- SUBSTITUTED XANTHINE DERIVATIVES
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The present invention relates to compounds of formula (I) a process for their manufacture, pharmaceutical compositions containing them and their use in therapy, particularly in the treatment of conditions having an association with TRPC5 containing ion ch
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Page/Page column 23
(2020/07/07)
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- SUBSTITUTED XANTHINE DERIVATIVES
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The present invention relates to compounds of formula (I) a process for their manufacture, pharmaceutical compositions containing them and their use in therapy, particularly in the treatment of conditions having an association with TRPC5 containing ion channels. R1, R2, R3, R4 and R5 have meanings given in the description.
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Page/Page column 36
(2020/07/07)
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- NOVEL SUBSTITUTED XANTHINE DERIVATIVES
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The present invention relates to substituted xanthine derivatives, pharmaceutical compositions containing them and their use in therapy, particularly in the treatment of conditions having an association with TRPC5 containing ion channels.
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Page/Page column 26
(2019/01/30)
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- CAFFEINE INHIBITORS OF MTHFD2 AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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- Imidazopyridine- and purine-thioacetamide derivatives: Potent inhibitors of nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1)
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Nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) belongs to the family of ecto-nucleotidases, which control extracellular nucleotide, nucleoside, and (di)phosphate levels. To study the (patho)physiological roles of NPP1 potent and selective inhibitors with drug-like properties are required. Therefore, a compound library was screened for NPP1 inhibitors using a colorimetric assay with p-nitrophenyl 5′-thymidine monophosphate (p-Nph-5′-TMP) as an artificial substrate. This led to the discovery of 2-(3H-imidazo[4,5-b]pyridin-2-ylthio)-N-(3,4-dimethoxyphenyl)acetamide (5a) as a hit compound with a Ki value of 217 nM. Subsequent structure-activity relationship studies led to the development of purine and imidazo[4,5-b]pyridine analogues with high inhibitory potency (Ki values of 5.00 nM and 29.6 nM, respectively) when assayed with p-Nph-5′-TMP as a substrate. Surprisingly, the compounds were significantly less potent when tested versus ATP as a substrate, with Ki values in the low micromolar range. A prototypic inhibitor was investigated for its mechanism of inhibition and found to be competitive versus both substrates.
- Chang, Lei,Lee, Sang-Yong,Leonczak, Piotr,Rozenski, Jef,De Jonghe, Steven,Hanck, Theodor,Müller, Christa E.,Herdewijn, Piet
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p. 10080 - 10100
(2015/02/05)
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- Selective, high affinity A2B adenosine receptor antagonists: N-1 monosubstituted 8-(pyrazol-4-yl)xanthines
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A series of N-1 monosubstituted 8-pyrazolyl xanthines have been synthesized and evaluated for their affinity for the adenosine receptors (AdoRs). We have discovered two compounds 18 (CVT-7124) and 28 (CVT-6694) that display good affinity for the A2B AdoR (Ki = 6 nM and 7 nM, respectively) and greater selectivity for the human A1, A2A, and A3 AdoRs (>1000-, >830-, and >1500-fold; >850-, >700-, and >1280-fold, respectively). CVT-6694 has been shown to block the release of interleukin-6 and monocyte chemotactic protein-1 from bronchial smooth muscle cells (BSMC), a process believed to be promoted by activation of A2B AdoR.
- Kalla, Rao V.,Elzein, Elfatih,Perry, Thao,Li, Xiaofen,Gimbel, Art,Yang, Ming,Zeng, Dewan,Zablocki, Jeff
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p. 1397 - 1401
(2008/09/21)
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- METHOD OF PREVENTING AND TREATING HEPATIC DISEASE USING A2B ADENOSINE RECEPTOR ANTAGONISTS
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The invention is related to methods of preventing and treating hepatic fibrosis using A2B adenosine receptor antagonists and utility in the treatment and prevention of liver damage caused by alcohol abuse, surgical intervention, viral hepatitis, the ingestion of hepatotoxic drugs, or other hepatic diseases. The invention also relates to pharmaceutical compositions for use in the method.
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Page/Page column 22
(2010/11/28)
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- Method of wound healing using A2B adenosine receptor antagonists
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The present invention relates to methods of wound healing using A2B adenosine receptor antagonists. The invention also relates to methods for the preparation of such compounds, and to pharmaceutical compositions containing them.
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Page/Page column 22
(2008/06/13)
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- METHOD OF PREVENTING AND TREATING AIRWAY REMODELING AND PULMONARY INFLAMMATION USING A2B ADENOSINE RECEPTOR ANTAGONISTS
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The present invention relates to methods of preventing airway remodeling using A2B adenosine receptor antagonists. This invention finds utility in the treatment and prevention of asthma, COPD, pulmonary fibrosis, emphysema, and other pulmonary diseases. The invention also relates to pharmaceutical compositions for use in the method.
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Page/Page column 67
(2010/11/08)
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- A2B adenosine receptor antagonists
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Disclosed are processes for the synthesis of novel compounds that are A2B adenosine receptor antagonists, useful for treating various disease states, including asthma and diarrhea.
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- 3,8-Dialkylxanthines
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The invention refers to compounds having activity against chronic obstructive airway disease or cardiovascular disease, characterized by the formula STR1 wherein R1 is ethyl, n-propyl, n-butyl, isobutyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexylmethyl, and R2 is methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, tert. butyl, or cyclobutyl provided that R1 is ethyl when R2 is methyl, or a physiologically acceptable salt thereof. The invention also refers to processes for the preparation of these compounds, a pharmaceutical preparation containing one of the compounds and a method for the treatment of chronic obstructive airway disease and cardiovascular disease.
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- Method for the treatment of chronic obstructive airway or cardiac diseases
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A method for the treatment of chronic obstructive airway disease or cardiac disease by administration 3-ethylxantine or a pharmaceutically acceptable salt thereof; a pharmaceutical preparation containing 3-ethylxanthine.
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