- Photocatalytic C-H Amination of Aromatics Overcoming Redox Potential Limitations
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We report the photocatalytic C-H amination of aromatics overcoming redox potential limitations. Radical cations of aromatic compounds are generated photocatalytically using Ru(phen)3(PF6)2, which has a reduction potential at a high oxidation state (Ered(RuIII/RuII) = +1.37 V vs SCE) lower than the oxidation potentials of aromatic substrates (Eox = +1.65 to +2.27 V vs SCE). The radical cations are trapped with pyridine to give N-arylpyridinium ions, which were converted to aromatic amines.
- Ikarashi, Gun,Kano, Naokazu,Morofuji, Tatsuya
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supporting information
p. 2822 - 2827
(2020/04/16)
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- Weak Links to Differentiate Weak Bonds: Size-Selective Response of π-Conjugated Macrocycle Gels to Ammonium Ions
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Molecular-level host-guest interactions can drive gel-to-sol phase transitions of the bulk material. Using supramolecular gels constructed from π-conjugated aza-crown macrocycles, we have investigated the effects of guest chemical structures on the kinetics of gel disassembly. While ammonium ions bind only weakly to the individual macrocycles in solution, gel-to-sol transitions of self-assembled macrocycles occur readily under ambient conditions. This net signal amplification process was monitored conveniently by time-dependent spectroscopic studies to reveal a straightforward correlation between the response rate and shape/size of the guest species. Well-designed weak links thus respond to subtle differences in weak bonds and translate them into visually discernible macroscopic signaling events.
- Kang, Suk-Il,Lee, Milim,Lee, Dongwhan
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supporting information
p. 5980 - 5986
(2019/04/26)
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- Direct and practical synthesis of primary anilines through iron-catalyzed C-H bond amination
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The direct C-H amination of arenes is an important strategy to streamline the discovery and preparation of functional molecules. Herein, we report an operationally simple arene C-H amination reaction that, in contrast to most literature precedent, affords directly the synthetically versatile primary aniline products without relying on protecting group manipulations. Inexpensive Fe(II)-sulfate serves as a convenient catalyst for the transformation. The reaction tolerates a wide scope of arenes, including structurally complex drugs. Importantly, the arene substrates are used as limiting reagents in the transformation. This operationally simple transformation should considerably accelerate the discovery of medicines and functional molecules.
- Legnani, Luca,Cerai, Gabriele Prina,Morandi, Bill
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p. 8162 - 8165
(2018/05/22)
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- TUBULIN BINDING AGENTS
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The invention provides combretastatin A-4 like compounds that are modified to have enhanced tubulin binding activity and in some embodiments the ability to promote accumulation in the vasculature undergoing angiogenesis (homing activity). The compounds are based on the combretastatin A-4 skeletal structure having a tubulin-binding pharmacophore comprising two fused rings (A and B rings) in which the B ring is substituted with (a) an aromatic ring structure (C ring) and (b) a second substituent/functional group that comes off the B ring. The aromatic ring structure is typically a six membered ring phenolic or aniline structure, or may also be a fused ring structure such as a substituted or unsubstituted naphthalene. The second substituent on the B ring may for example be a substituent which has been found to provide enhanced tubulin binding activity (for example a carbonyl group), or may be a substituent that facilitates functionalisation of the B ring (for example an hydroxyl or amine group), or it may be a binding agent for a target that is preferentially expressed on vasculature undergoing angiogenesis, and not expressed on quiescent vasculature.
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Paragraph 0632; 0633; 0634; 0635; 0636; 0637; 0638
(2015/02/18)
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- 7-HYDROXY-INDOLINYL ANTAGONISTS OF P2Y1 RECEPTOR
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The present invention provides compounds of Formula (I): Formula (I) as defined in the specification and compositions comprising any of such novel compounds. These compounds are antagonists of P2Y1 receptor which may be used medicaments.
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Paragraph 00169
(2014/02/16)
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- Synthesis and biological evaluation of enantiomerically pure cyclopropyl analogues of combretastatin A4
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To evaluate the influence of stereochemistry on biological activities of cis-cyclopropyl combretastatin A4 (CA4) analogues, we have prepared several cyclopropyl compounds in their pure enantiomeric forms. The key reactions in our synthesis are the cyclopropanation of a (Z)-alkenylboron compound bearing a chiral auxiliary, and the cross-coupling of both enantiomeric cyclopropyl trifluoroborate salts with aryl and olefinic halides. Three pairs of cis-cyclopropyl CA4 analogues were evaluated for their potential antivascular activities. The diarylcyclopropyl compounds with SR-configuration (-)-1b, (-)-2b and the cyclopropylvinyl enantiomer (+)-3a with RR-configuration were the most potent tubulin polymerization inhibitors. A correlation was noted between anti-tubulin activity and rounding up activity of endothelial cells. The cytotoxic activity on B16 melanoma cells was in the submicromolar range for most compounds, but unlike the anti-tubulin activity, there was no difference in cytotoxic activity between racemic and enantiomerically pure forms for the three series of compounds. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized cis-cyclopropyl CA4 analogues for potential antivascular activities.
- Ty, Nancy,Pontikis, Renée,Chabot, Guy G.,Devillers, Emmanuelle,Quentin, Lionel,Bourg, Stéphane,Florent, Jean-Claude
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p. 1357 - 1366
(2013/03/29)
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- 2-Pyrimidinyl Pyrazolopyridine ErbB Kinase Inhibitors
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The present invention provides 2-pyrimidinyl pyrazolopyridine compounds, compositions containing the same, as well as processes for the preparation and their use as pharmaceutical agents.
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Page/Page column 68
(2009/06/27)
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- 2-Pyrimidinyl Pyrazolopyridine Erbb Kinase Inhibitors
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The present invention provides 2-pyrimidinyl pyrazolopyridine compounds, compositions containing the same, as well as processes for the preparation and their use as pharmaceutical agents.
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Page/Page column 93; 124
(2008/06/13)
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- N-Phenyloxamide derivatives
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A compound represented by the following general formula (I) or a salt thereof, or a hydrate thereof or a solvate thereof having an inhibitory action against plasminogen activator inhibitor-1 (PAI-1): wherein R1 represents a C6-10 aryl group; or a C6-10 aryl group substituted with a group or groups selected from the group consisting of a halogen atom, cyano group, nitro group, a C1-6 alkyl group, a halogenated C1-6 alkyl group, a C1-6 alkoxy group, a halogenated C1-6 alkoxy group and a C1-6 alkylsulfanyl group, R2 represents a C6-10 aryl group; or a C6-10 aryl group substituted with a group or groups selected from the group consisting of a halogen atom, hydroxy group, a C1-6 alkyl group, a halogenated C1-6 alkyl group, a C1-6 alkoxy group, a halogenated C1-6 alkoxy group, a C1-6 alkylsulfanyl group and phenyl group, X represents a single bond or oxygen atom, Z represents a phenylene group or a substituted phenylene group, m represents 0 or 1.
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Page/Page column 71
(2008/12/08)
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- Substituted benzazoles and methods of their use as inhibitors of Raf kinase
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New substituted benz-azole compounds, compositions and methods of inhibition of Raf kinase activity in a human or animal subject are provided. The new compounds compositions may be used either alone or in combination with at least one additional agent for the treatment of a Raf kinase mediated disorder, such as cancer.
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- Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators or caspases and inducers of apoptosis and the use thereof
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The present invention is directed to substituted 2-aryl-4-arylaminopyrimidine and analogs thereof, represented by the general Formula I: wherein A, Ar1, Ar2, R1 and R3 are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. The compounds of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
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- Benzothiazole derivatives with activity as adenosine receptor ligands
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The present invention relates to substituted benzothiazole derivitives and to their pharmaceutically acceptable salts useful for the treatment of diseases related to the adenosine receptor.
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- Substituted azabicyclic compounds
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This invention is directed to certain physiologically active compounds of formula (I) wherein represents a bicyclic ring system, of about 10 to about 13 ring members, in which the ring is an azaheterocycle, and the ring represents an azaheteroaryl ring, or an optionally halo substituted benzene ring; and N-oxides thereof, and their prodrugs, and pharmaceutically acceptable salts and solvates of the compounds of formula (I) and N-oxides thereof, and their prodrugs. Such compounds inhibit the production or physiological effects of TNF and inhibit cyclic AMP phosphodiesterase. The invention is also directed to pharmaceutical compositions comprising compounds of formula (I), their pharmaceutical use and methods for their preparation.
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- Hypervalent iodine-induced nucleophilic substitution of para-substituted phenol ethers. Generation of cation radicals as reactive intermediates
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A novel hypervalent iodine induced nucleophilic substitution of para-substituted phenol ethers in the presence of a variety of nucleophiles is described. UV and ESR spectroscopic studies indicate that this reaction proceeds via cation radicals, [ArH?+], as reactive intermediates generated by single-electron transfer (SET) from a charge-transfer (CT) complex of phenol ethers with phenyliodine(III) bis(trifluoroacetate) (PIFA). This is the first case that involves a radical intermediate on hypervalent iodine oxidations of aromatic compounds.
- Kita, Yasuyuki,Tohma, Hirofumi,Hatanaka, Kenji,Takada, Takeshi,Fujita, Shigekazu,Mitoh, Shizue,Sakurai, Hiromu,Oka, Shigenori
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p. 3684 - 3691
(2007/10/02)
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