936727-05-8

Basic information

• Product Name: Lumacaftor (VX-809)
• Synonyms: 3-(6-{[1-(2,2-Difluorobenzo[1,3]dioxol-5-yl)cyclopropanecarbonyl]-amino}-3-methyl-pyridin-2-yl)be;VX-809 (LuMacaftor);3-[6-[[[1-(2,2-Difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl]amino]-3-methyl-2-pyridinyl]benzoic acid VX 809 Lumacaftor;3-(6-{[1-(2;Lumacaftor VX809;VX 809, >=98%;VX-809, Lumacaftor, VRT 826809;3-[6-[[1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropanecarbonyl]amino]-3-methylpyridin-2-yl]benzoic acid
• CAS NO: 936727-05-8
• Molecular Formula: C24H18F2N2O5
• Molecular Weight: 452.4069264
• Product Categories: VX-809;Inhibitors
• Mol File: 936727-05-8.mol

Chemical Properties

• Boiling Point: 653.013 °C at 760 mmHg
• Flash Point: 348.73 °C
• Appearance: /
• Density: 1.51
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.67
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 3.95±0.10(Predicted)
• CAS DataBase Reference: Lumacaftor (VX-809)(CAS DataBase Reference)
• NIST Chemistry Reference: Lumacaftor (VX-809)(936727-05-8)
• EPA Substance Registry System: Lumacaftor (VX-809)(936727-05-8)

Safety Data

• Hazardous Substances Data: 936727-05-8(Hazardous Substances Data)

Usage

Uses

VX 809 is used in the stabilization of the CFTR protein used in the treatment of cystic fibrosis.

Definition

ChEBI: An aromatic amide obtained by formal condensation of the carboxy group of 1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropane-1-carboxylic acid with the aromatic amino group of 3-(6-amino-3-methylpyridin-2-yl)benzoic acid. Used for the treatment of cystic fi rosis.

Biological Activity

vx-809 is a cftr corrector that partially restores the function of f508del-cftr. in fischer rat thyroid (frt) cells, it increases f508del-cftr maturation at ec50 of 0.1 μm, and elevates f508del-cftr–mediated chloride transport at ec50 of 0.5 μm [1]. it has no effect of other ion channels (herg), transporter (p-gp) and disease-causing mislocalized proteins (α1-antitrypsin z mutant) [1]. vx-809 stabilizes n-terminal fragment of cftr that contain msd1 by altering its protein conformation [2, 3].homozygous f508del-cftr is the most common mutation in cystic fibrosis (cf) patients, accounting for 66–70% of cf cases worldwide. in cultured human bronchial epithelial cells that are homozygous for f508del, vx-809 restored the cftr function and improved chloride and fluid transport [1]. the combination of cftr potentiators and vx-809 further improved the function of f508del-cftr [4].vx-809 has been tested in several

InChI:InChI=1/C24H18F2N2O5/c1-13-5-8-19(27-20(13)14-3-2-4-15(11-14)21(29)30)28-22(31)23(9-10-23)16-6-7-17-18(12-16)33-24(25,26)32-17/h2-8,11-12H,9-10H2,1H3,(H,29,30)(H,27,28,31)

Upstream product

• 1160221-26-0 Lumacaftor hydrochloride 
• 1160221-25-9 tert-butyl 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamido)-3-methylpyridin-2-yl)benzoate 
• 3430-17-9 2-bromo-3-picoline 
• 1083057-12-8 tert-butyl 3-(3-methylpyridin-2-yl)benzoate 
• 1083057-13-9 tert-butyl 3-(3-methyl-1-oxo-1λ-pyridin-2-yl)benzoate 
• 1083057-14-0 tert-butyl 3-(6-amino-3-methylpyridin-2-yl)benzoate 
• 476473-97-9 5-chloromethyl-2,2-difluoro-benzo[1,3]dioxole 
• 1335233-51-6 (2,2-difluoro-1,3-benzodioxol-5-yl)-1-ethylacetate acetonitrile 
• 33070-32-5 5-bromo-2,2-difluoro-2H-1,3-benzodioxole 
• 862574-87-6 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarbonitrile 
• 862574-88-7 1-(2,2-difluorobenzo[1,3]dioxol-5-yl)cyclopropane-1-carboxylic acid 
• 1004294-65-8 1-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)cyclopropane carboxylic acid chloride 
• 656-46-2 2,2-difluoro-1,3-benzodioxole-5-carboxylic acid 
• 68119-31-3 2-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)acetonitrile 

Relevant articles and documents

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.

PROCESS AND CRYSTALLINE FORMS OF LUMACAFTOR

The present invention generally relates to crystalline forms of Lumacaftor, processes for its preparation and pharmaceutical compositions thereof. The present invention also relates to an improved process for preparation of Lumacaftor.

PROCESS FOR THE PREPARATION OF LUMACAFTOR

The present disclosure relates to processes for the preparation of lumacaftor useful for treating a cystic fibrosis transmembrane conductance regulator (CFTR)-mediated disease such as cystic fibrosis. The present disclosure also provides intermediates useful in the preparation of lumacaftor

PROCESS FOR PREPARATION OF LUMACAFTOR

The present invention relates to a process for the preparation of amorphous lumacaftor. The present invention relates to a process for the preparation of intermediate 6-amino-2- halo-3-methylpyridine compounds used in the preparation of lumacaftor. The present invention relates to lumacaftor hydrobromide, process for its preparation and conversion thereof to lumacaftor.

SOLID FORMS OF LUMACAFTOR, ITS SALTS AND PROCESSES THEREOF

Aspects of the present application relate to solid forms of Lumacaftor, its salts and processes thereof. Specific aspects of the present application relate to alternate processes for the preparation of Lumacaftor and intermediates thereof. Present application further relates to the solid forms of Lumacaftor and its salts.

AMORPHOUS LUMACAFTOR AND ITS SOLID DISPERSION

The present invention provides a novel amorphous form of lumacaftor and its preparation by various methods. The patent invention also relates to novel lumacaftor hydrobromide crystalline form A and process for its preparation. The present invention relates to amorphous lumacaftor premixed with an excipient and process for the preparation of the premix.

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.

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.

PROCESS OF PREPARING PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF CFTR MEDIATED DISEASES

Processes of preparing pharmaceutical compositions comprising 3-(6-(1-(2,2- difluorobenzo[d][1,3] dioxol-5 -yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Compound 1) in Form I and a solid dispersion comprising substantially amorphous N-(5- hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-lH-quinoline-3-carboxamide (Compound 2), methods of treating, lessening the severity of, or symptomatically treating CFTR mediated diseases, such as cystic fibrosis, methods of administering, and kits thereof are disclosed.

PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF CFTR MEDIATED DISEASES

Pharmaceutical compositions comprising 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5- yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Compound 1) in Form I and a solid dispersion comprising substantially amorphous N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4- oxo-1H-quinoline-3-carboxamide (Compound 2), methods of treating, lessening the severity of, or symptomatically treating CFTR mediated diseases, such as cystic fibrosis, methods of manufacturing, methods of administering, and kits thereof are disclosed.