- Regioselective chlorination and bromination of unprotected anilines under mild conditions using copper halides in ionic liquids
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By using ionic liquids as solvents, the chlorination or bromination of unprotected anilines at the para-position can be achieved in high yields with copper halides under mild conditions, without the need for potentially hazardous operations such as supplementing oxygen or gaseous HCl.
- Wang, Han,Wen, Kun,Nurahmat, Nurbiya,Shao, Yan,Zhang, He,Wei, Chao,Li, Ya,Shen, Yongjia,Sun, Zhihua
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Read Online
- Hypoxia-Activated Anticancer Prodrug for Bioimaging, Tracking Drug Release, and Anticancer Application
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A novel anticancer theranostic prodrug, FDU-DB-NO2, specifically activated by hypoxia for selective two-photon imaging hypoxia status, real-time tracking drug release, and solid tumor therapy was designed. The devised prodrug consists of an anticancer drug floxuridine (FDU), a fluorescence dye precursor 4′-(diethylamino)-1,1′-biphenyl-2-carboxylate (DB), and a hypoxic trigger 4-nitrobenzyl group. In normal cells, FDU-DB-NO2 is "locked". Whereas in tumor cells, the prodrug is "unlocked" by hypoxia and results in fluorescent dye 7-(diethylamino)coumarin (CM) generation along with FDU release. The amounts and rates of CM formation and FDU release were controlled by hypoxic status and increased with the decreasing of the O2 concentration. The hypoxic status, distribution of oxygen, and amount of FDU release in tumor cells, spheroids, and tumor tissue could be visualized by fluorescence. FDU-DB-NO2 showed high cytotoxicity against hypoxic MCF-7 and MCG-803 cell lines and no cytotoxicity against normoxic BRL-3A cells and exhibited effective inhibition on tumor growth of MCF-7-cell-inoculated xenograft nude mice. This strategy may provide a promising platform for selective two-photon imaging hypoxia status, real-time tracking drug release, and personalized solid tumor treatment.
- Liu, Wei,Liu, Haitong,Peng, Xiaoran,Zhou, Guoqiang,Liu, Dandan,Li, Shenghui,Zhang, Jinchao,Wang, Shuxiang
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Read Online
- Preparation method for 2,5-dibromophenol
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The invention discloses an industrial preparation method for 2,5-dibromophenol. The industrial preparation method for the 2,5-dibromophenol comprises the following steps: using 2-amino-5-nitrobenzenemethyl ether as an initial raw material, and synthesizing the 2,5-dibromophenol through a four-step reaction of performing diazotization bromination, reduction, secondary diazotization bromination anddemethylation. The obtained 2,5-dibromophenol is a black solid, the purity is 97.5%, a raw material conversion rate in each step reaches 100% respectively, and a total yield of the whole process reaches 34%.
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Paragraph 0011; 0013; 0016; 0018
(2019/02/21)
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- WEE-1 INHIBITING PYRIDOPYRIMIDINONE COMPOUNDS
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The present invention relates to compounds that are useful as inhibitors of the activity of Wee-1 kinase. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in the treatment of cancer and methods of treating cancer.
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Page/Page column 62
(2018/03/02)
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- Balancing potency, metabolic stability and permeability in pyrrolopyrimidine-based EGFR inhibitors
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The present study describes our continuous effort to develop epidermal growth factor receptor (EGFR) inhibitors based on the 6-aryl-pyrrolo[2,3-d]pyrimidin-4-amine scaffold. The activity-ADME space has been evaluated by synthesizing 43 new structures, including four variations of the 4-amino group and 34 different substitution patterns in the 6-aryl moiety. Most of the new pyrrolopyrimidines were highly active, with twelve analogues possessing lower IC50values than the commercial drug Erlotinib in enzymatic assays. Ten EGFR inhibitors were also profiled in cell studies using the Ba/F3-EGFRL858Rreporter cells, and all revealed nanomolar activity. However, some of the privileged structures in terms of potency had ADME short-comings: compounds containing amides, sulfonamides, amine and hydroxymethyl substituents in the 6-aryl group had low permeability and high efflux, derivatives having (R)-3-amino-3-phenylpropan-1-ol at C-4 induced hERG inhibition properties, and metabolic lability was seen for compounds having (S)-2-methoxy-1-phenylethan-1-amine at C-4. Based on a trade-off between enzymatic activity, cellular potency and ADME properties, (S)-2-phenyl-2-((6-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethan-1-ol appeared as the most promising drug candidate. Cellular studies indicate this compound to have therapeutic use in EGFR driven diseases.
- Han, Jin,Henriksen, Silje,N?rsett, Kristin G.,Sundby, Eirik,Hoff, B?rd Helge
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supporting information
p. 583 - 607
(2016/09/14)
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- ARYL AMIDE KINASE INHIBITORS
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The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.
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Page/Page column 194
(2015/02/02)
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- Development of 2-thioxoquinazoline-4-one derivatives as dual and selective inhibitors of dynamin-related protein 1 (Drp1) and puromycin-sensitive aminopeptidase (PSA)
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An established inhibitor ot dynamin-related protein 1 (Drp1), 3-(2,4-dichloro-5-methoxyphenyl)- 2- thioxoquinazoline-4-one (mdivi-1), was recently reported also to show potent puromycin-sensitive aminopeptidase (PSA)-inhibitory activity. Herein, we report structural development of mdivi-1 derivatives and structure-activity relationship (SAR) analysis of the synthesized compounds, as well as the structurally related PSA-specific inhibitor 3-(2,6-diethylphenyl)quinazoline-2,4-dione (PAQ-22), with the aim of identifying key structural features for inhibitory activity in order to develop selective inhibitors of Drpl, which is a potential target for treatment of Huntington's disease. Among the synthesized compounds, 3-(4-chloro3methoxyphenyl)-2-thioxoquinazoline-4-one 10g) exhibited more potent Drpl-inhibitory activity than mdivi-1 with high selectivity for Drpl over PSA.
- Numadate, Akiyoshi,Mita, Yusuke,Matsumoto, Yotaro,Fujii, Shinya,Hashimoto, Yuichi
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p. 979 - 988
(2015/02/19)
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- Synthesis and reactivity of dimethoxy-functionalised Troeger's base analogues
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Troeger's base analogues were prepared bearing methoxy groups in the 1,7-, 2,8-, 3,9- or 4,10-positions. These compounds were converted to their dihydroxy analogues in excellent yields upon treatment with boron tribromide and the 4,10-dihydroxy analogue could be prepared by directly from 4-hydroxyaniline. The synthetic utility of the dihydroxy-functionalised compounds as building blocks was demonstrated by the synthesis of a dialkoxy and a diester Troeger's base analogue.
- Malik, Qasim M.,Ijaz, Sadia,Craig, Donald C.,Try, Andrew C.
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experimental part
p. 5798 - 5805
(2011/08/21)
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- Synthesis of arylbromides from arenes and Nbromosuccinimide bromosuccinimide (NBS) in acetonitrile - A convenient method for aromatic bromination
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Regioselective and chemoselective electrophilic bromination of a wide series of activated arenes using N-bromosuccinimide (NBS) in acetonitrile occurs readily. Environmentally friendly conditions, large substrate scope, and ease of synthesis enhance the utility of this method over other electrophilic bromination conditions.
- Zysman-Colman, Eli,Arias, Karla,Siegel, Jay S.
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experimental part
p. 440 - 447
(2009/12/01)
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- SULFONAMIDE DERIVATIVE HAVING PGD2 RECEPTOR ANTAGONISTIC ACTIVITY
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A sulfonamide derivative having DP receptor antagonistic activity; and a medicinal composition and a therapeutic agent for allergic diseases which each contains the compound as an active ingredient. The derivative is a compound represented by the general formula (II): (II) (wherein ring A is an aromatic carbocycle, etc.; ring B is a nitrogenous nonaromatic heterocycle, etc.; ring C is an aromatic carbocycle, etc.; R1 is carboxy, etc.; R2's each independently is halogeno, etc.; R3 is optionally substituted alkyloxy, etc.; R4's each independently is halogeno, etc.; R5's each independently is optionally substituted alkyl, etc.; M is sulfonyl, etc.; Y is a single bond, etc.; L1 is a single bond, etc.; L2 is a single bond, etc.; k is 0, 1, 2, 3, or 4; n is 0, 1, or 2; and q is 0, 1, 2, or 3, provided that, for example, a) when ring B is a 6-membered nitrogenous heterocycle containing one or two nitrogen atoms and ring C is a benzene ring, then k is not 0), a pharmaceutically acceptable salt of the compound, or a hydrate of either.
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Page/Page column 127
(2010/11/26)
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- COMPOUND HAVING TGF-BETA INHIBITORY ACTIVITY AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
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The present invention provides compounds of formula (I) or compounds of formula (II) and pharmaceutically acceptable salts or solvates thereof. An objective of the present invention is to provide compounds having TGF2 inhibitory activity.
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Page/Page column 82
(2010/11/24)
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- Polymer-supported organotin reagents for regioselective halogenation of aromatic amines
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(Chemical Equation Presented) Polymer-supported triorganotin halides were used in the halogenation reaction of aromatic amines. Treatment of aromatic amines with n-butyllithium and polymer-supported organotin halides gave the corresponding polymer-bound N-triorganostannylamines, which by treatment with bromine or iodine monochloride gave the para-halogenated aromatic amines with high yields and high selectivities. The polymer-supported organotin halides reagents regenerated during the course of the halogenation reaction can be reused without loss of efficiency. The presence of tin residues in halogenated aromatic amines was also investigated and evaluated at under 20 ppm after three runs.
- Chretien, Jean-Mathieu,Zammattio, Francoise,Le Grognec, Erwan,Paris, Michael,Cahingt, Blanche,Montavon, Gilles,Quintard, Jean-Paul
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p. 2870 - 2873
(2007/10/03)
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- HETEROCYCLIC KINASE INHIBITORS
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Compounds having the formula (I) are useful for inhibiting protein kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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- Quinoline derivatives
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Compounds of formula I as well as pharmaceutically acceptable salts and esters thereof, wherein R1, R2, R3, A1 and A2 have the significance given in claim 1, can be used in the form of pharmaceutical preparations for the treatment or prevention of arthritis, cardiovascular diseases, diabetes, renal failure, eating disorders and obesity.
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- Acetoxylation of 6,7-dialkoxy-substituted 1,4-dihydroquinoxaline-2,3-diones (QXs) using fuming nitric acid in acetic acid: A facile synthesis of 5-acyloxy-6,7-dialkoxy QXs
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Treatment of 6,7-dialkoxy-1,4-dihydroquinoxaline-2,3-diones 3 with fuming nitric acid in acetic acid at 25°C resulted in an acetoxylation reaction, giving 5-acetoxy-6,7-dialkoxy-1,4-dihydroquinoxaline-2,3-diones 4 in moderate yields. A mechanism involving ipso attack of nitronium ion as the first step is proposed.
- Zhou, Zhang-Lin,Weber, Eckard,Keana, John F. W.
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p. 7583 - 7586
(2007/10/02)
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- N-hydroxy-5-phenyl-2-furancarboximidamides useful as cardiotonic agents
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The present invention involves certain N-hydroxy-5-phenyl-2-furancarboximidamides, pharmaceutical compositions containing such compounds, and methods for increasing the contractile force of cardiac muscle of a mammal which comprises systemically administering such compounds to a mammal.
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