779206-51-8Relevant academic research and scientific papers
Modulators of the Cystic Fibrosis Transmembrane Conductance Regulator Protein and Methods of Use
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Paragraph 2152, (2019/03/30)
The invention discloses compounds of Formula (I), wherein A1, R1, R2, R3, R4, and n are as defined herein. The present invention relates to 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.
Electrophilic Bromolactonization of Cyclopropyl Diesters Using Lewis Basic Chalcogenide Catalysts
Gieuw, Matthew H.,Leung, Vincent Ming-Yau,Ke, Zhihai,Yeung, Ying-Yeung
, p. 4306 - 4311 (2018/10/02)
An efficient and regioselective electrophilic bromolactonization of cyclopropylmethyl diesters using triphenylphosphine sulfide (Ph3PS) or diphenyl selenide (Ph2Se) as the Lewis basic chalcogenide catalyst has been developed. It was observed that Ph3PS favored the formation of anti-diastereomer and yielded the multi-functional γ-lactones. Interestingly, the diastereoselectivity was reversed when using Ph2Se as a catalyst where the syn-product instead of the anti-product was favored. (Figure presented.).
Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
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Paragraph 1122; 1529; 1578, (2015/09/22)
The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
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, (2012/04/23)
The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
Modulators of ATP-binding cassette transporters
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Page/Page column 383, (2008/06/13)
Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.
One-electron oxidation of 2-(4-methoxyphenyl)-2-methylpropanoic and 1-(4-methoxyphenyl)cyclopropanecarboxylic acids in aqueous solution. The involvement of radical cations and the influence of structural effects and pH on the side-chain fragmentation reactivity
Bietti, Massimo,Capone, Alberto
, p. 618 - 629 (2008/09/18)
(Chemical Equation Presented) A product and time-resolved kinetic study on the one-electron oxidation of 2-(4-methoxyphenyl)-2-methylpropanoic acid (2), 1-(4-methoxyphenyl)cyclopropanecarboxylic acid (3), and of the corresponding methyl esters (substrates 4 and 5, respectively) has been carried out in aqueous solution. With 2, no direct evidence for the formation of an intermediate radical cation 2?+ but only of the decarboxylated 4-methoxycumyl radical has been obtained, indicating either that 2?+ is not formed or that its decarboxylation is too fast to allow detection under the experimental conditions employed (k > 1 × 107 s -1). With 3, oxidation leads to the formation of the corresponding radical cation 3?+ or radical zwitterion -3 ?+ depending on pH. At pH 1.0 and 6.7, 3?+ and -3?+ have been observed to undergo decarboxylation as the exclusive side-chain fragmentation pathway with rate constants k = 4.6 × 103 and 2.3 × 104 s-1, respectively. With methyl esters 4 and 5, direct evidence for the formation of the corresponding radical cations 4?+ and 5?+ has been obtained. Both radical cations have been observed to display a very low reactivity and an upper limit for their decay rate constants has been determined as k 3 s-1. Comparison between the one-electron oxidation reactions of 2 and 3 shows that the replacement of the C(CH3)2 moiety with a cyclopropyl group determines a decrease in decarboxylation rate constant of more than 3 orders of magnitude. This large difference in reactivity has been qualitatively explained in terms of three main contributions: substrate oxidation potential, stability of the carbon-centered radical formed after decarboxylation, and stereoelectronic effects. In basic solution, -3?+ and 5 ?+ have been observed to react with -OH in a process that is assigned to the -OH-induced ring-opening of the cyclopropane ring, and the corresponding second-order rate constants (k-OH) have been obtained. With -3?+, competition between decarboxylation and -OH-induced cyclopropane ring-opening is observed at pH ≥ 10, with the latter process that becomes the major fragmentation pathway around pH 12.
Modulators of ATP-binding cassette transporters
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Page/Page column 81-82, (2008/06/13)
Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.
