1174930-71-2Relevant academic research and scientific papers
An Efficient Synthesis of Ivacaftor
Zhang, Rui,Han, Guanyu,Jiang, Luobin,Shen, Yao,Yang, Rui,Mao, Yongjun,Wang, Hang
, p. 3169 - 3173 (2017)
New and practical synthetic route of ivacaftor is described on a grams scale. An electrophilic addition of two t-butyl groups to the aromatic ring is adopted to prepare 5-amino-2,4-di-t-butylphenol in 61% yield over three steps with 98.1% purity (high-performance liquid chromatography). An intramolecular cyclization of ethyl 3-(2-aminophenyl)-3-oxo-propanoate with dimethylformamide-dynamic mechanical analysis is used to prepare 4-oxo-1,4-dihydroquinoline-3-carboxylic acid in 54% yield over four steps. Ivacaftor is obtained by condensation of the two parts in 71% yield with 99.1% purity (high-performance liquid chromatography).
Utilizing o-Quinone Methide Chemistry: Synthesis of d9-Ivacaftor
Lewandowski, Bérénice L.,Looker, Adam R.,Roeper, Stefanie,Ryan, Michael P.,Wilde, Nathan,Ye, Zhifeng
, (2020)
Lead time and cost are important factors for any pharmaceutical API. However, these issues become even more important when the drug substance contains an isotope such as deuterium, which has a natural abundance of only ～0.016% of all hydrogen. Fewer suppliers and logistical barriers both play a role in driving up the cost. These factors can challenge the supply route used to manufacture d9-ivacaftor (17), requiring investigation into alternative routes. By adapting the work from Pettus et al., a synthetic approach utilizing a transient o-quinone methide allowed access to the deuterium-labeled o-tert-butylphenol moiety. This was developed and proven on pilot scale to significantly reduce the number of deuterated reagents used, leading to an overall reduction in cost by a factor of 10, while also providing the substantial benefit of applying prior process knowledge from the parent, nonisotopically enriched API ivacaftor (7).
Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases
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, (2021/04/21)
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.
METHODS OF TREATMENT FOR CYSTIC FIBROSIS
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, (2020/06/05)
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
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, (2020/12/11)
This application describes methods of treating cystic fibrosis comprising administering Compound I:, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing.
COMPOSITIONS AND METHODS FOR TREATMENT OF CYSTIC FIBROSIS
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, (2019/01/22)
Compositions comprising Compound I of the formula (I) and methods of treating cystic fibrosis comprising administering Compound I. Compositions comprising a pharmaceutically acceptable salt of Compound I and methods of treating cystic fibrosis comprising administering a pharmaceutically acceptable salt of Compound I.
COMPOSITIONS FOR TREATING CYSTIC FIBROSIS
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, (2019/06/23)
A single tablet comprising Compound I:. Methods of treating cystic fibrosis comprising administering one or more of such single tablets to a patient.
METHODS OF TREATMENT FOR CYSTIC FIBROSIS
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, (2019/02/06)
Methods of treating cystic fibrosis comprising administering at least Compound (I) of the formula. Pharmaceutical compositions containing a pharmaceutically acceptable salt of at least Compound I and methods of treating cystic fibrosis comprising administering a pharmaceutically acceptable salt of at least Compound (I).
METHODS OF TREATMENT FOR CYSTIC FIBROSIS
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, (2019/02/06)
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.
CRYSTALLINE FORMS AND COMPOSITIONS OF CFTR MODULATORS
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, (2019/05/07)
Crystalline Forms of Compound I: and pharmaceutically acceptable salts thereofare disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed.
