- Fluorescent biaryl uracils with C5-dihydro- And quinazolinone heterocyclic appendages in PNA
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There has been much effort to exploit fluorescence techniques in the detection of nucleic acids. Canonical nucleic acids are essentially nonfluorescent; however, the modification of the nucleobase has proved to be a fruitful way to engender fluorescence. Much of the chemistry used to prepare modified nucleobases relies on expensive transition metal catalysts. In this work, we describe the synthesis of biaryl quinazolinone-uracil nucleobase analogs prepared by the condensation of anthranilamide derivatives and 5-formyluracil using inexpensive copper salts. A selection of modified nucleobases were prepared, and the effect of methoxy- or nitro- group substitution on the photophysical properties was examined. Both the dihydroquinazolinone and quinazolinone modified uracils have much larger molar absorptivity (~4-8×) than natural uracil and produce modest blue fluorescence. The quinazolinone-modified uracils display higher quantum yields than the corresponding dihydroquinazolinones and also show temperature and viscosity dependent emission consistent with molecular rotor behavior. Peptide nucleic acid (PNA) monomers possessing quinazolinone modified uracils were prepared and incorporated into oligomers. In the sequence context examined, the nitro-substituted, methoxy-substituted and unmodified quinazolinone inserts resulted in a stabilization (?Tm = +4.0/insert; +2.0/insert; +1.0/insert, respectively) relative to control PNA sequence upon hybridization to complementary DNA. All three derivatives responded to hybridization by the “turn-on” of fluorescence intensity by ca. 3-to-4 fold and may find use as probes for complementary DNA sequences.
- Heidari, Ali,Ghorbani-Choghamarani, Arash,Hajjami, Maryam,Hudson, Robert H.E.
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- New spiro pyrrole[2, 1-b]quinazolone derivative, preparation method and application thereof
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The invention relates to a new spiro pyrrole[2, 1-b]quinazolone derivative, a preparation method and application thereof. The new spiro pyrrole[2, 1-b]quinazolone derivative is synthesized by using asimple method. The yield is high, the production cost is
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Paragraph 0140-0142
(2020/11/09)
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- Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one containing 4,5-dihydrothiazole-2-thiol derivatives against Meloidogyne incognita
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A series of novel 1,2,3-benzotriazin-4-one derivatives containing 4,5-dihydrothiazole-2-thiol were synthesized and characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The bioassay results showed that compounds 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-7-methoxybenzo[d][1–3]triazin-4(3H)-one, 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-6-nitrobenzo[d][1–3]triazin-4(3H)-one, 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita at the concentration of 10.0 mg L?1 in vivo. Compound 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one showed excellent nematicidal activity with inhibition 68.3% at a concentration of 1.0 mg L?1. It suggested that the structure of 1,2,3-benzotriazin-4-one containing 4,5-dihydro-thiazole-2-thiol could be optimized further.
- Chen, Xiulei,Zhou, Zhen,Li, Zhong,Xu, Xiaoyong
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p. 194 - 200
(2019/09/13)
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- Amino evodiamine derivative and preparation method and application thereof
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The invention discloses an amino evodiamine derivative and a preparation method and application thereof. A carboline compound and N-methyl-7-nitro isatoic anhydride are used for preparing a 2-nitro evodiamine derivative, and the 2-nitro evodiamine derivative is reduced to obtain the amino evodiamine derivative. A cytotoxicity experiment is performed by using a CCK-8 method, the anti-proliferationeffect of the compound on breast cancer MDA-MB-231 cells, colon cancer SW620 cells and normal liver LO2 cells is evaluated, and cell apoptosis detection is performed by using FITC/PI double staining;experiments show that compared with evodiamine, the compound 2-NH2-EVO has a very strong inhibition effect on breast cancer cells MDA-MB-231, the IC50 value is 0.79 uM, meanwhile, cell apoptosis can be remarkably induced, and the compound 2-NH2-EVO is expected to be developed into an anti-cancer drug with potential.
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Paragraph 0010; 0014
(2020/09/16)
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- Amino evodiamine polymer micelle as well as preparation method and application thereof
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The invention discloses an amino evodiamine polymer micelle as well as a preparation method and application thereof. The preparation method comprises the following steps: preparing a 2-nitro evodiamine derivative from a carboline compound and N-methyl-7-nitro isatoic anhydride, reducing the 2-nitro evodiamine derivative to obtain an amino evodiamine derivative, and reacting a polymer with amino evodiamine to prepare an amino evodiamine polymer conjugate; and then carrying out self-assembly on the amino evodiamine polymer conjugate to obtain the amino evodiamine polymer micelle. The water solubility and bioavailability of a drug are improved, the drug is combined with a nanotechnology, a nano drug loading system is developed for drug delivery, and the nano drug can be passively enriched intumor tissues in a targeting manner through an EPR effect.
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Paragraph 0017-0018
(2020/10/04)
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- Doxorubicin-loaded polymeric micelle as well as preparation method and application thereof
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The present invention discloses a doxorubicin-loaded polymeric micelle as well as a preparation method and application thereof. Novel amino evodiamine is adopted to react with polyethylene glycol, a micelle obtained by self-assembly is used as a carrier to load doxorubicin, a prepared mPEG-CO-NH-EVO micelle and a mPEG-CO-NH-EVO-OCH3 micelle have low toxicity to normal hepatocytes so that the two amphipathic polymeric micelles are used as carriers to load DOX to prepare DOX-loaded polymeric micelles, namely a mPEG-CO-NH-EVO/DOX micelle and a mPEG-CO-NH-EVO-OCH3/DOX micelle, and DOX enters hydrophobic shells of the micelles due to the dialysis effect; shapes of the micelles are represented by using a transmission electron microscope and a scanning electron microscope, and the drug loading efficiency and encapsulation efficiency of DOX are tested and calculated by using an ultraviolet spectrophotometer; and finally, evaluating the cytotoxicity by using a CCK-8 method. Shown by cytotoxicity tests, a DOX-loaded polymer has an effect on inhibiting breast cancer cells and particularly has greatly reduced toxicity to the normal hepatocytes.
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Paragraph 0014; 0015
(2020/10/04)
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- Synthesis and nematicidal evaluation of 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker against Meloidogyne incognita
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To explore new skeleton with nematicidal activity, a series of novel 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker were synthesized and varied fragments were also introduced to increase structure diversity of the new skeleton. Their inhibitory activities in vivo were evaluated against Meloidogyne incognita. The newly prepared compounds A6, A8, A21, A28 and A38 exhibited more than 50% inhibition at the concentration of 20 mg/L. Especially compound A6 displayed 71.4% inhibition against Meloidogyne incognita at the concentration of 20 mg/L. The nematicidal activities varied significantly depending on the types and positions of the substituents, which provided guidance for further structure modification.
- Chen, Xiulei,Jia, Haowu,Li, Zhong,Xu, Xiaoyong
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supporting information
p. 1207 - 1213
(2019/03/29)
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- Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: Preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives
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A convenient two-step synthesis of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate derivatives has been developed starting from commercially available 2-aminobenzoic acids. In step 1, the anthranilic acids are smoothly converted to isatoic anhydrides using solid triphosgene in THF. In step 2, the anhydride electrophiles are reacted with the sodium enolate of ethyl acetoacetate, generated from sodium hydroxide, in warm N,N-dimethylacetamide resulting in the formation of substituted quinolines. A degradation–buildup strategy of the ethyl ester at the 3-position allowed for the construction of the α-hydroxyacetic acid residue required for the synthesis of key arylquinolines involved in an HIV integrase project.
- Jentsch, Nicholas G.,Hume, Jared D.,Crull, Emily B.,Beauti, Samer M.,Pham, Amy H.,Pigza, Julie A.,Kessl, Jacques J.,Donahue, Matthew G.
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p. 2529 - 2536
(2018/10/21)
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- Synthesis and Nematicidal Activities of 1,2,3-Benzotriazin-4-one Derivatives against Meloidogyne incognita
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A series of novel 1,2,3-benzotriazin-4-one derivatives were synthesized by the reaction of 3-bromoalkyl-1,2,3-benzotriazin-4-ones with potassium salt of 2-cyanoimino-4-oxothiazolidine in the presence of potassium iodide. Nematicidal assays in vivo showed that some of them exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita, up to 100% at the concentration of 10.0 mg L-1, which indicated that 1,2,3-benzotriazin-4-one derivatives might be potential for novel promising nematicides. The nematicidal activity was influenced by the combination of substituent type, substituted position, and linker length in the molecule. The inhibition rate data at the concentrations of 5.0 and 1.0 mg L-1 for the compounds with high inhibitory activities were also provided. When tested in vitro, none of them showed direct inhibition against M. incognita. The investigation of a significant difference between in vivo and in vitro data is in progress.
- Wang, Gaolei,Chen, Xiulei,Deng, Yayun,Li, Zhong,Xu, Xiaoyong
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p. 6883 - 6889
(2015/08/18)
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- METHOD OF PRODUCING NITROGEN-CONTAINING HETEROCYCLIC COMPOUND
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PROBLEM TO BE SOLVED: To provide a chemical compound production method realizing easy and high-yield production of a nitrogen-containing heterocyclic compound useful as a synthetic intermediate and the like in many fields such as medicine, agriculture and synthetic resin additives. SOLUTION: In the production method, an ortho-substituted benzene azide derivative represented by formula (1) is reacted with carbon dioxide in the presence of a reductant to obtain a compound represented by formula (2). [R is H and/or a substituent; A is an intramolecular cyclizable group; and B is a divalent linking group of C, N and O. COPYRIGHT: (C)2016,JPOandINPIT
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Paragraph 0045
(2016/10/08)
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- INDAZOLE COMPOUNDS USEFUL AS KETOHEXOKINASE INHIBITORS
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The present invention is directed to substituted indazole compounds, pharmaceutical compositions of these compounds and methods of use thereof. The compounds of the present invention are ketohexokinase (KHK) inhibitors, useful for treating or ameliorating a KHK mediated metabolic disorders and/or diseases such as obesity, Type II diabetes mellitus and Metabolic Syndrome X.
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Page/Page column 20
(2011/11/06)
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- Electron density guided fragment-based lead discovery of ketohexokinase inhibitors
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A fragment-based drug design paradigm has been successfully applied in the discovery of lead series of ketohexokinase inhibitors. The paradigm consists of three iterations of design, synthesis, and X-ray crystallographic screening to progress low molecula
- Gibbs, Alan C.,Abad, Marta C.,Zhang, Xuqing,Tounge, Brett A.,Lewandowski, Francis A.,Struble, Geoffrey T.,Sun, Weimei,Sui, Zhihua,Kuo, Lawrence C.
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experimental part
p. 7979 - 7991
(2011/03/18)
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- PYRAZOLOQUINOLONE DERIVATIVE AND USE THEREOF
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The present invention provides a pyarzoloquinolone derivative having kinase inhibitory activity. The derivative is represented by the formula: wherein R1 is an aryl group which may be substituted, or an aromatic heterocyclic group which may be
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Page/Page column 51
(2010/11/24)
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- Synthesis of quinazoline-2,4-dione and naphthalimide derivatives as new 5-HT3 receptor antagonists
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New potent 5-HT3 receptor antagonists have been designed from the naphthalimide moiety and a quinuclidine heterocycle and the structure-activity relationships are discussed here on the basis of the nature of the substituent on the aromatic system. The biological activity of the compounds was evaluated in binding assays with [3H]BRL-43694 and by inhibition of the Bezold-Jarisch reflex. Compound 22 with a 4-amino substituent was equipotent to the reference compounds. In contrast to the benzamide derivatives, the activity resides essentially in the (R) enantiomer (K(i) = 0.15 ± 0.05 nM, ID50 = 1.6 μg/kg/iv) and it is demonstrated that the additional carbonyl group is involved in the inversion of the enantioselectivity of the receptor. Conformational studies of (R)-22 demonstrated the presence of a locked structure with 4 minimal energy conformers which were compared to those of (S)-zacopride. The superimposition of the putative active conformers emphasized the presence of a second polar group in the binding site. The fluorescent properties of the compounds were studied and indicate that (R)-22 and its derivatives may be promising tools for the direct visualization of 5-HT3 receptors.
- Langlois,Soulier,Rampillon,Gallais,Bremont,Shen,Yang,Giudice,Sureau
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p. 925 - 940
(2007/10/02)
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