60940-34-3

Basic information

• Product Name: Ebselen
• Synonyms: 2-phenyl-1,2-benzisoselenazol-;2-Phenyl-1,2-benzoselenazol-3-one;Harmokisane;2-Phenyl-1-selena-2-azaindan-3-one;DR-3305;RP-60931;Ebselen,99%;Ebselen2-Phenyl-benzo[d]isoselenazol-3-one
• CAS NO: 60940-34-3
• Molecular Formula: C₁₃H₉NOSe
• Molecular Weight: 274.18
• EINECS: 612-054-8
• Product Categories: Glutamate receptor
• Mol File: 60940-34-3.mol
• Article Data: 36

Chemical Properties

• Melting Point: 178-181 °C
• Boiling Point: 402.8 °C at 760 mmHg
• Flash Point: 197.4 °C
• Appearance: Yellow to beige/Crystalline Powder
• Vapor Pressure: 1.07E-06mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: Soluble in ethanol, methanol, acetone, acetonitrile.
• PKA: -0.40±0.20(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.
• Merck: 14,3486
• CAS DataBase Reference: Ebselen(CAS DataBase Reference)
• NIST Chemistry Reference: Ebselen(60940-34-3)
• EPA Substance Registry System: Ebselen(60940-34-3)

Safety Data

• Hazard Codes: T,N,Xi
• Statements: 23/25-33-50/53-36/37/38
• Safety Statements: 20/21-28-45-60-61-28A-36/37-26
• RIDADR: UN 3283 6.1/PG 3
• WGK Germany: 3
• RTECS: DE4140750
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 60940-34-3(Hazardous Substances Data)

Usage

Description

Ebselen is one of the selenium-containing anti-inflammatory drugs.In 2003, Rocha and co-workers identified diselenides as a new class of antiinflammatory agents.In 2014, Nogueira and co-workers reported the synthesis and anti-inflammatory activity of salicyclic-based diselenides and selenocynates.Recently, Wilhelm and co-workers identified 4-phenylselenyl-7-chloroquinoline 270 as a potent antiinflammatory compound.

Chemical Properties

yellow to beige crystalline powder

Uses

Different sources of media describe the Uses of 60940-34-3 differently. You can refer to the following data:
1. antioxidant, lipoxygenase inhibitor, inhibits oxidation of LDL
2. 2-Phenyl-1,2-benzoselenazol-3-one acts as an antiinfammatory compounds,, in addition to that it acts as a modulator of KVβ subunits.
3. Ebselen is a lipid-soluble organoselenium compound. Numerous in vivo experiments have demonstrated that ebselen is able to inhibit both vasospasm and tissue damage in cerebral stroke/ischemia animal models (i.e. rat, mice, guinea pig and dog).For example, ebselen has been shown to provide significant protection against ischemic damage in both gray and white matter, and in the ventral posterior nucleus of rodent brains.Additionally, administration of ebselen in gerbils significantly reduces neuronal death induced by ischemia and reperfusion in the hippocampal CA1 region.It has been reported that ebselen inhibits inositol monophosphatase and acts as a safe treatment for bipolar disorder. The optimal GPx-like activity of ebselen was observed at neutral or nearphysiological pH (7.4), and the activity of ebselen was barely detected in acidic medium.During ischemia, brain pH falls rapidly within the first 5 min from 7.0 to 6.2, which is not optimal for ebselen's GPx-like activity.Meanwhile, since ebselen has shown promising activity in the treatment of stroke, it seems that GPx-like activity of ebselen in the brain may not occur.Thus, the enzymatic reduction of ebselen by TrxR might be the main contribution to its antioxidant property during ischemia. Unlike inorganic and aliphatic selenium compounds, ebselen does not liberate the selenium moiety, which remains within the ring structure. Subsequent metabolism involves methylation, glucuronidation and hydroxylation. Additionally, ebselen could also inhibit enzymes such as lipoxygenases, nitric oxide synthases, nitrogen oxides, protein kinase C and H1/K1-ATPase. Besides the relationship with redox systems, another neuroprotective mechanism of ebselen is involved in controlling the expression of gaminobutyric acid shunt enzymes to supply the tricarboxylic acid cycle, and significantly inhibiting acetylcholinesterase activity,demonstrating its engagement in the metabolic system.

Definition

ChEBI: A benzoselenazole that is 1,2-benzoselenazol-3-one carrying an additional phenyl substituent at position 2. Acts as a mimic of glutathione peroxidase.

Reactions

Ebselen is a substrate for mammalian TrxR and can be converted to ebselen selenol by consuming NADPH.The reduction reaction acts with an apparent KM value of 2.5 mM and a kcat of 588 min-1. Oxidants such as H2O2 react with ebselen selenol to produce ebselen selenenic acid (EbSeOH), and spontaneously produce H2O and ebselen to form a redox cycling mechanism for ebselen. Upon the addition of Trx to TrxR, NADPH and ebselen, the reaction rate increases several-fold. This may be achieved by a very fast oxidation of reduced Trx by ebselen at a reaction rate constant42107 M1 s1.This rate is orders of magnitude faster than the reaction of reduced Trx with a substrate such as insulin disulfides. Thus, ebselen can compete with disulfide substrates for the reduction by Trx. These results indicate that ebselen can serve as a mediator in the redox environment via the Trx system.

General Description

Ebselen is a sympathomimetic amine.

Biochem/physiol Actions

Ebselen, a glutathione-peroxidase-mimic, elicits anti-inflammatory activity. It also has anti-atherosclerotic functionality. Ebselen displays antibacterial action on) multidrug-resistant Staphylococcus aureus (MRSA) infections and could be a potential therapeutic target for treating MRSA based skin infection. It is regarded as neuroprotective agent and elicits chemopreventive functionality in inflammation-associated carcinogenesis.

Clinical Use

Ebselen and its analogs have also been shown to be inhibitors of Bacillus anthracis TrxR. The ebselen analogs displayed antibacterial activity on Bacillus subtilis, S. aureus, Bacillus cereus and M. tuberculosis. There existed a high resistance barrier for the bacteria to develop ebselen-resistant strains and isolating resistant mutants was found to be difficult and, ultimately, unsuccessful.28 The reason for the difficulty of developing ebselen-resistant bacteria may be because ebselen has exerted a multiple drug-target mechanism, although the exact mechanism is not yet known. In addition to the thioredoxin and GSH systems, ebselen has been reported to have some other potential targets in bacteria, which may help it to overcome the bacterial drug resistance. Ebselen was identified as an inhibitor of diguanylate cyclases by a high-throughput screening in another study by covalent binding to Cys residues.29 This may block the cyclic-di-GMP signaling pathway, regulating biofilm formation, flagella-mediated motility in Pseudomonas aeruginosa, and thus its pathogenesis. Ebselen was identified as an inhibitor of the cysteine protease domain (CPD) in the Clostridium difficile major virulence factor toxin B (TcdB) by another high-throughput screening study. A CPD can bind with one or two ebselen molecules with a covalent modification probably occurring at the active site Cys. The treatment of ebselen blocked the toxic effects of TcdB and the pathology of C. difficile infection in mice.30 Another study also indicated that ebselen is a potent inhibitor of the M. tuberculosis Ag85 complex by binding covalently to a Cys residue (C209) located near the Ag85C active site, which is central to the synthesis of major components of the inner and outer leaflets of the mycobacterial outer membrane.

References

1) Schewe et al. (1995), Molecular actions of ebselen – an anti-inflammatory antioxidant; Gen. Pharmacol., 26 1153 2) Parnham et al. (2000), Ebselen: prospective therapy for cerebral ischaemia; Expert. Opin. Investig. Drugs, 9 607 3) Masumoto et al. (1996), Kinetic study of the reaction of ebselen with peroxynitite; FEBS Lett., 398 179 4) Nakamura et al. (2002), Ebselen, a glutathione peroxidase mimetic seleno-organic compound, as a multifunctional antioxidant. Implication for inflammation-associated carcinogenesis; J. Biol. Chem., 277 2687

InChI:InChI=1/C13H9NOSe/c15-13-11-8-4-5-9-12(11)16-14(13)10-6-2-1-3-7-10/h1-9H

Upstream product

• 1441-85-6 2-(chloroseleno)benzoyl chloride 
• 62-53-3 aniline 
• 60975-10-2 3-chloro-2-phenyl-benzo[d]isoselenazolium; chloride 
• 93-98-1 N-phenyl benzoyl amide 
• 60940-33-2 2-benzylbenzo[d][1,2]selenazol-3(2H)-one 
• 114744-69-3 S-(2-phenyl carbamoyl benzeneselenenyl)benzylmercaptan 
• 110-05-4 di-tert-butyl peroxide 
• 106663-84-7 2,2‘-diselenobis(N-phenylbenzamide) 
• 104473-83-8 2-phenyl-1,2-benzioselenazol-3(2H)-one selenoxide 
• 10282-57-2 2-bromobenzanilide 
• 6512-83-0 2,2'-diselanediyl-di-benzoic acid 
• 118-92-3 anthranilic acid 
• 356761-43-8 ebselen seleninic acid 
• 6833-13-2 2-chlorobenzanilide 

Downstream Products

• 60975-10-2 3-chloro-2-phenyl-benzo[d]isoselenazolium; chloride 
• 101562-89-4 S-(2-phenyl carbamoyl benzeneselenenyl)-glutathione 
• 118398-39-3 C₂₀H₂₅NOSSe 
• 118398-44-0 C₁₉H₂₀N₂O₄SSe 
• 150-60-7 dibenzyl disulphide 
• 106663-84-7 2,2‘-diselenobis(N-phenylbenzamide) 
• 114744-69-3 S-(2-phenyl carbamoyl benzeneselenenyl)benzylmercaptan 
• 104030-64-0 C₁₅H₁₅NOSSe 
• 60940-24-1 2-methylseleno-N-phenylbenzamide 
• 104473-83-8 2-phenyl-1,2-benzioselenazol-3(2H)-one selenoxide 
• 108085-74-1 dibenzo<1,4>selenazepin-11(10H)-one 
• 60940-41-2 benzo[d]isoselenazol-3-yl-phenyl-amine 
• 101563-03-5 S-(2-phenylcarbamoyl-phenylselenyl)-L-cysteinethylester 
• 101563-07-9 S-(2-phenylcarbamoyl phenylselenyl)-DL-homocysteine 

Relevant articles and documents

Thermal and Photoinduced Copper-Promoted C-Se Bond Formation: Synthesis of 2-Alkyl-1,2-benzisoselenazol-3(2H)-ones and Evaluation against Mycobacterium tuberculosis

2-Alkyl-1,2-benzisoselenazol-3(2H)-ones, represented by ebselen (1a), are being studied intensively for a range of medicinal applications. We describe both a new thermal and photoinduced copper-mediated cross-coupling between potassium selenocyanate (KSeCN) and N-substituted ortho-halobenzamides to form 2-alkyl-1,2-benzisoselenazol-3(2H)-ones containing a C-Se-N bond. The copper ligand (1,10-phenanthroline) facilitates C-Se bond formation during heating via a mechanism that likely involves atom transfer (AT), whereas, in the absence of ligand, photoinduced activation likely proceeds through a single electron transfer (SET) mechanism. A library of 15 2-alkyl-1,2-benzisoselenazol-3(2H)-ones was prepared. One member of the library was azide-containing derivative 1j that was competent to undergo a strain-promoted azide-alkyne cycloaddition. The library was evaluated for inhibition of Mycobacterium tuberculosis (Mtb) growth and Mtb Antigen 85C (Mtb Ag85C) activity. Compound 1f was most potent with a minimal inhibitory concentration (MIC) of 12.5 μg/mL and an Mtb Ag85C apparent IC50 of 8.8 μM.

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.