Ivacaftor

Base Information

• Chemical Name: Ivacaftor
• CAS No.: 873054-44-5
• Deprecated CAS: 1174930-71-2,1134822-00-6
• Molecular Formula: C24H28N2O3
• Molecular Weight: 392.498
• Hs Code.: 29333990
• European Community (EC) Number: 800-027-5
• UNII: 1Y740ILL1Z
• ChEMBL ID: CHEMBL2010601
• DSSTox Substance ID: DTXSID00236281
• Metabolomics Workbench ID: 43729
• NCI Thesaurus Code: C166523
• Nikkaji Number: J3.163.539J
• Pharos Ligand ID: S91W36X1YGJK
• RXCUI: 1243041
• Wikidata: Q6095693
• Wikipedia: Ivacaftor
• Mol file: 873054-44-5.mol

Synonyms:3-quinolinecarboxamide, N-(2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl)-1,4-dihydro-4-oxo-;ivacaftor;Kalydeco;N-(2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide;N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide;VX-770

Chemical Property of Ivacaftor

Chemical Property:

• Vapor Pressure: 1E-12mmHg at 25°C
• Refractive Index: 1.605
• Boiling Point: 550.4 °C at 760 mmHg
• PKA: 11.08±0.23(Predicted)
• Flash Point: 286.7 °C
• PSA: 85.68000
• Density: 1.187 g/cm³
• LogP: 5.46500
• Storage Temp.: Refrigerator
• Solubility.: DMSO (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)
• XLogP3: 5.6
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 4
• Exact Mass: 392.20999276
• Heavy Atom Count: 29
• Complexity: 671

Purity/Quality:

99%, ^*data from raw suppliers

Ivacaftor ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)(C)C1=CC(=C(C=C1NC(=O)C2=CNC3=CC=CC=C3C2=O)O)C(C)(C)C
• Recent ClinicalTrials: The Topic Trial - Study to Determine the Safety and Efficacy of Ivacaftor
• Recent EU Clinical Trials: A Phase 3 Study Evaluating the Pharmacokinetics, Safety, and Tolerability of VX-121/Tezacaftor/Deutivacaftor Triple Combination Therapy in Cystic Fibrosis Subjects 1 Through 11 Years of Age
• Description: In January 2012, the US FDA approved ivacaftor for the treatment of cystic fibrosis (CF) in patients who have the G551D mutation of the CF transmembrane regulator (CFTR) and are at least 6 years old. Ivacaftor (also known as VX-770) is a CFTR potentiator that increases the open probability of CFTR, thus increasing chloride secretion particularly in the 5% of CF patients with the G551D/F508 gating/ processing mutation. Ivacaftor was discovered by medicinal chemistry optimization of a lead scaffold identified through high-throughput screening of a 228,000 compound collection. In cultured bronchial epithelial cells from a CF patient with F508del, ivacaftor increased chloride secretion (EC50=81 nM). Preparation of ivacaftor is accomplished via a multistep synthesis oftwointermediates, 4-oxo-1,4-dihydroquinoline-3-carboxylic acid and 5-amino-di-tert-butylphenyl methyl carbonate, which are coupled using propane phosphonic acid anhydride (T3P) to afford the amide; deprotection of the phenol then provides ivacaftor.
• Uses: Ivacaftor (VX-770, Kalydeco) is a potentiator of CFTR targeting G551D-CFTR and F508del-CFTR with EC50 of 100 nM and 25 nM, respectively Ivacaftor is used in the treatment of cystic fibrosis.
• Clinical Use: Vertex’s ivacaftor was granted breakthrough therapy designation by the FDA in January 2012 for cystic fibrosis (CF) patients who bear the G551D mutation in the Cycstic Fibrosis Transmembrane Regulator (CFTR) gene. This CFTR mutation occurs in roughly 4% of the 30,000 people living with CF in the United States. While the compound has been identified as a potentiator in cell-based assays, its mechanism of action is as yet unknown.

Technology Process of Ivacaftor

There total 58 articles about Ivacaftor 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: 88.0%

C24H27ClN2O2 → ivacaftor (873054-44-5,1174930-71-2)

Guidance literature:

With hydrogenchloride; In water; acetonitrile; at 75 - 85 ℃; for 6h;

Reference yield: 87.0%

C24H27BrN2O2 → ivacaftor (873054-44-5,1174930-71-2)

Guidance literature:

With hydrogenchloride; In water; acetonitrile; at 75 - 85 ℃; for 6h;

Reference yield: 80.0%

C31H34N2O3 → ivacaftor (873054-44-5,1174930-71-2)

Guidance literature:

With 5%-palladium/activated carbon; hydrogen; In methanol; at 35 ℃; for 5h; under 1520.1 Torr; Temperature; Pressure;

upstream raw materials:

5-amino-2-4-di-tert-butyl-phenol

2,4-di-tert-butyl-5-(4-oxo-1,4-dihydroquinoline-3-carboxamido)phenyl methyl carbonate

3-methyl-4-nitro-1H-indole

5-amino-2,4-di-tert-butylphenyl methyl carbonate

Downstream raw materials:

N-(5-hydroxy-2,4-ditert-butyl-phenyl)-5-methyl-4-oxo-1H-quinoline-3-carboxamide

N-(2-(tert-butyl)-5-hydroxy-4-(1-hydroxy-2-methylpropan-2-yl)phenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide

2-(5-tert-butyl-2-hydroxy-4-(4-oxo-1,4-dihydroquinoline-3-carboxamido)phenyl)-2-methylpropanoic acid

N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.besylate

Refernces

• 1、 Lewandowski, Bérénice L.,Looker, Adam R.,Roeper, Stefanie,Ryan, Michael P.,Wilde, Nathan,Ye, Zhifeng. "Utilizing o-Quinone Methide Chemistry: Synthesis of d9-Ivacaftor". . . Retrieved 2020/01/22.
• 2、 -. "METHODS OF TREATMENT FOR CYSTIC FIBROSIS". . . Retrieved 2020/12/11.