- Quinolinones as Inhibitors of Translation Initiation Complex
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Provided herein are compounds and pharmaceutical compositions comprising quinolinones. The quinolinones and compositions thereof are useful as eukaryotic translation initiation factor 4F (eIF4F) complex modulators.
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- PROTEIN KINASE INHIBITORS
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The present invention provides a compound incorporating a group of formula (I) wherein: 1 of X, Y and Z is nitrogen and the other 2 are carbon; V is sulpur or carbon; R3 is oxygen or fluorine; R4 is an optionally present C1-3 alkyl group optionally substituted by fluorine; R5 is an optionally present cyclic group with 5-7 heavy atoms in the ring which may be carbocyclic or heterocyclic and aromatic or aliphatic and is optionally substituted, e.g. by a halogen, C1-2 alkyl or fluoroalkyl, OH, OR6, cyano, COOR6, CONHR6, sulfonamide or NHR6, in which R6 is a C1-2 alkyl or fluoroalkyl; at least one of R4 and R5 is present and R4 and R5 may both be present; m and n are each 1 or 2 depending on the identity of V and R3; when n=2 each R3 may be the same or different but are preferably the same, when m=2, each R4 and each R5 may be the same or different but are preferably the same; and W represents hydrogen, carbon, nitrogen, oxygen or sulphur; or incorporating a salt, hydrate or solvate of a group of formula (I); as well as therapeutic uses of these compounds, in particular as inhibitors of protein kinase activity and in the treatment of inflammation, inflammatory conditions and cancer.
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- COMPOUNDS
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The present invention provides a compound incorporating a group of formula (I) wherein: 1 of X, Y and Z is nitrogen and the other 2 are carbon; R" is hydrogen, methyl, ethyl or propyl; and W represents hydrogen, carbon, nitrogen, oxygen or sulphur; or incorporating a salt, hydrate or solvate of a group of formula (I); as well as therapeutic uses of these compounds, in particular as inhibitors of protein kinase activity and in the treatment of inflammation, inflammatory conditions and cancer.
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- Synthesis of 4-aryl-1,7-naphthyridine-2(1H)-thiones by the electrocyclic reaction of 4-(1-arylalk-1-enyl)-3-isothiocyanatopyridines Generated in situ from the corresponding Isocyanides
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A convenient synthis for 4-substituted and 3,4-disubstituted 1,7-naphthyridine-2(1H)-thiones 7 has been developed. The method is based on the electrocyclic reaction of 4-(1-arylalk-1-enyl)-3-isothiocyanatopyridines 6, generated in situ by the treatment of the respective isocyanides 5 with S 8 in the presence of a catalytic amount of selenium. The isocyanides 5 can be easily prepared from commercially available pyridin-3-amine by conventional organic reactions.
- Kobayashi, Kazuhiro,Kozuki, Taketoshi,Suzuki, Teruhiko
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p. 556 - 563
(2012/05/20)
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- Design, synthesis, and structure-activity relationships of aminopyridine N-oxides, a novel scaffold for the potent and selective inhibition of p38 mitogen activated protein kinase
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A novel series of aminopyridine N-oxides were designed, synthesized, and tested for their ability to inhibit p38α MAP kinase. Some of these compounds showed a significant reduction in the LPS-induced TNFR production in human whole blood. Structure-activit
- Lumeras, Wenceslao,Caturla, Francisco,Vidal, Laura,Esteve, Cristina,Balagué, Cristina,Orellana, Adelina,Domínguez, María,Roca, Ramón,Huerta, Josep M.,Godessart, Núria,Vidal, Bernat
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experimental part
p. 5531 - 5545
(2010/02/28)
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- Synthesis of aza analogues of the anticancer agent batracylin
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Three series of pyrido-fused pyrimido[2,1-a]isoindol-7-ones were prepared from readily available (aminopyridinyl)(aryl)methanones by reduction followed by a Mitsunobu reaction with phthalimide and acid-catalysed cyclodehydration. This approach provides a wide variety of aza analogues of the antitumour agent batracylin.
- Martínez-Viturro, Carlos M.,Domínguez, Domingo
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p. 4707 - 4710
(2008/03/13)
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- QUINOLINONE DERIVATIVES AS INHIBITORS OF C-FMS KINASE
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The invention is directed to compounds of Formulae I and II: (I) (II) wherein R1, R2, R3, R5, R6, Y1, Y2, Y3, Y4 and X are set forth in the specification, as well as solvates, hydrates, tautomers or pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase.
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Page/Page column 29
(2010/02/10)
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- 2-(Dimethylaminomethyl)-tetrahydroisoxazolopyridobenzazepine derivatives. Synthesis of a new 5-HT(2C) antagonist with potential anxiolytic properties.
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Following the program started at Johnson & Johnson Pharmaceutical Research & Development searching for 5-HT(2A/2C) antagonists, we now report on the synthesis of 2-(dimethylaminomethyl)-2,3,3a,8-tetrahydroisoxazolo[3,2-a]pyrido[3,4-c]-[2]benzazepine and 2-(dimethylaminomethyl)-2,3,3a,8-tetrahydroisoxazolo[3,2-a]pyrido[3,2-c]-[2]benzazepine. A new method for the synthesis of pyridobenzazepines is described as well. The affinities for several receptors as well as the mCPP antagonistic activity of the compounds synthesised are described.
- Andres, J Ignacio,Alonso, Jose M,Fernandez, Javier,Iturrino, Laura,Martinez, Pedro,Meert, Theo F,Sipido, Victor K
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p. 3573 - 3577
(2007/10/03)
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- Preparation of 4-substituted 3-amino-2-chloropyridines, synthesis of a nevirapine analogue
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A new method for preparing 3-amino-2-chloropyridines with a substituent (methyl, phenyl, carboxamide, methoxycarbonyl, acetyl, benzoyl and cyano) at the 4-position has been developed. An isoquinoline analogue of the reverse transcriptase inhibitor Nevirapine has been synthesized from the 4-amino-3-chloroisoquinoline.
- Bakke,Riha
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- Synthesis of ortho-substituted aminopyridines. Metalation of pivaloylamino derivatives
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The three isomeric pivaloylaminopyridines were lithiated in more than 80% yields. Aminopyridine derivatives were treated by 2.5-3 equivalents of the complex BuLi-TMEDA at -10° in diethyl ether. Reaction of the lithiated species with various electrophiles afforded a number of ortho-substituted pivaloylaminopyridines in good yields. Secondary pyridine alcohols were oxidized to the corresponding aminopyridyl ketones. Pyridopyrimidines, benzonaphthyridines as well as an analogue of the natural antitumor alkaloid ellipticine has been synthesized showing the versatility of the method.
- Estel,Linard,Marsais,Godard,Queguiner
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p. 105 - 112
(2007/10/02)
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