- Enantioselective Intramolecular Copper-Catalyzed Borylacylation
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An enantioselective copper-catalyzed intramolecular borylacylation is reported. The reaction proceeds through an initial enantioselective borylcupration of the styrene, followed by a nucleophilic attack on the tethered carbamoyl chloride. The products, chiral borylated 3,3-disubstituted oxindoles, were generated in excellent yields and enantioselectivities. The versatile carbon–boron bond provides a platform for a wide array of diversification.
- Whyte, Andrew,Burton, Katherine I.,Zhang, Jingli,Lautens, Mark
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supporting information
p. 13927 - 13930
(2018/10/02)
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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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- Palladium-catalyzed direct addition of arylboronic acids to 2-aminobenzonitrile derivatives: Synthesis, biological evaluation and in silico analysis of 2-aminobenzophenones, 7-benzoyl-2-oxoindolines, and 7-benzoylindoles
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A palladium-catalyzed direct addition of arylboronic acids to unprotected 2-aminobenzonitriles has been developed, leading to a wide range of 2-aminobenzophenones with moderate to excellent yields. The transformation has broad scope and high functional group tolerance. Moreover, 2-oxoindoline-7-carbonitrile and indole-7-carbonitrile were applicable to this process for the construction of 7-benzoyl-2-oxoindolines and 7-benzoylindoles, respectively. Among the compounds examined, compound 4e possessed the most potent anticancer activity against H446 and HGC-27 in vitro, with IC50 values of 0.02 μmol L-1 and 0.09 μmol L-1, respectively, while compound 4a showed the best potent anticancer activity against SGC-7901 with an IC50 value of 0.01 μmol L-1. Furthermore, we also performed in silico molecular docking calculations to investigate the interaction mode and binding affinity between the examined compounds and their tubulin target. This journal is
- Chen, Jiuxi,Ye, Leping,Su, Weike
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supporting information
p. 8204 - 8211
(2015/01/08)
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- Palladium-catalyzed direct addition of 2-Aminobenzonitriles to sodium arylsulfinates: Synthesis of o-Aminobenzophenones
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The first example of the palladium-catalyzed synthesis of o-Aminobenzophenones in moderate to excellent yields via a direct addition of sodium arylsulfinates to unprotected 2-Aminobenzonitriles was reported. A plausible mechanism for the formation of o-Aminobenzophenones involving desulfination and addition reactions was proposed. The utility of this transformation was demonstrated by its compatibility with a wide range of functional groups. Thus, the method represents a convenient and practical strategy for synthesis of o-Aminobenzophenones.
- Chen, Jiuxi,Li, Jianjun,Su, Weike
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p. 6439 - 6449
(2014/06/10)
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- Novel access to 1,4-benzodiazepin-2-ones via the Buchwald reaction and application to the synthesis of novel heterocyclics
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A new two step strategy for the preparation of 1,4-benzodiazepin-2-ones has been developed starting from the 2-halogenobenzophenone under Buchwald conditions (Pd(OAc)2, XantPhos, Cs2CO3, dioxane 100 °C). This strategy has
- Salomé, Christophe,Schmitt, Martine,Bourguignon, Jean-Jacques
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scheme or table
p. 1033 - 1035
(2012/03/26)
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- Potent and selective inhibitors of Helicobacter pylori glutamate racemase (MurI): Pyridodiazepine amines
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An SAR study of an HTS screening hit generated a series of pyridodiazepine amines as potent inhibitors of Helicobacter pylori glutamate racemase (MurI) showing highly selective anti-H. pylori activity, marked improved solubility, and reduced plasma protei
- Geng, Bolin,Basarab, Gregory,Comita-Prevoir, Janelle,Gowravaram, Madhusudhan,Hill, Pamela,Kiely, Andrew,Loch, James,MacPherson, Lawrence,Morningstar, Marshall,Mullen, George,Osimboni, Ekundayo,Satz, Alexander,Eyermann, Charles,Lundqvist, Tomas
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scheme or table
p. 930 - 936
(2009/09/06)
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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 28
(2010/02/10)
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- Synthesis and structure-activity relationship studies on a novel series of naphthylidinoylureas as inhibitors of acyl-CoA:cholesterol O-acyltransferase (ACAT)
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The synthesis and structure-activity relationships of N-phenyl-N′-[3- (4-phenylnaphthylidinoyl)]urea derivatives 3 as a novel structural class of potent ACAT inhibitors is described. A 3-methoxy group substituted on the naphthylidinone 4-phenyl ring, toge
- Ohnuma, Satoshi,Muraoka, Masami,Ioriya, Katsuhisa,Ohashi, Naohito
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p. 1309 - 1311
(2007/10/03)
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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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- Improved Synthesis of 2,3-Disubstituted Pyridines by Metallation of 2-Chloropyridine: a Convenient Route to Fused Polyheterocycles
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Chemoselective directed metallation of 2-chloropyridine allows the synthesis of 2-substituted 3-carbonylated pyridines, advantage being taken of the metallation ortho-directing effect of the halogen, as well as its reactivity towards nucleophiles.Thus (2-chloro-, 2-methoxy-, and 2-amino-3-pyridyl)-ethanones and -arylmethanones as well as carbaldehydes have been prepared.Some of these ortho-disubstituted intermediates have been readily cyclized to fused polyheterocycles such as naphthiridines and aza-analoges of coumarins, xanthones, and acridones.
- Trecourt, Francois,Marsais, Francis,Guengoer, Timur,Queguiner, Guy
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p. 2409 - 2415
(2007/10/02)
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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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- METALLATION REGIOSELECTIVE EN SERIE PYRIDINIQUE: SYNTHESE ORIGINALE D'AMINO-2-AROYL 3-PYRIDINES
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Lithium diisopropylamide reacts with 2-fluoropyridine at low temperature: regioselectivity is excellent and metallation occurs without side reactions such as nucleophilic attack. 2-Fluoro-3-lithiopyridine is formed and with aldehydes it gives the correspo
- Guengoer, Timur,Marsais, Francis,Queguiner, Guy
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p. 139 - 150
(2007/10/02)
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