- PHD INHIBITOR COMPOUNDS, COMPOSITIONS, AND USE
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The present invention provides, in part, novel small molecule inhibitors of PHD, having a structure according to Formula (A), and sub-formulas thereof, or a pharmaceutically acceptable salt thereof. The compounds provided herein can be useful for treatmen
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Paragraph 0449-0450
(2021/09/26)
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- SUBSTITUTED 2,4 DIAMINO-QUINOLINE AS NEW MEDICAMENT FOR FIBROSIS, AUTOPHAGY AND CATHEPSINS B (CTSB), L (CTSL) AND D (CTSD) RELATED DISEASES
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The present invention relates to novel 2-primary amino-4-secondary amino-quinoline derivatives, their manufacture, pharmaceutical compositions comprising them and their use as medicaments. The active compounds of the present invention can be useful as a medicament in the treatment and/or the decreasing and/or the prevention of fibrosis and/or fibrosis related diseases, or for use as a medicament in the treatment and/or the decreasing and/or the prevention of the autophagy and/or autophagy related diseases and for the inhibition of the autophagy flux, or for use in the inhibition of cathepsins B (CTSB), L (CTSL) and/or D (CTSD) and/or cathepsins B (CTSB), L (CTSL) and/or D (CTSD) related diseases; with the proviso that said compounds are not to be used for the treatment of any forms of cancers.
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Paragraph 1532; 1533
(2020/03/26)
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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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Paragraph 1575
(2015/09/22)
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- CHEMICAL COMPOUNDS
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The invention relates to sulfonamide derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to a new sulfonamide Nav1.7 inhibitors of formula (I): or a pharmaceutically acceptable salt thereof, wherein X, Ar1, R1, R2, R3, R4 and R5 are as defined in the description. Nav 1.7 inhibitors are potentially useful in the treatment of a wide range of disorders, particularly pain.
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Page/Page column 93-94
(2012/02/02)
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- TGR5 AGONISTS
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TGR5 agonists of structural formula VIII(Q), wherein X, R1, R2, and R5 are defined in the specification, pharmaceutically acceptable salts thereof, compositions thereof, and use of the compounds and compositions for treating diseases. The invention also comprises use of the compounds in and for the manufacture of medicaments, particularly for treating diseases.
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Page/Page column 145-146
(2011/06/26)
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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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- TRIAZOLE AND IMIDAZOLE DERIVATIVES FOR USE AS TGR5 AGONISTS IN THE TREATMENT OF DIABETES AND OBESITY
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The present invention comprises TGR5 agonists of structural formula I, wherein X, R1, R2, and R5 are defined herein, as well as N-oxides of them and pharmaceutically acceptable salts thereof. The invention further comprise
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Page/Page column 136-137
(2012/01/30)
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- Synthesis and structure-activity relationships of N-aryl(indol-3-yl)glyoxamides as antitumor agents
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The synthesis and study of the structure-activity relationships of cytotoxic compounds based on N-pyridinyl or N-aryl-2-(1-benzylindol-3-yl)glyoxamide skeleton, represented by the lead structures D-24241 and D-24851, are described. The presence of N-(pyridin-4-yl) moiety was crucial for activity and 2-[1-(4-chloro-3-nitrobenzyl)-1H-indol-3-yl]-2-oxo-N-(pyridin-4-yl)aceta mide (55), the most potent derivative, showed IC50 = 39 nM, 51 nM and 11 nM against HeLa/KB (human cervix carcinoma), L1210 (murine leukemia) and SKOV3 (human ovarian carcinoma) cell lines proliferation assay, respectively, as active as the lead compounds.
- Marchand, Pascal,Antoine, Maud,Baut, Guillaume Le,Czech, Michael,Baasner, Silke,Guenther, Eckhard
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experimental part
p. 6715 - 6727
(2009/12/06)
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- Substituted Diphenylethers, -Amines, -Sulfides and -Methanes for the Treatment of Respiratory Disease
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The invention relates to substituted diphenylethers, -amines, -sulfides, and -methanes as useful pharmaceutical compounds for treating respiratory-disorders, pharmaceutical compositions containing them, and processes for their preparation.
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Page/Page column 22
(2009/01/20)
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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 91
(2008/06/13)
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- NOVEL COMPOUNDS
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The invention relates to substituted phenylacetic acids as useful pharmaceutical compounds for treating respiratory disorders, pharmaceutical compositions containing them, and processes for their preparation.
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Page/Page column 28
(2008/06/13)
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- Indole derivatives as MCP-1 receptor antagonists
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A compound of Formula I, wherein: R1 is hydrogen, halo, methyl, ethyl or methoxy; R2 is hydrogen, halo, methyl, ethyl or methoxy; R3 is a halo group, lower alkyl, lower alkenyl, lower alkynyl, alkoxy, trifluoromethyl, nitro, cyano, trifluoromethoxy, C(O)R7, or S(O)nR7 where n is 0, 1 or 2 and R7 is an alkyl group; R4 is a halo, trifluoromethyl, methylthio, methoxy, trifluoromethoxy or lower alkyl, lower alkenyl or lower alkynyl or COR8 where R8 is lower alkyl; R6 is hydrogen, halo, lower alkyl, lower alkenyl, lower alkynyl or COR9 where R9 is lower alkyl; provided that when R1 is hydrogen, halo or methoxy, R2 is hydrogen, halo, methyl, ethyl or methoxy, R5 and R6 are both hydrogen, and one of R3 or R4 is not halo or trifluoromethyl; or a pharmaceutically acceptable salt or prodrug thereof. These compounds have useful activity for the treatment of inflammatory disease, specifically in antagonizing an MCP-1 mediated effect in a warm-blooded animal such as a human being.
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- Non-nucleoside reverse transcriptase inhibitors
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The present invention provides compounds for treating or preventing an HIV infection, or treating AIDS or ARC comprising administering a compound according to formula I where Ar, R1-R5, R7a, R7b, R7c, R8-R10, X1, X2 m, n, o and p are as defined herein.
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Page/Page column 27
(2008/06/13)
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- LIGANDS OF MELANOCORTIN RECEPTORS AND COMPOSITIONS AND METHODS RELATED THERETO
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Compounds which function as melanocortin receptor ligands and having utility in the treatment of melanocortin receptor-based disorders. The compounds have the following structure (I): (I) including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein m, n, q, s, R1, R1a, R1b, R2, R3, R4a, R4b, R5a, R5b, X1, X2, X3, X4 and Ar are as defined herein. Pharmaceutical compositions containing a compound of structure (I), as well as methods relating to the use thereof, are also disclosed.
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Page/Page column 95
(2010/02/11)
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- Non-nucleoside reverse transcriptase inhibitors
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This invention relates to novel heterocyclic compounds of formula I wherein R1—R4, X1 and X2 are as defined in the summary and pharmaceutically acceptable salts and solvates thereof, methods to inhibit or modula
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- Non-nucleoside reverse transcriptase inhibitors
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This invention relates to novel pyridazinone derivatives of formula I wherein R1-R4, R7, R8 and X1 are as defined in the summary and pharmaceutically acceptable salts and solvates thereof, methods to inhibit or modulate Human Immunodeficiency Virus (HIV) reverse transcriptase with compounds of formula I, pharmaceutical compositions containing of formula I admixed with at least one solvent, carrier or excipient and processes to prepare compounds of formula I. The compounds are useful for treating disorders in which HIV and genetically related viruses are implicated
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Page/Page column 60
(2010/02/08)
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- Anthranilic acid derivatives as inhibitors of the cGMP-phosphodiesterase
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Compounds of formula (I) STR1where R 1 is hydrogen; R 2 is nitro, cyano or halo(lower)alkyl; R 3 is phenyl substituted with one or more substituents selected from halogen, cyano and lower alkoxy; A is a lower alkylene group; R 4 is a group CR 6 R 7 R 8 wherein R 6 and R 7 form, together with the carbon atom to which they are attached a cycloalkyl group optionally substituted with hydroxy, lower alkoxy or a lower alkanoylamino; and R 8 is hydrogen; its prodrug and a salt thereof.
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- Synthesis and antirhinovirus activity of 6-(dimethylamino)-2-(trifluoromethyl)-9-(substituted benzyl)-9H-purines
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A series of 6-(dimethylamino)-2-(trifluoromethyl)-9-(substituted benzyl)purines was synthesized and tested for antirhinovirus activity. Most of the compounds were synthesized by alkylation of 6-chloro-2-(trifluoromethyl)-9H-purine with the appropriate benzyl halide followed by displacement of the chloro group with dimethylamine. Alternatively, 6-(dimethylamino)-2-(trifluoromethyl)purine was alkylated with the appropriate benzyl halide. Although several different aryl substituents provided compounds with IC50's = 0.03 μM against rhinovirus serotype 1B, no congener was significantly more active than the parent 2. Twenty-three compounds were tested against 18 other serotypes, but none exhibited a uniform profile of activity.
- Kelley,Linn,Selway
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p. 1757 - 1763
(2007/10/02)
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- Synthesis and Dopaminergic Activity of Some Halogenated Mono- and Dihydroxylated 2-Aminotetralins
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In a series of 7,8-dihydroxy-1-phenyltetrahydro-3-benzazepine dopamine receptor agonists introduction of a chloro or fluoro substituent into the 6-position increases dopaminergic potency.Also, in this series replacement of the 7-hydroxyl group with a halogen results in inversion of activity from dopamine receptor agonist to antagonist.The present study was aimed at exploring the possibility that the structure-activity observations in the 3-benzazepine series of dopaminergic agents might be extrapolated to another class of dopamine receptor agonists, the 2-aminotetralins.Thus, a series of chloro- and fluoro-substituted mono- and dihydroxylated 2-aminotetralins was prepared and evaluated for dopaminergic properties in D-1 and D-2 receptor-related tests.Introduction of a chloro substituent into the 8-position of the prototype of this series, i.e. 2-amino-6,7-dihydroxytetralin (ADTN), resulted in a compound with a high degree of selectivity for the D-1 subpopulation of dopamine receptors; it was equally or more potent than ADTN in the D-1 receptor-related tests with greatly decreased effectiveness in the tests involving D-2 receptors.A similar effect was observed with 8-fluoro-ADTN; however, the N-(4-hydroxyphenethyl)-N-propyl derivative 4g of the 8-chloro-substituted ADTN showed markered D-2 binding affinity.Conversely, introduction of a chloro substituent into the 5-position of ADTN markedly decreased D-1 receptor affinity and efficacy.This effect was not seen with the related 5-fluoro derivative, suggesting D-1 receptors are more sensitive to bulk in the 5-position of ADTN than are the D-2 receptors.Replacement of either the 6- or 7-hydroxyl groups of ADTN with a chloro or fluoro substituent, in contrast, did not parallel the response seen in the benzazepine series (i.e., the compounds uniformly demonstrated less receptor affinity and did not have dopamine receptor antagonist activity); however, the decrease in agonist potency was less marked in the case of 2-amino-6-fluoro-7-hydroxytetralins than in the chlorinated monohydroxyaminotetralins.Thus, a parallelism in structure-activity relationships in the benzazepine and aminotetralin series of dopamine receptor agonists was not observed.The differences may reflect altered modes of receptor binding in the two series.
- Weinstock, Joseph,Gaitanopoulos, Dimitri E.,Oh, Hye-Ja,Pfeiffer, Francis R.,Karash, Carole B.,et al.
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p. 1615 - 1627
(2007/10/02)
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