- Intramolecular Povarov Reactions for the Synthesis of Chromenopyridine Fused 2-Pyridone Polyheterocycles Binding to α-Synuclein and Amyloid-β Fibrils
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A BF3·OEt2 catalyzed intramolecular Povarov reaction was used to synthesize 15 chromenopyridine fused thiazolino-2-pyridone peptidomimetics. The reaction works with several O-alkylated salicylaldehydes and amino functionalized thiazolino-2-pyridones, to generate polyheterocycles with diverse substitution. The synthesized compounds were screened for their ability to bind α-synuclein and amyloid β fibrils in vitro. Analogues substituted with a nitro group bind to mature amyloid fibrils, and the activity moreover depends on the positioning of this functional group.
- Adolfsson, Dan E.,Tyagi, Mohit,Singh, Pardeep,Deuschmann, Adrian,?dén, J?rgen,Gharibyan, Anna L.,Jayaweera, Sanduni Wasana,Lindgren, Anders E. G.,Olofsson, Anders,Almqvist, Fredrik
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p. 14174 - 14189
(2020/11/13)
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- Fast-response formaldehyde fluorescent probe as well as preparation method and application thereof
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The invention relates to a fast-response formaldehyde fluorescent probe as well as a preparation method and application thereof, and belongs to the technical field of fast formaldehyde detection. Theprobe uses coumarin as a matrix; diazanyl is used as a reaction group to react with formaldehyde; the fast detection on the formaldehyde is realized through the fluorescent change of the probe. The response time of the formaldehyde is as low as 220 s; the fluorescence intensity at 503 nm is obviously enhanced. The fast and nondestructive detection on the formaldehyde in a water solution is realized by the probe; the detection lower limit of the formaldehyde is 5*10 mol/L. The probe can resist the interference of cysteine, glutathione, L-arginine, sodium citrate, homocysteine, phenylalanine, alanine, glutamic acid, glycine, methionine, sodium ascorbate, Ca, Na, Mg, K and hydrogen peroxide; the selective specificity is high. The probe is applied to the fast detection on thecontent of the formaldehyde in food and textiles; various indexes are excellent; the fast detection requirements are completely met. The probe can also detect the formaldehyde in living cells througha confocal fluorescence microscope, and the fluorescence imaging is performed.
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Paragraph 0039
(2019/04/11)
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- 3. 4 - diphenyl - 4H - 1, 2, 4 - triazole derivative and its preparation method and application (by machine translation)
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The invention discloses 3, 4 - diphenyl - 4H - 1, 2, 4 - triazole derivative and its preparation method and application. In particular, the invention relates to the formula (I) structure of 3, 4 - diphenyl - 4H - 1, 2, 4 - triazole derivatives, its stereoisomers or its pharmaceutically acceptable salt, formula (I) in the definition of each substituent is as defined in the specification. These structure of novel compound with heat shock protein HSP90 inhibitory activity, can be used for treating cancer, neurodegenerative diseases, inflammatory diseases, autoimmune diseases, ischemic brain injury and the like, it has broad application prospects. (by machine translation)
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Paragraph 0119; 0120; 0121; 0122
(2017/07/01)
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- Pyrimidine heterocyclic compounds, pyrimidine heterocyclic compound salts, and preparation method and application thereof
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The invention provides pyrimidine heterocyclic compounds, pyrimidine heterocyclic compound salts, and a preparation method and application thereof. According to the pyrimidine heterocyclic compounds provided by the invention, specific Rq is selected, so that the obtained compounds have favorable drug resistance and long half life when being used as the medicine for treating or preventing HIV. The compounds have the advantages of high activity, low toxicity and high stability.
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Paragraph 0174; 0175; 0176; 0177
(2017/07/26)
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- Copper-Catalyzed Preparation of 2-Aryl-3-cyanobenzofurans with Bright Blue Photoluminescence
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Copper-catalyzed cascade synthesis of 2-aryl-3-cyanobenzofurans from o-hydroxybenzaldehydes and arylacetonitriles in the presence of copper acetate and sodium methoxide is reported. The synthesized 2-aryl-3-cyanobenzofurans emit bright blue under UV light with a quantum yield up to 88.9%. (Chemical Equation Presented).
- Zhang, Lianpeng,Peng, Zhixing,Wen, Qiaodong,Li, Xihui,Lu, Ping,Wang, Yanguang
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p. 728 - 731
(2016/03/01)
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- Discovery of BI 207524, an indole diamide NS5B thumb pocket 1 inhibitor with improved potency for the potential treatment of chronic hepatitis C virus infection
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The development of interferon-free regimens for the treatment of chronic HCV infection constitutes a preferred option that is expected in the future to provide patients with improved efficacy, better tolerability, and reduced risk for emergence of drug-resistant virus. We have pursued non-nucleoside NS5B polymerase allosteric inhibitors as combination partners with other direct acting antivirals (DAAs) having a complementary mechanism of action. Herein, we describe the discovery of a potent follow-up compound (BI 207524, 27) to the first thumb pocket 1 NS5B inhibitor to demonstrate antiviral activity in genotype 1 HCV infected patients, BILB 1941 (1). Cell-based replicon potency was significantly improved through electronic modulation of the pKa of the carboxylic acid function of the lead molecule. Subsequent ADME-PK optimization lead to 27, a predicted low clearance compound in man. The preclinical profile of inhibitor 27 is discussed, as well as the identification of a genotoxic metabolite that led to the discontinuation of the development of this compound.
- Beaulieu, Pierre L.,Anderson, Paul C.,Bethell, Richard,B?s, Michael,Bousquet, Yves,Brochu, Christian,Cordingley, Michael G.,Fazal, Gulrez,Garneau, Michel,Gillard, James R.,Kawai, Stephen,Marquis, Martin,McKercher, Ginette,Poupart, Marc-André,Stammers, Timothy,Thavonekham, Bounkham,Wernic, Dominik,Duan, Jianmin,Kukolj, George
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p. 10130 - 10143
(2015/02/05)
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- Total synthesis and evaluation of iso-duocarmycin SA and iso-yatakemycin
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The total synthesis and evaluation of iso-duocarmycin SA (5) and iso-yatakemycin (6), representing key analogues of the corresponding natural products incorporating an isomeric alkylation subunit, are detailed. This pyrrole isomer of the natural alkylation subunit displayed an enhanced reaction regioselectivity and a 2-fold diminished stability. Although still exceptionally potent, the /so-duocarmycin SA derivatives and natural product analogues exhibited a corresponding approximate 3-5-fold reduction in cytotoxic activity [L1210 IC50 for (+)-iso-duocarmycin SA = 50 pM and for (+)-/so-yatakemycin = 15 pM] consistent with their placement on a parabolic relationship correlating activity with reactivity. The DNA alkylation selectivity of the resulting key natural product analogues was unaltered by the structure modification in spite of the minor-groove presentation of a potential H-bond donor. Additionally, a unique ortho-spirocyclization with such derivatives was explored via the preparation, characterization, and evaluation of 34 that is incapable of themore conventional para-spirocyclization. Although 34 proved sufficientl y stable for isolation and characterization, it displayed little stability in protic solvents (f1/2 = 0.19hatpH3, t 1/2 = 0.20 h at pH 7), a pH-independent (H+ independent) solvolysisrate profile at pH 3/4-7, and a much reduced cytotoxic potency, but a D NA alkylation selectivity and efficiency comparable to those of duocarmycin SA and iso-duocarmycin SA. The implications of these observations onthe source of the DNA alkylation selectivity and catalysis for this cla ss of natural products are discussed.
- MacMillan, Karen S.,Nguyen, Trihn,Hwang, Inkyu,Boger, Dale L.
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supporting information; experimental part
p. 1187 - 1194
(2009/06/28)
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- VIRAL POLYMERASE INHIBITORS
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A compound, represented by formula (I) or an enantiomer, diastereoisomer or tautomer thereof : wherein either A or B is nitrogen and the other B or A is C, and the radicals R1, R2, R3, R5, R6, R7, R9, and R10 are as defined herein, or a salt, ester or derivative thereof as viral polymerase inhibitors. The compound is used as an inhibitor of RNA dependent RNA polymerases, particulary those viral polymerases within the Flaviviridae family, more particulary to HCV polymerase.
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Page/Page column 49; 50
(2010/02/15)
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- BENZOTHIOPHENE UREA, BENZOFURANE UREA, AND INDOLE UREA, AND USE OF THE SAME AS ALPHA-7 ACHR AGONISTS
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The invention relates to novel benzothiophene urea, benzofurane urea, and indole urea, and to the use thereof for producing medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration power, learning capacity and/or memory retention.
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Page/Page column 45-46
(2010/11/30)
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- Nitroaryl phosphoramide compositions and methods for targeting and inhibiting undesirable cell growth or proliferation
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The present invention relates to nitroaryl-substituted phosphoramide prodrug compounds and methods of producing the same for use in targeting and inhibiting undesirable cell growth or proliferation.
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- Nitrobenzocyclophosphamides as potential prodrugs for bioreductive activation: Synthesis, stability, enzymatic reduction, and antiproliferative activity in cell culture
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In efforts to obtain potential anticancer prodrugs for gene-directed enzyme prodrug therapy using Eschericia coli nitroreductase, a series of four benzocyclophosphamide analogues were designed and synthesized incorporating a strategically placed nitro group in a position para to the benzylic carbon for reductive activation. All four analogues were found to be stable in phosphate buffer at pH 7.4 and 37 °C and were good substrates of E. coli nitroreductase with half lives between 7 and 24 min at pH 7.0 and 37 °C. However, only two analogues 6a and 6c, both with a benzylic oxygen in the phosphorinane ring para to the nitro group, showed a modest 33-36-fold enhanced cytotoxicity in E. coli nitroreductase-expressing cells. These results suggest that good substrate activity and the para benzylic oxygen are required for activation by E. coli nitroreductase. Compounds 6a and 6c represent a new structure type for reductive activation and a lead for further modification in the development of better analogues with improved selective toxicity to be used in gene-directed enzyme prodrug therapy.
- Li, Zhuorong,Han, Jiye,Jiang, Yongying,Browne, Patrick,Knox, Richard J.,Hu, Longqin
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p. 4171 - 4178
(2007/10/03)
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