- Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
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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.
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Paragraph 1569
(2015/09/22)
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- COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
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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.
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- MODULATORS OF CFTR
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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 CFTR mediated diseases using compounds of the present invention.
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Page/Page column 75
(2009/01/20)
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- Non-nucleoside reverse transcriptase inhibitors
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The present invention provides for compounds useful for treating an HIV-1 infection, or preventing an HIV-1 infection, or treating AIDS or ARC. The compounds of the invention are of formula I wherein R1-R4 and Ar are as herein defined. Also disclosed in t
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Page/Page column 19
(2010/11/26)
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- Modulators of ATP-binding cassette transporters
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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.
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Page/Page column 90
(2008/06/13)
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- Cyclopentadienyltricarbonylrheniumbenzazepines: Synthesis and binding affinity
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Analogues of the benzazepine dopamine D1 receptor antagonist SCH-23390 incorporating the cyclo-pentadienyltricarbonyl-rhenium (CPTR) moiety were synthesized and evaluated pharmacologically. The CPTR derivatives retained affinity (0.3-2.9 nM) an
- Tamagnan, Gilles,Baldwin, Ronald M.,Kula, Nora S.,Baldessarini, Ross J.,Innis, Robert B.
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p. 1113 - 1115
(2007/10/03)
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- Quantitative structure-activity relationship modeling of dopamine D1 antagonists using comparative molecular field analysis, genetic algorithms- partial least-squares, and K nearest neighbor methods
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Several quantitative structure-activity relationship (QSAR) methods were applied to 29 chemically diverse D1 dopamine antagonists. In addition to conventional 3D comparative molecular field analysis (CoMFA), cross-validated R2 guided
- Hoffman, Brian,Cho, Sung Jin,Zheng, Weifan,Wyrick, Steven,Nichols, David E.,Mailman, Richard B.,Tropsha, Alexander
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p. 3217 - 3226
(2007/10/03)
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- Synthesis and pharmacological characterization of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines as dopamine receptor ligands
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A series of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines have been prepared as ring-contracted analogues of the prototypical D1 dopamine receptor antagonist SCH23390 [(R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3 benzazepine]. The affinity and selectivity of these isoquinolines for D1 receptors was determined by three biochemical endpoints in membrane homogenates prepared from rat corpus striatum: the potency to compete for [3H]SCH23390 binding sites; the potency to compete for [3H]spiperone (a D2 receptor ligand) binding sites; and effects on dopamine-stimulated adenylate cyclase. Competitive binding measurements at D1 sites showed SCH23390 to possess the highest affinity, followed by 1-phenyl > 1-benzyl > 4-phenyl for the isoquinolines. These results were highly correlated with the ability of the test compounds to antagonize dopamine-stimulated adenylate cyclase (r = 0.98). None of the compounds alone stimulated cAMP formation at concentrations of 10 nM to 100 μM. D2 competition binding showed the 1-benzyl derivative to possess the highest affinity, followed by 4-phenyl > SCH23390 > 1-phenyl. The tertiary 1-phenyl derivative was more potent than the secondary 1-phenyl analogue in all assays. Interestingly, resolution and single-crystal X-ray analysis of the tertiary N-methyl-1-phenyltetrahydroisoquinoline showed the most active enantiomer to possess the S absolute configuration, in contrast to the benzazepine (R)-SCH23390.
- Charifson,Wyrick,Hoffman,Ademe Simmons,Bowen,McDougald,Mailman
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p. 1941 - 1946
(2007/10/02)
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- Antiinflammatory substituted phenylacetic acids
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Antiinflammatory substituted phenylacetic acids of low toxicity are prepared by reaction of a salt of an alkyl 3 chloro-4-hydroxyphenylacetate with a substituted benzyl halide in the presence of an inert organic solvent at elevated temperatures.
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