68119-31-3

Usage

Uses

Used in Pharmaceutical Industry:
2-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)acetonitrile is used as a building block for the synthesis of various biologically active compounds, contributing to the development of new pharmaceuticals.
Used in Agrochemicals:
In the agrochemical industry, 2-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)acetonitrile is used as a precursor in the synthesis of agrochemicals, potentially enhancing crop protection and yield.
Used in Materials Research:
2-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)acetonitrile is utilized in materials research for the development of new materials with specific properties, such as improved stability or reactivity.
Used in Biological Research:
2-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)acetonitrile is employed in biological research for studying its potential biological properties, such as hERG channel blocking activity and anticoagulant properties, which may lead to the discovery of new therapeutic agents.
Used in Drug Development:
As a compound with potential biological properties, 2-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)acetonitrile is used in drug development for the creation of new pharmaceuticals with targeted therapeutic effects.

Upstream product

• 476473-97-9 5-chloromethyl-2,2-difluoro-benzo[1,3]dioxole 
• 1634-04-4 tert-butyl methyl ether 
• 33070-32-5 5-bromo-2,2-difluoro-2H-1,3-benzodioxole 
• 656-46-2 2,2-difluoro-1,3-benzodioxole-5-carboxylic acid 
• 105-56-6 ethyl 2-cyanoacetate 
• 1583-59-1 2,2-difluoro-1,3-benzodioxole 
• 773837-37-9 sodium cyanide 
• 72768-97-9 (2,2-difluoro-1,3-benzodioxol-5-yl)methanol 
• 68119-28-8 2,2-dichloro-5-methyl-1,3-benzodioxole 
• 7145-99-5 5-methyl-1,3-benzodioxole 
• 1335233-51-6 (2,2-difluoro-1,3-benzodioxol-5-yl)-1-ethylacetate acetonitrile 
• 773873-95-3 2,2-difluorobenzo[1,3]dioxole-5-carboxylic acid methyl ester 
• 143-33-9 sodium cyanide 

Downstream Products

• 862574-88-7 1-(2,2-difluorobenzo[1,3]dioxol-5-yl)cyclopropane-1-carboxylic acid 
• 1152311-62-0 (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide 
• 1294504-68-9 N-{1-[(2R)-3-(benzyloxy)-2-hydroxypropyl]-2-[1-(benzyloxy)-2-methylpropan-2-yl]-6-fluoro-1H-indol-5-yl}-1-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)cyclopropane-1-carboxamide 
• 862574-87-6 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarbonitrile 
• 1152274-48-0 2-(3-(3-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane carboxamido)isoquinolin-1-yl)benzoyloxy)-N,N,N-trimethylethanaminium chloride 
• 1152274-36-6 2-(dimethylamino)ethyl 3-(3-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)isoquinolin-1-yl)benzoate 
• 1152274-55-9 tert-butyl 3-(3-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)isoquinolin-1-yl)benzoate 
• 1152274-47-9 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(4-(hydroxymethyl)phenyl)isoquinolin-3-yl)cyclopropanecarboxamide 
• 1152274-56-0 3-(3-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)isoquinolin-1-yl)benzoyl chloride 
• 1083168-21-1 N-(6-(1-(2-cyanamido-2-oxoethyl)-6-oxo-1,6-dihydropyridin-3-yl)-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide 
• 1083168-23-3 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6-(5-fluoro-2-oxo-1,2-dihydropyridin-4-yl)-5-methylpyridin-2-yl)cyclopropanecarboxamide 
• 1160221-26-0 Lumacaftor hydrochloride 
• 936727-05-8 Lumacaftor 

Relevant academic research and scientific papers

Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases

The present invention features compositions comprising a plurality of therapeutic agents wherein the presence of one therapeutic agent enhances the properties of at least one other therapeutic agent. In one embodiment, the therapeutic agents are cystic fibrosis transmembrane conductance regulators (CFTR) such as a CFTR corrector or CFTR potentiator for the treatment of CFTR mediated diseases such as cystic fibrosis. Methods and kits thereof are also disclosed.

Assembly of α-(Hetero)aryl Nitriles via Copper-Catalyzed Coupling Reactions with (Hetero)aryl Chlorides and Bromides

α-(Hetero)aryl nitriles are important structural motifs for pharmaceutical design. The known methods for direct synthesis of these compounds via coupling with (hetero)aryl halides suffer from narrow reaction scope. Herein, we report that the combination of copper salts and oxalic diamides enables the coupling of a variety of (hetero)aryl halides (Cl, Br) and ethyl cyanoacetate under mild conditions, affording α-(hetero)arylacetonitriles via one-pot decarboxylation. Additionally, the CuBr/oxalic diamide catalyzed coupling of (hetero)aryl bromides with α-alkyl-substituted ethyl cyanoacetates proceeds smoothly at 60 °C, leading to the formation of α-alkyl (hetero)arylacetonitriles after decarboxylation. The method features a general substrate scope and is compatible with various functionalities and heteroaryls.

METHODS OF TREATMENT FOR CYSTIC FIBROSIS

This application describes methods of treating cystic fibrosis or a CFTR mediated disease comprising administering Compound I or a pharmaceutically acceptable salt thereof. (I) The application also describes pharmaceutical compositions comprising Compound I or a pharmaceutically acceptable salt thereof and optionally comprising one or more additional CFTR modulating agents.

METHODS OF TREATMENT FOR CYSTIC FIBROSIS

Compound I of the formula (I) and/or pharmaceutically acceptable salt(s) of Compound I comprised in a pharmaceutical composition and methods of using the same to treat cystic fibrosis.

1 - (2, 2 - Difluorobenzene and [D] [1, 3] dioxo heterocyclic pentene -5 - yl) ring propyl nitrile of preparation method

The invention discloses a preparation method for 1-(2,2-difluoro-benzo[D][1,3]dioxol-5-yl)-cyclopropanecarbonitrile. The method comprises the following steps: 5-(chloromethyl)benzo[d][1,3]dioxole is prepared from 2,2-difluoro-1,3-benzodioxole through Blanc chloromethylation, and then is subjected to cyanation by utilization of cuprous cyanide, finally cyclization is carried out by utilization of 1-Bromo-2-chloroethane and a product is obtained. In the above method, cyanation is carried out by utilization of low-toxic cuprous cyanide, a weak organic base triethylamine deacid reagent is employed to carry out cyclization preparation and a target product is obtained, usage of dangerous lithium aluminum hydride and sodium cyanide is avoided, strong alkaline and high temperature conditions are avoided, and therefore hydrolysis of cyan in the product is avoided. The preparation method is low-toxic to the environment and the product yield and quality are raised. The process flow is simple and safe, the reaction process is easy to control, the cost is low, the yield is high, and the preparation method is suitable for industrialization.

PHARMACEUTICAL COMPOSITIONS OF 3-(6-(1-(2,2-DIFLUOROBENZO[D][1,3]DIOXOL-5-YL)CYCLOPROPANECARBOXAMIDO)-3-METHYLPYRIDIN-2-YL)BENZOIC ACID AND ADMINISTRATION THEREOF

A pharmaceutical composition comprising Compound 1,(3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a diluent, a disintegrant, a surfactant, a binder, a glidant and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Methods for treating a patient in need thereof include administering an oral pharmaceutical formulation of Compound 1 to the patient.

MODULATOR OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR, PHARMACEUTICAL COMPOSITIONS, METHODS OF TREATMENT, AND PROCESS FOR MAKING THE MODULATOR

Compounds of Formula (I) pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed. Also disclosed are solid state forms of Compound 1 and salts and solvates thereof.

Synthesis and biological evaluation of novel thiazole- VX-809 hybrid derivatives as F508del correctors by QSAR-based filtering tools

The most common CF mutation, F508del, impairs the processing and gating of CFTR protein. This deletion results in the improper folding of the protein and its degradation before it reaches the plasma membrane of epithelial cells. Present correctors, like VX809 only induce a partial rescue of the mutant protein. Our previous studies reported a class of compounds, called aminoarylthiazoles (AATs), featuring an interesting activity as correctors. Some of them show additive effect with VX809 indicating a different mechanism of action. In an attempt to construct more interesting molecules, it was thought to generate chemically hybrid compounds, blending a portion of VX809 merged to the thiazole scaffold. This approach was guided by the development of QSAR analyses, which were performed based on the F508del correctors so far disclosed in the literature. This strategy was aimed at exploring the key requirements turning in the corrector ability of the collected derivatives and allowed us to derive a predictive model guiding for the synthesis of novel hybrids as promising correctors. The new molecules were tested in functional and biochemical assays on bronchial CFBE41o-cells expressing F508del-CFTR showing a promising corrector activity.

DEUTERATED CFTR MODULATORS AND METHODS OF USE

The invention discloses compounds of Formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, A, R19, R20, and R21 are as defined herein. The present invention relates to deuterated compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.

FORMULATIONS OF 3-(6-(1-(2,2-DIFLUOROBENZO[D][1,3]DIOXOL-5-YL) CYCLOPROPANECARBOXAMIDO)-3-METHYLPYRIDIN-2-YL)BENZOIC ACID

A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a disintegrant, a surfactant, a binder, and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Processes of preparing pharmaceutical compositions comprising Compound 1 are also disclosed.