosa. Future development of these inhibitors could provide a potential treatment for CF patients infected with mucoid P. aeruginosa.

Synthesis of Benzoisoselenazolones via Rh(III)-Catalyzed Direct Annulative Selenation by Using Elemental Selenium

Isoselenazolone derivatives have attracted significant research interest because of their potent therapeutic activities and indispensable applications in organic synthesis. Efficient construction of functionalized isoselenazolone scaffolds is still challenging, and thus new synthetic approaches with improved operational simplicity have been of particular interest. In this manuscript, we introduce a rhodium-catalyzed direct selenium annulation by using stable and tractable elemental selenium. A series of benzamides as well as acrylamides were successfully coupled with selenium under mild reaction conditions, and the obtained isoselenazolones could be pivotal synthetic precursors for several organoselenium compounds. Based on the designed control experiments and X-ray absorption spectroscopy measurements, we propose an unprecedented selenation mechanism involving a highly electrophilic Se(IV) species as the reactive selenium donor. The reaction mechanism was further verified by a computational study.

1,2-BENZISOSELENAZOL-3(2H)-ONE AND 1,2-BENZISOTHIAZOL-3(2H)-ONE DERIVATIVES AS BETA-LACTAM ANTIBIOTIC ADJUVANTS

Provided herein are compositions and methods useful in the treatment of beta-lactam antibiotic resistant bacteria.

Investigation of synergistic antimicrobial effects of the drug combinations of meropenem and 1,2-benzisoselenazol-3(2H)-one derivatives on carbapenem-resistant Enterobacteriaceae producing NDM-1

The worldwide prevalence of NDM-1-producing bacteria has drastically undermined the clinical efficacy of the last line antibiotic of carbapenems, prompting a need to devise effective strategy to preserve their clinical value. Our previous studies have shown that ebselen can restore the efficacy of meropenem against a laboratory strain that produces NDM-1. Here we report the construction of a focused compound library of 1,2-benzisoselenazol-3(2H)-one derivatives which comprise a total of forty-six candidate compounds. The structure-activity relationship of these compounds and their potential to serve as an adjuvant to enhance the antimicrobial efficacy of meropenem against a collection of clinical NDM-1-producing carbapenem-resistant Enterobacteriaceae isolates was examined. Drug combination assays indicated that these derivatives exhibited synergistic antimicrobial activity when used along with meropenem, effectively restoring the activity of carbapenems against the resistant strains tested in a Galleria mellonella larvae in vivo infection model. The mode of inhibition of one compound, namely 11_a38, which was depicted when tested on the purified NDM-1 enzyme, indicated that it could covalently bind to the enzyme and displaced one zinc ion from the active site. Overall, this study provides a novel 1,2-benzisoselenazol-3(2H)-one scaffold that exhibits strong synergistic antimicrobial activity with carbapenems, and low cytotoxicity. The prospect of application of such compounds as carbapenem adjuvants warrants further evaluation.

SUBSTITUTED ISOSELENAZOLONE ANTI-INFLAMMATORY, ANTI-CANCER, CYTOPROTECTIVE, NEUROPROTECTIVE, AND ANTI-OXIDANT AGENTS

Compounds, compositions, and methods for the treatment of infections, inflammation, cancers, tinnitus, Meniere's disease, hearing loss, or bipolar disorder, or for providing cytoprotection against Clostridium difficile toxins, are disclosed.

Identification of methionine aminopeptidase 2 as a molecular target of the organoselenium drug ebselen and its derivatives/analogues: Synthesis, inhibitory activity and molecular modeling study

A collection of twenty-six organoselenium compounds, ebselen and its structural analogues, provided a novel approach for inhibiting the activity of human methionine aminopeptidase 2 (MetAP2). This metalloprotease, being responsible for the removal of the amino-terminal methionine from newly synthesized proteins, plays a key role in angiogenesis, which is essential for the progression of diseases, including solid tumor cancers. In this work, we discovered that ebselen, a synthetic organoselenium drug molecule with anti-inflammatory, anti-oxidant and cytoprotective activity, inhibits one of the main enzymes in the tumor progression pathway. Using three-step synthesis, we obtained twenty-five ebselen derivatives/analogues, ten of which are new, and tested their inhibitory activity toward three neutral aminopeptidases (MetAP2, alanine and leucine aminopeptidases). All of the tested compounds proved to be selective, slow-binding inhibitors of MetAP2. Similarly to ebselen, most of its analogues exhibited a moderate potency (IC50= 1–12 μM). Moreover, we identified three strong inhibitors that bind favorably to the enzyme with the half maximal inhibitory concentration in the submicromolar range.

Isoselenazolones as catalysts for the activation of bromine: Bromolactonization of alkenoic acids and oxidation of alcohols

Isoselenazolones were synthesized by a copper-catalyzed Se-N bond forming reaction between 2-halobenzamides and selenium powder. The catalytic activity of the various isoselenazolones was studied in the bromolactonization of pent-4-enoic acid. Isoselenazolone 9 was studied as a catalyst in several reactions: the bromolactonization of a series of alkenoic acids with bromine or N-bromosuccinimide (NBS) in the presence of potassium carbonate as base, the bromoesterification of a series of alkenes using NBS and a variety of carboxylic acids, and the oxidation of secondary alcohols to ketones using bromine as an oxidizing reagent. Mechanistic details of the isoselenazolone-catalyzed bromination reaction were revealed by 77Se NMR spectroscopic and ES-MS studies. The oxidative addition of bromine to the isoselenazolone gives the isoselenazolone(IV) dibromide, which could be responsible for the activation of bromine under the reaction conditions. Steric effects from an N-phenylethyl group on the amide of the isoselenazolone and electron-withdrawing fluoro substituents on the benzo fused-ring of the isoselenazolone appear to enhance the stability of the isoselenazolone as a catalyst for the bromination reaction.

Copper catalyzed/mediated synthetic methodology for ebselen and related isoselenazolones

Scope of the copper catalyzed/mediated selenium-nitrogen coupling reaction has been studied for the synthesis of isoselenazolones. It is noticed that the 2-chloro, 2-bromo-, and 2-iodo-aryl amides substrates can be exploited in the selenium-nitrogen coupling reaction by employing 25-100 mol % of CuI/1,10-phenanthroline (L) and potassium carbonate as a base in DMF. Furthermore, electron rich 2-chloro-arylamides also underwent selenium-nitrogen coupling reaction to give biologically important selenium-nitrogen heterocycles. Also, copper-catalyzed selenium-nitrogen coupling reaction has been meticulously applied for the synthesis of diaryl diselenides having methoxy, amine, and amide functionality from respective aryl iodides in the presence of stoichiometric amount of succinimide as an external Se-N coupling partner.

Crucial role of selenium in the virucidal activity of benzisoselenazol- 3(2h)-ones and related diselenides

Various N-substituted benzisoselenazol-3(2H)-ones and their non-seleniumcontaining analogues have been synthesized and tested against selected viruses (HHV-1, EMCV and VSV) to determine the extent to which selenium plays a role in antiviral activity. The data presented here show that the presence of selenium is crucial for the antiviral properties of benzisoselenazol-3(2H)-ones since their isostructural analogues having different groups but lacking selenium either did not show any antiviral activity or their activity was substantially lower. The open-chain analogues of benzisoselenazol- 3(2H)-ones-diselenides also exhibited high antiviral activity while selenides and disulfides were completely inactive towards model viruses.