Boceprevir

Base Information

• Chemical Name: Boceprevir
• CAS No.: 394730-60-0
• Molecular Formula: C27H45N5O5
• Molecular Weight: 519.685
• Hs Code.: 2933599590
• European Community (EC) Number: 800-043-2
• UNII: 89BT58KELH
• DSSTox Substance ID: DTXSID30960103
• Wikipedia: Boceprevir
• Wikidata: Q410551
• NCI Thesaurus Code: C117292
• Pharos Ligand ID: FC2DSF1KRQ5F
• Metabolomics Workbench ID: 65128
• ChEMBL ID: CHEMBL218394
• Mol file: 394730-60-0.mol

Synonyms:boceprevir;N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide;Sch 503034;Sch-503034;Sch503034;victrelis

Chemical Property of Boceprevir

Chemical Property:

• Appearance/Colour: white powder
• PKA: 12.82±0.40(Predicted)
• PSA: 150.70000
• Density: 1.162 g/cm³
• LogP: 3.52210
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (up to 15 mg/ml with warming)
• XLogP3: 3.1
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 10
• Exact Mass: 519.34206955
• Heavy Atom Count: 37
• Complexity: 959

Purity/Quality:

99% ^*data from raw suppliers

Boceprevir ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Hepatitis C Agents
• Canonical SMILES: CC1(C2C1C(N(C2)C(=O)C(C(C)(C)C)NC(=O)NC(C)(C)C)C(=O)NC(CC3CCC3)C(=O)C(=O)N)C
• Isomeric SMILES: CC1([C@@H]2[C@H]1[C@H](N(C2)C(=O)[C@H](C(C)(C)C)NC(=O)NC(C)(C)C)C(=O)NC(CC3CCC3)C(=O)C(=O)N)C
• Recent ClinicalTrials: Efficacy and Safety of Therapy Against HCV Based on Direct-acting Antivirals in Real-life Conditions
• Recent EU Clinical Trials: Response-guided triple therapy using boceprevir in combination with PEGIFN/RBV in HIV/HCV coinfected patients
• Description: In May 2011, the U.S. FDA approved boceprevir (SCH-503034), to be given in combination with peginterferon alfa plus ribavirin, for the treatment of patients with chronic hepatitis C genotype 1 viral infection. Boceprevir and telaprevir are the first hepatitis C virus (HCV) protease inhibitors to be approved for the treatment of HCV infection. Boceprevir is an inhibitor of HCV NS3-4A protease, an essential enzyme required by HCV for posttranslational processing of viral proteins into their mature forms. Boceprevir binds covalently, but reversibly, to the active site serine by addition of the hydroxyl group to the keto-amide functionality. Boceprevir inhibits HCV NS3-4A protease with a Ki of 14 nM. In cell culture, the EC50 of boceprevir was 200 nM for an HCV replicon constructed from genotype 1b. Boceprevir was two-to threefold less potent against HCV replicon from genotypes 1a, 2, and 3. The potency of boceprevir decreased threefold in the presence of human serum. Boceprevir was discovered through a series of systematic truncations and modifications of a keto-amide undecapeptide lead molecule. Boceprevir is synthesized by coupling of 3-amino-4- cyclobutyl-2-hydroxybutyramide or the related oxobutyramide with a cyclopropyl-pyrrolidine carboxylic acid intermediate. The pyrrolidine derivative can be prepared via cyclopropanation of a bicyclic lactam derivative or by conversion of 3,3-dimethylcyclopropane-1,2-dicarboxylic acid to the pyrrolidine in a multistep route. Boceprevir is a 1:1 mixture of diastereomers at the readily epimerizable position a to the keto group. Boceprevir is an inhibitor of hepatitis C virus (HCV) non-structural protease 3/4A (NS3/4A; Ki = 14 nM for the HCV genotype 1b enzyme). Boceprevir inhibits HCV replication in Huh7 cells (EC50 = 200 nM). It also inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro; Ki = 1.8 μM) and reduces cytopathic effects of SARS-CoV-2 in Vero cells (EC50 = 1.31 μM). Formulations containing boceprevir have been used in the treatment of HCV.
• Uses: An NS3 serine protease inhibitor of hepatitis C virus, for the treatment of HCV infection. It is a COVID19-related research product.
• Clinical Use: Boceprevir is an oral inhibitor of HCV NS3/4A protease for the treatment of the chronic hepatitis C genotype infection. It is approved as combination therapy with Peg-IFN-alpha and ribavarin to treat adult patients with compensated liver diseasewhoare either treatment naive or who have experienced prior failed therapy with interferon and ribavarin. Boceprevir was initially discovered by Schering-Plough and developed and marketed by Merck & Co. since its acquisition of Schering-Plough in 2009. Several publications have highlighted the discovery of this drug, which evolved from a potent initial undecapeptide lead structure to boceprevir (VII) as a drug candidate with potent activity and desirable PK properties.
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration possibly reduced by rifampicin - avoid. Anticoagulants: avoid with apixaban. Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin, phenobarbital, phenytoin and primidone - avoid. Antifungals: concentration increased by ketoconazole. Antimalarials: avoid with artemether and lumefantrine. Antipsychotics: avoid pimozide; possibly increases lurasidone and quetiapine concentration - avoid. Antivirals: reduces concentration of atazanavir; avoid with daclatasvir, darunavir, fosamprenavir and lopinavir; concentration of both drugs reduced with ritonavir. Anxiolytics and hypnotics: increased oral midazolam concentration - avoid. Ciclosporin: concentration of ciclosporin increased. Cilostazol: possibly increases cilostazol concentration. Cytotoxics: possibly increases bosutinib concentration - avoid or reduce bosutinib dose; avoid with dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, olaparib, pazopanib, sorafenib and sunitinib; reduce dose of ruxolitinib. Domperidone: possible increased risk of ventricular arrhythmias - avoid. Ergot alkaloids: avoid concomitant use. Guanfacine: concentration possibly increased, halve guanfacine dose. Lipid-regulating drugs: enhances effects and toxicity of atorvastatin, reduce atorvastatin dose; increases pravastatin concentration; avoid with simvastatin. Oestrogens: possibly causes contraception failure. Sirolimus: possibly increases sirolimus concentration. Tacrolimus: concentration of tacrolimus increased, reduce tacrolimus dose.

Technology Process of Boceprevir

There total 50 articles about Boceprevir 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: 94.0%

(1R,2S,5S)-N-(4-amino-1-cyclobutyl-3-hydroxy-4-oxobutan-2-yl)-3-((S)-2-(3-(tert-butyl)ureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicylo[3.1.0]-hexane-2-carboxamide (394735-28-5) → boceprevir (394730-60-0)

Guidance literature:

(1R,2S,5S)-N-(4-amino-1-cyclobutyl-3-hydroxy-4-oxobutan-2-yl)-3-((S)-2-(3-(tert-butyl)ureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicylo[3.1.0]-hexane-2-carboxamide; With sodium hypochlorite solution; sodium acetate; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; In tert-butyl methyl ether; at 10 - 20 ℃;

With water; acetic acid; In tert-butyl methyl ether; for 2.25h;

With sodium hypochlorite solution; ascorbic acid; more than 3 stages; Product distribution / selectivity;

Reference yield: 94.0%

C27H46N5O8S(1-)*Na(1+) (817170-37-9) → boceprevir (394730-60-0)

Guidance literature:

With Oxone; In tert-butyl methyl ether; water; at 25 ℃; for 1h; Purification / work up;

Reference yield: 90.0%

(1R,2S,5S)-3-((S)-2-(3-tert-butylureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylic acid (816444-90-3) + C8H14N2O2*ClH (817169-86-1) → boceprevir (394730-60-0) + N-methylmorpholine hydrochloride (3651-67-0)

Guidance literature:

With 4-methyl-morpholine; isobutyl chloroformate; In ethyl acetate; at 0 - 10 ℃; for 1h;

upstream raw materials:

(1R,2S,5S)-N-(4-amino-1-cyclobutyl-3-hydroxy-4-oxobutan-2-yl)-3-((S)-2-(3-(tert-butyl)ureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicylo[3.1.0]-hexane-2-carboxamide

(2-cyclobutyl-1-formylethyl)carbamic acid tert-butyl ester

(2-cyano-1-cyclobutylmethyl-2-hydroxyethyl)carbamic acid tert-butyl ester

2-(tert-butoxycarbonylamino)-3-cyclobutylpropanoic acid

Refernces

• 1、 -. "PROCESS FOR PREPARATION OF BOCEPREVIR AND INTERMEDIATES THEREOF". Page/Page column 15; 33-34; 41. . Retrieved 2014/05/07.
• 2、 -. "BISULFITE PURIFICATION OF AN ALPHA-KETO AMIDE". Page/Page column 20; 21; 24. . Retrieved 2008/12/06.