565456-75-9

Usage

Uses

Used in Pharmaceutical Research:
BOC-DL-CYCLOBUTYLALANINE is used as a synthetic building block for the development of peptides with specific properties. Its incorporation into peptide structures allows for the exploration of new therapeutic agents and the enhancement of existing ones, contributing to the advancement of medicinal chemistry.
Used in Biochemistry:
In the field of biochemistry, BOC-DL-CYCLOBUTYLALANINE is utilized as a research tool to study the effects of structural modifications on peptide and protein function. This aids in understanding the fundamental principles of protein structure and function, which is crucial for the development of new bioactive compounds and the elucidation of biological processes.
Used in Peptide Synthesis:
BOC-DL-CYCLOBUTYLALANINE is used as a protected amino acid in the synthesis of peptides. The BOC group protects the amino group during the synthesis process, allowing for the stepwise addition of other amino acids without unwanted side reactions. This results in the production of peptides with high purity and specific sequences, which are essential for various applications in research and medicine.

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 394735-17-2 ethyl 2-amino-3-cyclobutylpropanoate 
• 17247-58-4 (Bromomethyl)cyclobutane 
• 1025799-39-6 2-(benzhydrylidene-amino)-3-cyclobutyl-propionic acid ethyl ester 
• 816430-02-1 ethyl 2-(tert-butoxycarbonylamino)-3-cyclobutylpropanoate 

Downstream Products

• 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 
• 1036931-36-8 3-amino-4-cyclobutyl-2-hydroxybutanamide hydrochloride 
• 394735-22-9 tert-butyl 4-amino-1-cyclobutyl-3-hydroxy-4-oxobutan-2-ylcarbamate 
• 394730-60-0 boceprevir 
• 394735-20-7 (2-cyano-1-cyclobutylmethyl-2-hydroxyethyl)carbamic acid tert-butyl ester 
• 394735-19-4 (2-cyclobutyl-1-formylethyl)carbamic acid tert-butyl ester 
• 394735-18-3 tert-butyl 3-cyclobutyl-1-(methoxy(methyl)amino)-1-oxopropan-2-ylcarbamate 

Relevant academic research and scientific papers

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

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.

Liver/plasma concentration ratio for dosing hepatitis C virus protease inhibitor

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, in which liver to plasma concentration ratio of the compound ranges from about 2:1 to about 10:1.

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.

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 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.

Medicaments and methods combining a HCV protease inhibitor and an AKR competitor

Disclosed are medicaments, pharmaceutical compositions, pharmaceutical kits, and methods based on combinations of a hepatitis C virus (HCV) protease inhibitor and an aldo-keto reductase (AKR) competitor, for concurrent or consecutive administration in treating, preventing, or ameliorating one or more symptoms of HCV, treating disorders associated with HCV, or inhibiting cathepsin activity in a subject.

Administration of HCV protease inhibitors in combination with food to improve bioavailability

Methods of treating, preventing or ameliorating one or more symptoms of hepatitis C in a subject comprising the step of administering at least one HCV protease inhibitor in combination with food are provided. Also provided are methods of increasing bioavailability of an HCV protease inhibitor and methods of increasing serum levels of an HCV protease inhibitor in a subject. All methods comprise adminstering at least one HCV protease inhibitor in combination with food, the at least one HCV protease inhibitor selected from the group consisting of compounds of Formulae I-XXVI, described herein. Administration of compounds of the present invention in combination with food provides improved bioavailability and increased peak serum levels of the compounds as compared to administration without food.