873055-56-2Relevant articles and documents
METHODS OF TREATMENT FOR CYSTIC FIBROSIS
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Paragraph 00119, (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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Paragraph 00230, (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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Paragraph 00324; 00325; 00333; 00336; 00337, (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.
METHODS OF TREATMENT FOR CYSTIC FIBROSIS
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Paragraph 00180, (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.
Evaluation of 1,2,3-Triazoles as Amide Bioisosteres In Cystic Fibrosis Transmembrane Conductance Regulator Modulators VX-770 and VX-809
Doiron, Jake E.,Le, Christina A.,Ody, Britton K.,Brace, Jonathon B.,Post, Savannah J.,Thacker, Nathan L.,Hill, Harrison M.,Breton, Gary W.,Mulder, Matthew J.,Chang, Sichen,Bridges, Thomas M.,Tang, Liping,Wang, Wei,Rowe, Steven M.,Aller, Stephen G.,Turlington, Mark
supporting information, p. 3662 - 3674 (2019/02/19)
The 1,2,3-triazole has been successfully utilized as an amide bioisostere in multiple therapeutic contexts. Based on this precedent, triazole analogues derived from VX-809 and VX-770, prominent amide-containing modulators of the cystic fibrosis transmembrane conductance regulator (CFTR), were synthesized and evaluated for CFTR modulation. Triazole 11, derived from VX-809, displayed markedly reduced efficacy in F508del-CFTR correction in cellular TECC assays in comparison to VX-809. Surprisingly, triazole analogues derived from potentiator VX-770 displayed no potentiation of F508del, G551D, or WT-CFTR in cellular Ussing chamber assays. However, patch clamp analysis revealed that triazole 60 potentiates WT-CFTR similarly to VX-770. The efficacy of 60 in the cell-free patch clamp experiment suggests that the loss of activity in the cellular assay could be due to the inability of VX-770 triazole derivatives to reach the CFTR binding site. Moreover, in addition to the negative impact on biological activity, triazoles in both structural classes displayed decreased metabolic stability in human microsomes relative to the analogous amides. In contrast to the many studies that demonstrate the advantages of using the 1,2,3-triazole, these findings highlight the negative impacts that can arise from replacement of the amide with the triazole and suggest that caution is warranted when considering use of the 1,2,3-triazole as an amide bioisostere.
METHODS OF TREATMENT FOR CYSTIC FIBROSIS
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Paragraph 00149, (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).
COMPOSITIONS FOR TREATING CYSTIC FIBROSIS
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Paragraph 00247, (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.
PROCESSES FOR MAKING MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR
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Paragraph 00253, (2019/06/17)
The disclosure provides processes for synthesizing compounds for use as CFTR modulators.
CRYSTALLINE FORMS AND COMPOSITIONS OF CFTR MODULATORS
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Paragraph 0516; 0518, (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.
CRYSTALLINE FORMS OF MODULATORS OF CFTR
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Paragraph 00428, (2019/10/19)
Crystalline Forms of Compound (I); crystalline Forms of Compound (II) and crystalline forms of pharmaceutically acceptable salts 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.
