- XANTHINE DERIVATIVE INHIBITORS OF BET PROTEINS
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This invention relates to xanthine derivative compounds that are inhibitors of BET bromodomains proteins, the method of preparation thereof and applications thereof.
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Page/Page column 92
(2017/07/14)
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- Exploring Selective Inhibition of the First Bromodomain of the Human Bromodomain and Extra-terminal Domain (BET) Proteins
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A midthroughput screening follow-up program targeting the first bromodomain of the human BRD4 protein, BRD4(BD1), identified an acetylated-mimic xanthine derivative inhibitor. This compound binds with an affinity in the low micromolar range yet exerts suitable unexpected selectivity in vitro against the other members of the bromodomain and extra-terminal domain (BET) family. A structure-based program pinpointed a role of the ZA loop, paving the way for the development of potent and selective BET-BRDi probes.
- Raux, Brigitt,Voitovich, Yuliia,Derviaux, Carine,Lugari, Adrien,Rebuffet, Etienne,Milhas, Sabine,Priet, Stéphane,Roux, Thomas,Trinquet, Eric,Guillemot, Jean-Claude,Knapp, Stefan,Brunel, Jean-Michel,Fedorov, Alexey Yu.,Collette, Yves,Roche, Philippe,Betzi, Stéphane,Combes, Sébastien,Morelli, Xavier
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supporting information
p. 1634 - 1641
(2016/03/05)
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- Carboxylic acid-catalyzed one-pot synthesis of cyanoacetylureas and their cyclization to 6-aminouracils in guanidine ionic liquid
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A novel, one-pot, carboxylic acid-catalyzed synthesis of cyanoacetylureas via in situ generated ureas and their cyclization to 6-aminouracils in the presence of the guanidine-based ionic liquid 1,1,3,3-tetramethylguanidine lactate [TMG][Lac] is described. The ureas were synthesized from amines and potassium cyanate, which on reaction with cyanoacetic acid in the presence of acetic anhydride in the same pot afforded cyanoacetylureas, which undergo cyclization in [TMG][Lac] as solvent as well as catalyst to afford 6-aminouracils. One-pot synthesis of cyanoacetylureas, efficient and rapid cyclization, better yield, shorter reaction time, easy workup procedure, and recyclability of the ionic liquid are some advantages of this procedure.
- Chavan, Sunil S.,Shelke, Rupesh U.,Degani, Mariam S.
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p. 399 - 403
(2013/05/21)
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- Ionic liquid mediated one-pot synthesis of 6-aminouracils
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A novel, one-pot synthesis of 6-aminouracils via in situ generated ureas and cyanoacetylureas in the presence of an ionic liquid catalyst, 1,1,3,3-tetramethylguanidine acetate, is described. The catalyst can be recycled for five consecutive runs without loss of activity. The mechanism for the ring closure of cyanoacetylurea to 6-aminouracil is also discussed.
- Chavan, Sunil S.,Degani, Mariam S.
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supporting information; experimental part
p. 296 - 299
(2012/03/26)
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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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- Amide substituted xanthine derivatives
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The present invention is a 1,3,8 substituted xanthine derivative of formula I or a pharmaceutically acceptable salt thereof, wherein R1, R2 and R3 are as defined in the specification. Compounds of formula I and pharmaceutically acceptable salts or prodrugs thereof show activity as modulators of gluconeogenesis.
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- XANTHINE DERIVATIVES AS A2B ADENOSINE RECEPTOR ANTAGONISTS
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Disclosed are compounds that are A2B adenosine receptor antagonists, useful for treating various disease states, including asthma and diarrhea.
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- AMIDE SUBSTITUTED XANTHINE DERIVATIVES WITH GLUCONEOGENESIS MODULATING ACTIVITY
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The present invention is a 1,3,8 substituted xanthine derivative of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2 and R3 are as defined in the specification. Compounds of formula (I) and pharmaceutically acceptable salts or prodrugs thereof show activity as modulators of gluconeogenesis.
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- A2B adenosine receptor antagonists
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Disclosed are novel compounds that are A2B adenosine receptor antagonists, useful for treating various disease states, including asthma and diarrhea.
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- Di- or trisubstituted xanthines with neuroleptic properties and composition
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The invention relates to xanthines corresponding to the formula STR1 and physiologically acceptable salts thereof, in which R1 represents C2 -C4 -alkyl, C3 -C4 -isoalkyl, CH2 -(C2 -C3 -alkenyl) or CH2 -(C3 -isoalkenyl); R3 represents C3 -C5 -alkyl, C3 -C5 -isoalkyl, CH2 -(C2 -C4 -alkenyl) or CH2 -(C3 -C4 -isoalkenyl); R8 represents H, methyl or ethyl; with the proviso that (1) when R8 represents H, R1 is allyl and (2) R1 and R3 cannot both represent butyl or allyl at the same time. The compounds show non-specific or anxiolytic sedative activity.
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- Method and pharmaceutical preparation for treating chronic obstructive airway disease and cardiac disease, and intermediates for the preparation of therapeutically active xanthine derivatives
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A method for the treatment of chronic obstructive airway disease or cardiac disease, characterized by the administration of a compound of the formula STR1 wherein R is n-propyl, n-butyl or isobutyl or a therapeutically acceptable salt thereof.
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