Belnacasan

Base Information

• Chemical Name: Belnacasan
• CAS No.: 273404-37-8
• Molecular Formula: C₂₄H₃₃ClN₄O₆
• Molecular Weight: 509.002
• European Community (EC) Number: 695-154-4
• UNII: 00OLE78529
• ChEMBL ID: CHEMBL2107819
• DSSTox Substance ID: DTXSID901017651
• NCI Thesaurus Code: C171755
• Nikkaji Number: J2.556.000K
• Wikidata: Q27075000
• Wikipedia: Belnacasan
• Mol file: 273404-37-8.mol

Synonyms:(S)-1-((S)-2-1((-(4-amino-3-chloro-phenyl)-methanoyl)-amino)-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide;(S)-3-((1-((S)-1-((S)-2-((1-(4-amino-3-chlorophenyl)methanoyl)amino)-3,3-dimethyl-butanoyl)pyrrolidin-2yl)methanoyl)amino)-4-oxo-butyric acid;1-((2S)-2-((4-amino-3-chlorobenzoyl)amino)-3,3-dimethylbutanoyl)-N-((2R,3S)-2- ethoxy-5-oxo-tetrahydrofuran-3-yl)-l-prolinamide;belnacasan;L-prolinamide, N-(4-amino-3-chlorobenzoyl)-3-methyl-L-valyl-N-((1S)-2-carboxy-1-formylethyl)-;N-(4-amino-3-chlorobenzoyl)-3-methyl-L-valyl-N-((1S)-2-carboxy-1-formylethyl)-L-prolinamide;O-desethyl-belnacasan;VRT 043198;VRT-043198;VX 765;VX-765;VX-765 hemiketal;VX765

Chemical Property of Belnacasan

Chemical Property:

• Boiling Point: 779.0±60.0 °C(Predicted)
• PKA: 12.60±0.40(Predicted)
• PSA: 147.04000
• Density: 1.32
• LogP: 3.78620
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (>25 mg/ml)
• XLogP3: 2.3
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 8
• Exact Mass: 508.2088625
• Heavy Atom Count: 35
• Complexity: 818

Purity/Quality:

98% ^*data from raw suppliers

VX-765 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCOC1C(CC(=O)O1)NC(=O)C2CCCN2C(=O)C(C(C)(C)C)NC(=O)C3=CC(=C(C=C3)N)Cl
• Isomeric SMILES: CCO[C@H]1[C@H](CC(=O)O1)NC(=O)[C@@H]2CCCN2C(=O)[C@H](C(C)(C)C)NC(=O)C3=CC(=C(C=C3)N)Cl
• Recent ClinicalTrials: Safety, Tolerability, and Treatment Effect of Belnacasan in Patients With COVID-19
• Recent EU Clinical Trials: A Phase 2b, Randomized, Double Blind, Placebo Controlled, Parallel Group, Dose Ranging Study to Evaluate the Efficacy and Safety of VX-765 in Subjects With Treatment Resistant Partial Epilepsy With a 24-Week Open-Label Extension
• Description: Belnacasan (273404-37-8) is a prodrug of VRT-043198, a potent (Ki = 0.8 nM ICE/caspase-1; <0.6nM caspase-4) and selective inhibitor of interleukin-converting enzyme/caspase-1 subfamily caspases.1 VRT-043198 ICE/caspase-1 IC50 = 0.67 μM PBMCs, 1.0 μM whole blood.? It inhibited the release of IL-1b and IL-18 from human monocytes in vitro and their production in vivo in models of inflammation. Belnacasan inhibited the activation and expression of the NLRP3 Inflammasome leading to moderation of depressive-like behaviors induced by chronic mild stress2 and prevention of glial pyroptosis in multiple sclerosis models3. It inhibited pyroptosis in vascular smooth muscle cells during atherogenesis suggesting a possible therapeutic effect in treating atherosclerotic disease.4 Belnacasan reduced acute seizures and drug resistant chronic epileptic activity in mice5 and provided neuroprotection in two rat models of temporal lobe epilepsy6.? It also displays protective effects in models of stroke7and Alzheimer’s disease8.
• Uses: VX-765 shows anti-convulsant activity by inhibiting interlukin-1β biosynthesis.

Technology Process of Belnacasan

There total 16 articles about Belnacasan which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 77.0%

CH2Cl2/MeOH + 1-[2-(4-amino-3-chloro-benzoylamino)-3,3-dimethyl-butyryl]-pyrrolidine-2-carboxylic acid + 1,3-dimethylbarbituric acid (DMBA) + diisopropylethylamine (DIPEA) → 1-[2-(4-amino-3-chloro-benzoylamino)-3,3-dimethyl-butyryl]-pyrrolidine-2-carboxylic acid (2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (851091-96-8,273404-37-8)

Guidance literature:

With 1,2-dichloro-ethane; Pd(PPh₃)4; In dichloromethane; N,N-dimethyl-formamide;

Reference yield: 72.0%

3-amino-4-oxo-butanoic acid β-tert-butyl ester diethyl acetal (409369-63-7) + (S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)pyrrolidine-2-carboxylic acid (374773-70-3) → VX-765 (851091-96-8,273404-37-8)

Guidance literature:

3-amino-4-oxo-butanoic acid β-tert-butyl ester diethyl acetal; With N,N-dimethyl-formamide; for 0.0833333h;

(S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)pyrrolidine-2-carboxylic acid; With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 0 ℃; for 1h;

With trifluoroacetic acid; In dichloromethane; for 1h;

DOI:10.1002/cmdc.200900531

Reference yield: 72.0%

3-amino-4-oxo-butanoic acid β-tert-butyl ester diethyl acetal (409369-63-7) + (S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)pyrrolidine-2-carboxylic acid (374773-70-3) → C24H33ClN4O6 (851091-96-8,273404-37-8)

Guidance literature:

3-amino-4-oxo-butanoic acid β-tert-butyl ester diethyl acetal; In N,N-dimethyl-formamide; for 0.0833333h;

(S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)pyrrolidine-2-carboxylic acid; With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 0 ℃; for 1h;

With trifluoroacetic acid; In dichloromethane; for 1h;

upstream raw materials:

C₁₇H₂₉N₃O₅

4-amino-3-chlorobenzoic acid

(S)-N-carbobenzoxy-tert-butylleucine

1-[2-(4-amino-3-chlorobenzoylamino)-3,3-dimethylbutyryl]pyrrolidine-2-carboxylic acid tert-butyl ester

Refernces

• 1、 -. "Caspase inhibitors". . . Retrieved 2016/12/16.
• 2、 Tanoury, Gerald J.,Chen, Minzhang,Dong, Yong,Forslund, Raymond E.,Magdziak, Derek. "Development of a novel Pd-catalyzed N-acyl vinylogous carbamate synthesis for the key intermediate of ICE inhibitor VX-765". . p. 185 - 188. Retrieved 2008/09/18.