- Gas-liquid flow hydrogenation of nitroarenes: Efficient access to a pharmaceutically relevant pyrrolobenzo[1,4]diazepine scaffold
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Using a Tube-in-Tube device based on the amorphous Teflon AF-2400 fluoropolymer, a series of nitroarenes was hydrogenated to afford the corresponding aniline compounds. The system was then applied to the construction of a pyrrolobenzo[1,4]diazapene scaffold through a tandem hydrogenation-condensation-hydrogenation sequence.
- Dimitriou, Eleni,Jones, Richard H.,Pritchard, Robin G.,Miller, Gavin J.,O'Brien, Matthew
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p. 6795 - 6803
(2018/10/15)
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- A normal pressure catalytic synthesis of aniline compounds and the use of catalyst (by machine translation)
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A normal pressure catalytic synthesis of aniline compounds is the nitrobenzene compound and solvent after mixing, adding catalyst to form suspension, then transfer to the with a quartz window in the high-pressure reactor, reactor for sealing and hydrogen purge after washing, maintaining a hydrogen under normal pressure conditions, under stirring condition, heating the reaction system to10-50oC, in strength is0.01-5W/cm2under the illumination of the reaction, the reaction time is 5 - 180min. This invention has mild condition, environmental protection, low cost, simple operation, reaction period is short, high product yield, selectivity is good. (by machine translation)
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Paragraph 0075-0078
(2017/04/14)
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- Metabolically stable dibenzo[ b, e ]oxepin-11(6 H)-ones as highly selective p38 MAP kinase inhibitors: Optimizing anti-cytokine activity in human whole blood
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Five series of metabolically stable disubstituted dibenzo[b,e]oxepin-11(6H) -ones were synthesized and tested in a p38α enzyme assay for their inhibition of tumor necrosis factor-α (TNF-α) release in human whole blood. Compared to the monosubstituted dibenzo[b,e]oxepin-11(6H)-one derivatives, it has been shown that the additional introduction of hydrophilic residues at position 9 leads to a substantial improvement of the inhibitory potency and metabolic stability. Using protein X-ray crystallography, the binding mode of the disubstituted dibenzoxepinones and the induction of a glyince flip in the hinge region were confirmed. The most potent compound of this series, 32e, shows an outstanding biological activity on isolated p38α, with an IC50 value of 1.6 nM, extraordinary selectivity (by a factor >1000, Kinase WholePanelProfiler), and low ATP competitiveness. The ability to inhibit the release of TNF-α from human whole blood was optimized down to an IC50 value of 125 nM. With the promising dibenzoxepinone inhibitor 3i, a pharmacokinetic study in mice was conducted.
- Baur, Benjamin,Storch, Kirsten,Martz, Kathrin E.,Goettert, Marcia I.,Richters, André,Rauh, Daniel,Laufer, Stefan A.
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p. 8561 - 8578
(2013/12/04)
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- NOVEL PYRAZOLONE-DERIVATIVES AND THEIR USE AS PD4 INHIBITORS
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The compounds of formula (1) wherein R1 represents a phenyl derivative of formulae (a), (b) or (c) R10 is 1-3C-alkyl and R11 is 1-3C-alkyl, or R10 and R11 together with the carbon atom, to which they are bonded, form a spiro-linked 3-, 4-, 5- or 6-membered hydrocarbon ring, A is C(O) or S(O)2, and R12 is phenyl, naphthalenyl, pyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl, 1,6-naphthyridinyl, 1,8-naphthyridinyl, indolyl, phenyl substituted by R13, R14, R15 and R16, pyridinyl substituted by R17 and R18, naphthalenyl substituted by R19 and R20, quinolinyl substituted by R21 or indolyl substituted by R22, are novel effective inhibitors of the type 4 phosphodiesterase.
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Page/Page column 108
(2010/06/15)
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- FUSED HETEROCYCLIC COMPOUND
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The present invention provides a fused heterocyclic compound having a tyrosine kinase inhibitory action, which is represented by the formula: wherein R1 is a hydrogen atom, a halogen atom, or an optionally substituted group bonded via a carbon atom, a nitrogen atom or an oxygen atom; R2 is a hydrogen atom, or an optionally substituted group bonded via a carbon atom or a sulfur atom, or R1 and R2, or R2 and R3 are optionally bonded to each other to form an optionally substituted ring structure; R3 is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3 is optionally bonded to the carbon atom on ring A to form an optionally substituted ring structure; ring A is an optionally substituted benzene ring; and ring B is (i) an optionally substituted fused ring, or (ii) a pyridine ring having optionally substituted carbamoyl (the pyridine ring is optionally further substituted).
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Page/Page column 67
(2009/10/01)
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- Dihydroxylphenyl amides as inhibitors of the Hsp90 molecular chaperone
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Information from X-ray crystal structures were used to optimize the potency of a HTS hit in a Hsp90 competitive binding assay. A class of novel and potent small molecule Hsp90 inhibitors were thereby identified. Enantio-pure compounds 31 and 33 were potent in PGA-based competitive binding assay and inhibited proliferation of various human cancer cell lines in vitro, with IC50 values averaging 20 nM.
- Kung, Pei-Pei,Funk, Lee,Meng, Jerry,Collins, Michael,Zhou, Joe Zhongxiang,Catherine Johnson,Ekker, Anne,Wang, Jeff,Mehta, Pramod,Yin, Min-Jean,Rodgers, Caroline,Davies II, Jay F.,Bayman, Eileen,Smeal, Tod,Maegley, Karen A.,Gehring, Michael R.
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supporting information; experimental part
p. 6273 - 6278
(2009/08/15)
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- AMIDE RESORCINOL COMPOUNDS
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The present invention is directed to compounds of formula (I), and pharmaceutically acceptable salts and solvates thereof, their synthesis, and their use as HSP-90 inhibitors.
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- HIV protease inhibitors
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HIV protease inhibitors, obtainable by chemical synthesis, inhibit or block the biological activity of the HIV protease enzyme, causing the replication of the HIV virus to terminate. These compounds, as well as pharmaceutical compositions that contain these compounds and optionally other anti-viral agents as active ingredients, are suitable for treating patients or hosts infected with the HIV virus, which is known to cause AIDS.
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- HIV protease inhibitors
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HIV protease inhibitors, obtainable by chemical synthesis, inhibit or block the biological activity of the HIV protease enzyme, causing the replication of the HIV virus to terminate. These compounds, as well as pharmaceutical compositions that contain these compounds and optionally other anti-viral agents as active ingredients, are suitable for treating patients or hosts infected with the HIV virus, which is known to cause AIDS.
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- New low-density lipoprotein receptor upregulators acting via a novel mechanism
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The synthesis and biological activity of a new series of benzamides and related compounds that upregulate the expression of the low-density lipoprotein (LDL) receptor in human hepatocytes (HepG2 cells) by a novel mechanism are described. The lead compound, N-[5-[(3- cyclohexylpropionyl)amino]-2-methylphenyl]-4-hydroxybenzamide (1, RPR102359), increased the expression of the LDL receptors in HepG2 cells by 80% when tested at a concentration of 3 μM. Mevinolin (lovastatin) was found to increase the LDL receptor expression by 70% at the same concentration. In contrast to mevinolin, 1 was found to have no effect on cholesterol biosynthesis in liver homogenates or in HepG2 cells at doses where substantial upregulation of the LDL receptor was observed and thus stimulated LDL receptor expression by a novel mechanism.
- Ashton, Michael J.,Brown, Thomas J.,Fenton, Garry,Halley, Frank,Harper, Mark F.,Lockey, Peter M.,Porter, Barry,Roach, Alan G.,Stuttle, Keith A. J.,Vicker, Nigel,Walsh, Roger J. A.
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p. 3343 - 3356
(2007/10/03)
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- One pot preparation of pyrido[2,3,4-de] quinazolines and benzo[de][1,6] naphthyridines by a consecutive process involving an aza-Wittig/ electrocyclic ring-closure/heterocumulene-mediated annelation or intramolecular Diels-Alder cycloaddition sequence
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Aza Wittig-type reaction of bis(iminophosphorane)1 with one mole of isocyanate leads to the iminophosphoranes 5 which by treatment with a second mole of isocyanate afforded pyrido[2,3,4-de]quinazolines 6. Similarly, reaction with ketenes leads to the formation of benzo[de][1,6] naphthyridines 9. Direct conversion 1→6 and 1→9 were achieved using two moles of isocyanate or ketene respectively.
- Molina, Pedro,Alajarin, Mateo,Vidal, Angel
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p. 5379 - 5382
(2007/10/02)
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- Molecular Armatures. Synthesis and Structure of Troegers Base Analogues Derived from 4-, 2,4-, 3,4-, and 2,4,5-Substituted Aniline Derivatives
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The preparation of biomimetic systems designed to mimic natural receptor sites and enzymic active sites requires the development of new synthetic strategies for preparing large molecules with predictable and well-defined shapes.In this paper a number of derivatives of 6H,12H-5,11-methanodibenzodiazocines are prepared.The scope and limitations of the reaction of formaldehyde with aniline derivatives are examined.The molecules prepared have potential value as conformationally restricted armatures for the construction of biomimetic molecular systems.A crystallographic study reveals that the molecules are folded and that the angle formed by the two aryl rings ranges from 88 deg to 104 deg.Sulfonamides, bromides, alcohols, and amines can be introduced as side-chain substituents in these systems.
- Sucholeiki, Irving,Lynch, Vincent,Phan, Ly,Wilcox, Craig S.
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