394735-22-9

Usage

Uses

Used in Pharmaceutical Industry:
(2-Carbamoyl-1-cyclobutylmethyl-2-hydroxy-ethyl)-carbamic acid tert-butyl ester is used as a key intermediate compound for the synthesis of hepatitis C virus (HCV) NS3 serine protease inhibitors. Its unique structure allows it to interact with the active site of the NS3 protease, thereby inhibiting its function and helping to combat the virus.
Used in Drug Development:
In the field of drug development, (2-Carbamoyl-1-cyclobutylmethyl-2-hydroxy-ethyl)-carbamic acid tert-butyl ester serves as a valuable building block for designing and synthesizing novel therapeutic agents. Its chemical properties and reactivity make it a promising candidate for further modification and optimization to enhance its potency, selectivity, and pharmacokinetic properties.
Used in Medicinal Chemistry Research:
(2-Carbamoyl-1-cyclobutylmethyl-2-hydroxy-ethyl)-carbamic acid tert-butyl ester is also utilized in medicinal chemistry research to explore its potential as a lead compound for the development of new drugs targeting various diseases. Its structural features can be exploited to design molecules with improved biological activity and reduced side effects.

InChI:InChI=1/C13H24N2O4/c1-13(2,3)19-12(18)15-9(10(16)11(14)17)7-8-5-4-6-8/h8-10,16H,4-7H2,1-3H3,(H2,14,17)(H,15,18)

Upstream product

• 394735-20-7 (2-cyano-1-cyclobutylmethyl-2-hydroxyethyl)carbamic acid tert-butyl ester 
• 864765-28-6 3-(tert-butoxycarbonylamino)-4-cyclobutyl-2-hydroxybutanoic acid 
• 1433545-53-9 ethyl 2-chloro-4-cyclobutyl-3-oxobutanoate 
• 1433545-62-0 4-cyclobutyl-1-ethoxy-1,3-dioxobutan-2-yl 4-methoxybenzoate 
• 1433545-74-4 (2E)-3-amino-4-cyclobutyl-1-ethoxy-1-oxobut-2-en-2-yl 4-methoxybenzoate 
• 1433545-85-7 3-[(tert-butoxycarbonyl)amino]-4-cyclobutyl-1-ethoxy-1-oxobut-2-yl 4-methoxybenzoate 
• 4426-03-3 cyclobutyl acetonitrile 
• 63659-30-3 cyclobutylmethyl methanesulfonate 
• 4415-82-1 cyclobutanemethanol 
• 885280-12-6 ethyl 4-cyclobutyl-3-oxobutanoate 
• 1036931-37-9 3-amino-4-cyclobutyl-2-hydroxybutanoic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 17247-58-4 (Bromomethyl)cyclobutane 
• 1025799-39-6 2-(benzhydrylidene-amino)-3-cyclobutyl-propionic acid ethyl ester 

Downstream Products

• 1036931-36-8 3-amino-4-cyclobutyl-2-hydroxybutanamide hydrochloride 
• 394735-25-2 {(S)-2-[(1R,2S,5S)-2-(2-Carbamoyl-1-cyclobutylmethyl-2-hydroxy-ethylcarbamoyl)-6,6-dimethyl-3-aza-bicyclo[3.1.0]hex-3-yl]-1-cyclohexyl-2-oxo-ethyl}-carbamic acid tert-butyl ester 
• 394735-28-5 (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 
• 394730-60-0 boceprevir 

Relevant academic research and scientific papers

A New and convenient synthesis of the boceprevir P1 fragment, β-aminoα-hydroxy amide

A new and convenient synthesis of the P1 fragment of HCV inhibitor, boceprevir is described. This approach efficiently provides P1 fragment of boceprevir using simple and easy handling reagents suitable for scale up. This synthetic route involves the conversion of ester intermediate into novel intermediate, α-chloro ketone via chloroacetate Claisen condensation, followed by further simple conversions to β-amino-α-hydroxy amide, P1 fragment of boceprevir in high yield.

PROCESS FOR PREPARATION OF BOCEPREVIR AND INTERMEDIATES THEREOF

THE PRESENT INVENTION RELATES TO AN IMPROVED PROCESS FOR THE PREPARATION OF (1R,5S)-N-[3-AMINO-1-(CYCLOBUTYLMETHYL)-2,3-DIOXOPROPYL]-3-[2(S)-[[[(1,1-DIMETHYLETHYL)AMINO]CARBONYL] AMINO]-3,3-DIMETHYL-1-OXOBUTYL]-6,6-DIMETHYL-3-AZABICYCLO[3.1.0]HEXAN-2(S)-CARBOXAMIDE AND ITS INTERMEDIATES

PROCESS AND INTERMEDIATES FOR THE PREPARATION OF 3-AMINO-4-CYCLOBUTYL-2-HYDROXYBUTANAMIDE AND SALTS THEREOF

The present invention relates to synthetic processes useful in the preparation of a compound of Formula (I), and salts thereof. Compounds of Formula (I) and salts thereof have application in the preparation of inhibitors of the hepatitis C virus, such as (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6, 6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.

PROCESS FOR THE SYNTHESIS OF 3-AMINO-3-CYCLOBUTYLMETHYL-2-HYDROXYPROPIONAMIDE OR SALTS THEREOF

A process for preparing 3-amino-3-cyclobutylmethyl-2-hydroxypropionamide of the Formula I: [Chemical formula should be inserted here as it appears in the paper abstract.] or a salt thereof involves providing a compound of the Formula VI described herein in a solution comprising predominately dimethylsulfoxide (DMSO) and converting this compound directly to the compound of the Formula VIII described herein without working up or isolating the intermediate compound of the Formula VII described herein.

Pharmaceutical formulations and methods of treatment using the same

Pharmaceutical formulations containing at least one compound of Formulae I-XXVI herein and at least one surfactant. Pharmaceutically acceptable carriers and excipients may also be included in the formulations. The formulations of the present invention are suited for use in single unit dosages.

Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6, 6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavailable hepatitis C virus NS3 protease inhibitor: A potential therapeutic agent for the treatment of hepatitis C infection

Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-α or polyethylene glycol (PEG)-interferon-α alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.

Methods of treating hepatitis C virus

Methods for preventing, ameliorating or treating one or more symptoms of Hepatitis C virus (HCV), modulating HCV protease activity and/or inhibiting cathepsin activity in a subject, wherein the methods comprise administering to a subject in need of such treatment a dosage formulation containing at least one compound of Formulae I-XXVI herein, wherein the dosage formulation is capable of maintaining an average Cmin plasma concentration of the compound at or above 10 ng/ml.

Controlled-release formulation

Controlled-release dosage formulations including at least one compound of Formulae I to XXVI herein and a controlled-release carrier and methods of treatment using the same are provided.

Methods for treating hepatitis C

Methods of treating hepatitis C are provided comprising using a therapeutically effective amount of at least one novel hepatitis C (“HCV”) protease inhibitor or, alternatively, at least one antiviral or immuno-modulating HCV agent, which is not an HCV protease inhibitor, for a first treatment period. Subsequently, a combination of the at least one novel hepatitis C (“HCV”) protease inhibitor and the at least one antiviral or immuno-modulating HCV agent are administered in a therapeutically effective amount for a second treatment period. The methods are provided for treating a wide variety of diseases, disorders and symptoms associated with hepatitis C virus by modulating the activity of HCV protease (for example HCV NS3/NS4a serine protease) in a subject.

Methods of treating hepatitis C virus

Compositions and therapeutic combinations are provided including at least one compound selected from the group consisting of compounds of Formulae I to XXVI as defined herein as well as methods of treatment, prevention or amelioration of one or more symptoms of hepatitis C, treating disorders associated with HCV virus, modulating activity of HCV protease, or inhibiting cathepsin activity in a subject using the same, in which the mean volume of distribution/bioavailability (Vd/F) of the compound as measured in the plasma of the subject is greater than about 1000 L.