273404-37-8 Usage
Description
(S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide is a complex organic compound with potential applications in various fields due to its unique chemical structure and properties.
Uses
1. Used in Pharmaceutical Applications:
(S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide is used as a prodrug for the caspase-1/4-selective inhibitor VRT-43198. It is effective in inhibiting LPS-induced IL-1β production in primary human PBMC cultures and has shown in vivo anti-inflammatory efficacy against various inflammatory conditions.
2. Used in Anti-Convulsant Applications:
In the field of neurology, this compound demonstrates anti-convulsant activity by inhibiting the biosynthesis of interleukin-1β, which is involved in the pathogenesis of seizures and epilepsy.
3. Used in Anti-Inflammatory Applications:
(S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide is used to suppress the severity of inflammatory responses, such as those induced by LPS, oxazolone, and collagen, which are relevant to conditions like delayed-type hypersensitivity, arthritis, and atherosclerosis.
4. Used in Neuroprotection:
(S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide provides neuroprotection in models of temporal lobe epilepsy, stroke, and Alzheimer's disease, suggesting its potential use in the treatment and prevention of neurodegenerative conditions.
5. Used in the Prevention of Glia Pyroptosis:
In the context of multiple sclerosis, this compound inhibits glial pyroptosis, which is a form of programmed cell death that contributes to the pathology of the disease.
6. Used in the Treatment of Atherosclerotic Disease:
By inhibiting pyroptosis in vascular smooth muscle cells during atherogenesis, this compound may offer a therapeutic approach to treating atherosclerotic disease.
7. Used in the Modulation of Depressive-Like Behaviors:
It has been shown to inhibit the activation and expression of the NLRP3 inflammasome, which is associated with depressive-like behaviors induced by chronic mild stress.
Please note that the specific applications and industries for (S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide are hypothetical and based on the provided data. Further research and clinical trials would be necessary to confirm these uses and establish the compound's efficacy and safety in each application.
Biochem/physiol Actions
Cell permeable: yes
References
Wannamaker et al. (2007)(S)-1-((S)-2-{[1-(4-Amino-3-chlorophenyl)-methanoyl]-amino}-3,3-dimethylbutanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)-amide (VX-765), an Orally Available Selective Interleukin (IL)-Converting Enzyme/Caspase-1 Inhibitor, Exhibits Potent Anti-Inflammatory Activities by Inhibiting the Release of IL-1b and IL-18, J. Pharmacol. Exp. Ther.?321 509
Zhang et al. (2015) NLRP3 Inflammasome Mediates Chronic Mild Stress-Induced Depression in Mice via Neuroinflammation, J. Neuropsychopharmacol. 18 pyv006
McKenzie et al. (2018) Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis, Proc. Natl. Acad. Sci USA 115 E6065
Li et al. (2020) VX-765 attenuates atherosclerosis in ApoE deficient mice by modulating VSMCs pyroptosis, Exp. Cell Res. 389 111847
Maroso et al. (2011) Interleukin-1b biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice, Neurotherapeutics 8 304
Noe et al. (2013) Pharmacological blockade of IL-1b/IL-1 receptor type 1 axis during epileptogenesis provides neuroprotection in two rat models of temporal lobe epilepsy, Neurobiol. Dis. 59 183
Li et al. (2019) Caspase-1 inhibition mediates neuroprotection in experimental stroke by polarizing M2 microglia/macrophage and suppressing NF-kB activation, Biochem. Biophys. Res. Commun. 513 479
Flores et al. (2018) Caspase-1 inhibition alleviates cognitive impairment in an Alzheimer’s disease mouse model, Nat. Commun. 9 3916
Check Digit Verification of cas no
The CAS Registry Mumber 273404-37-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,7,3,4,0 and 4 respectively; the second part has 2 digits, 3 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 273404-37:
(8*2)+(7*7)+(6*3)+(5*4)+(4*0)+(3*4)+(2*3)+(1*7)=128
128 % 10 = 8
So 273404-37-8 is a valid CAS Registry Number.
273404-37-8Relevant articles and documents
Prodrug of an ice inhibitor
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, (2016/11/24)
This invention describes an ICE inhibitor prodrug (I) having good bioavailability. Compound I is useful for treating IL-1 mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, inflammatory periton
A highly potent and selective caspase 1 inhibitor that utilizes a key 3-cyanopropanoic acid moiety
Boxer, Matthew B.,Quinn, Amy M.,Shen, Min,Jadhav, Ajit,Leister, William,Simeonov, Anton,Auld, Douglas S.,Thomas, Craig J.
scheme or table, p. 730 - 738 (2011/02/21)
Herein, we examine the potential of a nitrile-containing propionic acid moiety as an electrophile for covalent attack by the active-site cysteine residue of caspase 1. The syntheses of several cyanopropanate-containing small molecules based on the optimiz
PROCESSES AND INTERMEDIATES
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Page/Page column 77-78, (2008/06/13)
The invention relates to processes and compounds useful for producing modified aspartic acid derivatives, such as aspartic acid aldehyde moieties. Aspartic acid derivatives are useful for preparing caspase inhibitors and/or prodrugs thereof.
