- INHIBITORS OF MALT1 AND USES THEREOF
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Provided herein are compounds that inhibit MALTl, a protein whose activity is responsible for constitutive NF-κΒ signaling in certain cancers (e.g., activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL)). Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating MALTl -related diseases and disorders (e.g., cancer) with the compounds in a subject, by administering the compounds and/or compositions described herein.
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Paragraph 00365
(2018/09/28)
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- 4-(Trifluoromethyl)quinoline derivatives
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Under carefully controlled conditions, ethyl 4,4,4-trifluoroacetoacetate (ethyl 4,4,4-trifluoro-3-oxobutanoate) can be condensed with anilines and subsequently cyclized to give 4-trifluoromethyl-2-quinolinones 1 although only in poor yield. Heating these products with phosphoryl tribromide affords 2-bromo-4-(trifluoromethyl)quinolines 2 which can be converted into 4-(trifluoromethyl)quinolines 3 by reduction, 4-trifluoromethyl-2-quinolinecarboxylic acids 4 by permutational halogen/metal exchange followed by carboxylation, and 2-bromo-4-trifluoromethyl-3-quinolinecarboxylic acids 5 by consecutive treatment with lithium diisopropylamide and dry ice. Debromination of acids 5 makes 4-trifluoromethyl-3-quinolinecarboxylic acids 6 available. As at any time 2-trifluoromethyl-4-quinolinones 9 may form instead of the expected isomers 1, the structures have to be assigned on the basis of unequivocal NMR spectral criteria. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Lefebvre, Olivier,Marull, Marc,Schlosser, Manfred
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p. 2115 - 2121
(2007/10/03)
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- Recommendable routes to trifluoromethyl-substituted pyridine- and quinolinecarboxylic acids
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As part of a case study, rational strategies for the preparation of all ten 2-, 3-, or 4-pyridinecarboxylic acids and all nine 2-, 3-, 4-, or 8-quinolinecarboxylic acids bearing trifluoromethyl substituents at the 2-, 3-, or 4-position were elaborated. The trifluoromethyl group, if not already present in the precursor, was introduced either by the deoxygenative fluorination of suitable carboxylic acids with sulfur tetrafluoride or by the displacement of ring-bound bromine or iodine by trifluoromethylcopper generated in situ. The carboxy function was produced by treatment of organolithium or organomagnesium intermediates, products of halogen/metal or hydrogen/ metal permutation, with carbon dioxide. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).
- Cottet, Fabrice,Marull, Marc,Lefebvre, Olivier,Schlosser, Manfred
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p. 1559 - 1568
(2007/10/03)
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- The direct metalation and subsequent functionalization of trifluoromethyl-substituted pyridines and quinolines
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Depending on the choice of the reagent, 2-(trifluoromethyl)-pyridine can be selectively metalated and subsequently carboxylated of otherwise functionalized either at the 3- or at the 6-position. "Optional site selectivity" can also be achieved with 4-(trifluoromethyl)pyridine, which may be deprotonated either at the 2- or at the 3-position. In contrast, 3-(trifluoromethyl)pyridine undergoes nucleophilic addition and ensuing decomposition whatever the base. Depending on the reaction conditions, 2-(trifluoromethyl)quinoline displays reactivity toward lithium reagents at its 3-, 4-, or 8-positions, 3-(trifluoromethyl)quinolines at the 2- or 4-positions, and 4-(trifluoromethyl)quinoline at the 2- or 3-positions. It was therefore possible to prepare four trifluoromethyl-substituted pyridinecarboxylic acids (1, 4, 9, and 10) and six trifluoromethyl-substituted quinolinecarboxylic acids (11, 13, 14, 15, 17, and 18) regioisomerically uncontaminated and in a most straightforward way. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).
- Schlosser, Manfred,Marull, Marc
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p. 1569 - 1575
(2007/10/03)
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- Synthesis of some fluorinated nitrogen heterocycles from (diethylaminomethylene) hexafluoroacetylacetone (DAMFA)
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Simple and highly efficient syntheses of the title compounds from DAMFA are described in the quinoline, azepinonaphtalene, azaphenanthrene(s), pyridopyridine, pyrazole, pyrrole and pyrimidine series.
- Soufyane, Mustapha
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p. 7737 - 7740
(2007/10/02)
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