89886-73-7

Basic information

• Product Name: 2,3-Oxiranedicarboxylicacid,monoethylester,(2S,3S)-(9CI)
• Synonyms: 2,3-Oxiranedicarboxylicacid,monoethylester,(2S,3S)-(9CI);(2S,3S)-3-(ethoxycarbonyl)oxirane-2-carboxylic acid;(2S,3S)-2,3-Oxiranedicarboxylic Acid Monoethyl Ester;(2S,3S)-3-(Ethoxycarbonyl)oxirane-2-carboxylic acid 95%
• CAS NO: 89886-73-7
• Molecular Formula: C₆H₈O₅
• Molecular Weight: 160.13
• Product Categories: CARBOXYLICESTER;CARBOXYLICACID
• Mol File: 89886-73-7.mol

Chemical Properties

• Boiling Point: 278.9±40.0 oC (760 Torr)
• Flash Point: 118.5±20.8 oC
• Appearance: /
• Density: 1.447±0.06 g/cm3 (20 oC 760 Torr)
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 3.14±0.40(Predicted)
• CAS DataBase Reference: 2,3-Oxiranedicarboxylicacid,monoethylester,(2S,3S)-(9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: 2,3-Oxiranedicarboxylicacid,monoethylester,(2S,3S)-(9CI)(89886-73-7)
• EPA Substance Registry System: 2,3-Oxiranedicarboxylicacid,monoethylester,(2S,3S)-(9CI)(89886-73-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26
• Hazardous Substances Data: 89886-73-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2,3-Oxiranedicarboxylicacid,monoethylester,(2S,3S)-(9CI) is used as a key intermediate in the synthesis of aza-peptidyl inhibitors of lysosomal asparaginyl endopeptidase, legumain. These inhibitors are important for the development of drugs targeting various diseases, including cancer and neurodegenerative disorders, by modulating the activity of legumain.
Used in Cancer Research:
In the field of cancer research, 2,3-Oxiranedicarboxylicacid,monoethylester,(2S,3S)-(9CI) is used as a building block in the synthesis of irreversible epidermal growth factor receptor (EGFR) inhibitors. These inhibitors can effectively target and inhibit the activity of EGFR, a receptor tyrosine kinase involved in cell growth and proliferation, which is often overexpressed in various types of cancer.
Used in Biochemical Research:
2,3-Oxiranedicarboxylicacid,monoethylester,(2S,3S)-(9CI) is also used in the synthesis of probes for cathepsins, a family of protease enzymes that play a crucial role in various biological processes, including antigen presentation, apoptosis, and tissue remodeling. The development of selective and potent cathepsin inhibitors can help in understanding the role of these enzymes in disease progression and may lead to the discovery of new therapeutic agents for various conditions.

Upstream product

• 3291-46-1 (2SR,3SR)-oxirane-2,3-dicarboxylic acid diethyl ester 
• 80640-15-9 diethyl (2S,3R)-(+)-erythro-2-hydroxy-3-bromosuccinate 
• 13811-71-7 diethyl (2S,3S)-tartrate 
• 57968-71-5 (+/-)-diethyl tartrate 
• 3291-46-1 (2S,3S)-diethyl oxirane-2,3-dicarboxylate 

Downstream Products

• 100464-19-5 2-ethyl 3-(4-nitrophenyl) (2S,3S)-oxirane-2,3-dicarboxylate 
• 154415-60-8 L-trans-epoxysuccinyl-L-tyrosylamido(3-methyl)butane ethylester 
• 154415-61-9 L-trans-epoxysuccinyl-3-iodo-L-tyrosylamido(3-methyl)butane ethylester 
• 154415-62-0 L-trans-epoxysuccinyl-3,5-diiodo-L-tyrosylamido(3-methyl)butane ethylester 
• 75657-73-7 N-((2S,3S)-3-trans-ethoxycarbonyloxiran-2-carbonyl)-L-leucine benzyl ester 
• 159086-41-6 N-((2S,3S)-3-trans-ethoxycarbonyloxiran-2-carbonyl)-L-phenylalanine benzyl amide 
• 128301-63-3 N-((2S,3S)-3-trans-ethoxycarbonyloxiran-2-carbonyl)-L-isoleucine benzyl ester 
• 245660-09-7 {2S-[2α,3β(S)]}-Oxirane carboxylic acid 3-[({3-Phenyl-1-[(benzyloxy)carbonyl]propyl}amino)carbonyl] ethyl ester 
• 500228-05-7 (+)-(2S,3S)-3-{{(1S)-1-{{4-{[(Benzyloxy)carbonyl]amino}butyl}{3-{[(benzyloxy)carbonyl]amino}propyl}carbamoyl}-2'-[4-(benzyloxy)phenyl]ethyl}carbamoyl}oxiran-2-carbonsaeure-ethylester 
• 192815-59-1 Ethyl L-3-trans-(2-phenylethylcarbamoyl)oxirane-2-carboxylate 
• 192815-63-7 Ethyl L-3-trans-benzylcarbamoyloxirane-2-carboxylate 
• 1584149-71-2 C₃₀H₄₃N₇O₁₀ 
• 245660-28-0 {2S-[2α,3β(S)]}-3-{[(3-Phenyl-1-{[(5-t-butyldimethylsilanoxylpentyl)amino]carbonyl}propyl)amino]carbonyl}oxirane carboxylic acid ethyl ester 

Relevant articles and documents

2,3-EPOXY SUCCINYL DERIVATIVE, PREPARATION METHOD THEREFOR, AND USES THEREOF

The present invention relates to a 2,3-epoxy succinyl derivative, a preparation method and a use thereof, in particular, the present invention relates to a compound represented by Formula (1), a racemate or an optical isomer thereof, a solvate thereof, or

Design, synthesis, and structure–activity relationship study of epoxysuccinyl–peptide derivatives as cathepsin B inhibitors

Cathepsin B is a lysosomal cysteine protease involved in many diseases. The present research demonstrates that derivatives of epoxysuccinyl–peptide are effective and selective cathepsin B inhibitors. We synthesized a series of epoxysuccinyl–peptide deriva

Cysteine protease inhibitors and uses thereof

The invention provides for novel cysteine protease inhibitors and compositions comprising novel cysteine protease derivatives. The invention further provides for methods for treatment of neurodegenerative diseases comprising administration novel cysteine

Design, synthesis, and optimization of novel epoxide incorporating peptidomimetics as selective calpain inhibitors

Hyperactivation of the calcium-dependent cysteine protease calpain 1 (Cal1) is implicated as a primary or secondary pathological event in a wide range of illnesses and in neurodegenerative states, including Alzheimer's disease (AD). E-64 is an epoxide-containing natural product identified as a potent nonselective, calpain inhibitor, with demonstrated efficacy in animal models of AD. By use of E-64 as a lead, three successive generations of calpain inhibitors were developed using computationally assisted design to increase selectivity for Cal1. First generation analogues were potent inhibitors, effecting covalent modification of recombinant Cal1 catalytic domain (Cal1cat), demonstrated using LC-MS/MS. Refinement yielded second generation inhibitors with improved selectivity. Further library expansion and ligand refinement gave three Cal1 inhibitors, one of which was designed as an activity-based protein profiling probe. These were determined to be irreversible and selective inhibitors by kinetics studies comparing full length Cal1 with the general cysteine protease papain.

Design, synthesis, and screen of cathepsin K inhibitors

We synthesized a series of epoxysuccinic acid derivatives and evaluated their in vitro cathepsin K inhibitory activity The screening results show that the potency of compounds 9e, 9d, 9p, 9j and 9k (IC50 ≤ 0.005 μmol/L) were equal to or greater than that of the lead compound 9a. Less hydrophobic compounds showed weaker potency, which can be explained by the hydrophobic nature of the cathepsin K binding pockets.

Two-step labeling of endogenous enzymatic activities by Diels-Alder ligation

A ligation strategy based on the Diels-Alder [4+2] cycloaddition for the two-step activity-based labeling of endogenously expressed enzymes in complex biological samples has been developed. A panel of four diene-derivatized proteasome probes was synthesized, along with a dienophile-functionalized BODIPY(TMR) tag. These probes were applied in a Diels-Alder labeling procedure that enabled us to label active proteasome β-subunits selectively in cellular extracts and in living cells. We were also able to label the activity of cysteine proteases in cell extracts by utilizing a diene-derivatized cathepsin probe. Importantly, the Diels-Alder strategy described here is fully orthogonal with respect to the Staudinger-Bertozzi ligation, as demonstrated by the independent labeling of different proteolytic activities by the two methods in a single experiment.

Novel irreversible epidermal growth factor receptor inhibitors by chemical modulation of the cysteine-trap portion

Irreversible EGFR inhibitors can circumvent acquired resistance to first-generation reversible, ATPcompetitive inhibitors in the treatment of non-small-cell lung cancer. They contain both a driver group, which assures target recognition, and a warhead, generally an acrylamide or propargylamide fragment that binds covalently to Cys797 within the kinase domain of EGFR. We performed a systematic exploration of the role for the warhead group, introducing different cysteine-trapping fragments at position 6 of a traditional 4-anilinoquinazoline scaffold. We found that different reactive groups, including epoxyamides (compounds 3-6) and phenoxyacetamides (compounds 7-9), were able to irreversibly inhibit EGFR. In particular, at significant lower concentrations than gefitinib (1), (2R,3R)N-(4-(3-bromoanilino)quinazolin-6-yl)- 3 -(piperidin-1 -ylmethyl)oxirane-2-carboxamide (6) inhibited EGFR autophosphorylation and downstream signaling pathways, suppressed proliferation, and induced apoptosis in gefitinib-resistant NSCLC H1975 cells, harboring the T790M mutation in EGFR.

Aza-peptidyl michael acceptor and epoxide inhibitors - Potent and selective inhibitors of Schistosoma mansoni and Ixodes ricinus legumains (asparaginyl endopeptidases)

Aza-peptide Michael acceptors and epoxides with the general structure of YCO-Ala-Ala-AAsn-trans-CH=CHCOR and YCO-Ala-Ala-AAsn-EP-COR, respectively, are shown to be potent inhibitors of asparaginyl endopeptidases (legumains) from the bloodfluke, Schistosoma mansoni (SmAE), and the hard tick, Ixodes ricinus (IrAE). Structure-activity relationships (SARs) were determined for a set of 41 aza-peptide Michael acceptors and eight aza-peptide epoxides. Both enzymes prefer disubstituted amides to monosubstituted amides in the P10 position, and potency increased as we increased the hydrophobicity of the inhibitor in this position. Extending the inhibitor to P5 resulted in increased potency, especially against IrAE, and both enzymes prefer small over large hydrophobic residues at P2. Aza-peptide Michael acceptor inhibitors are more potent than aza-peptide epoxide inhibitors, and for some of these compounds, second-order inhibiton rate constants are the fastest yet discovered. Given the central functions of these enzymes in both parasites, the data presented here may facilitate the eventual design of selective antiparasitic drugs.

NOVEL DRUGS FOR DEMENTIA

The invention is directed to compounds that are prodrugs containing a chemical delivery system (CDS) moiety and a cysteine protease inhibitor moiety. The CDS moiety targets the prodrug to the brain or central nervous system. The cysteine protease inhibitor inhibits cysteine proteases upon release from the prodrug. Cysteine protease inhibitors are effective for treating dementia, Alzheimer's disease and vascular dementia. Targeting the brain or central nervous system offers significant advantages in treating these conditions and diseases. A preferred CDS prodrug is a dihydrotrigoneline CDS moiety coupled to an epoxysuccinyl peptide cysteine protease inhibitor moiety.

An improved preparation of the activity-based probe JPM-OEt and in situ applications

A short, stereoselective synthesis of the general, cell permeable cathepsin probe JPM-OEt, is presented. The synthetic route is improved and described in more detail than previous reports for related compounds. This serves as a facile method for the synth