- Design, synthesis, and structure activity relationship (SAR) studies of novel imidazo[1,2-a] pyridine derivatives as Nek2 inhibitors
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Never in mitosis (NIMA) related kinase 2 (Nek2) is involved in multiple cellular processes such as cell cycle checkpoint regulation, cell division, DNA damage response and cell apoptosis. Nek2 has been reported to be overexpressed in various tumors and correlated with poor prognosis. Herein, a series of imidazo[1,2-a] pyridines Nek2 inhibitors were designed, synthesized, and their biological activities were investigated. Besides, structure activity relationship analysis of these compounds were performed in the MGC-803 cell. The screening results are promising, and compound 28e shows good proliferation inhibitory activity with an IC50 of 38 nM. The results would be helpful to design and develop more effective Nek2 inhibitors for the treatment of gastric cancer.
- Chen, Yunzhong,Du, Yijie,Duan, Yanhong,Gu, Xiaofan,Li, Hongyu,Ma, Mingliang,Ren, Ziwei,Wang, Haili,Wang, Shuting,Xi, Jianbei,Zhang, Xiongwen,Zhu, Tong
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- Imidazo [1, 2 - a] pyridine derivatives and preparation method and application thereof (by machine translation)
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The invention discloses 3 -phenyl imidazo [1, 2 - a] pyridine derivatives represented by a formula (I) or 3 - (thiophene -2 substituted) imidazo [1, 2 - a] pyridine derivatives and a preparation method, and also discloses application. of the 3 -phenyimidazo [1, 2 - a] pyridine derivatives or 3 - (thiophene -2 substituted) imidazo [1, 2 - a] pyridine derivatives as a class of novel structural novel small molecule inhibitors, and the like. (by machine translation)
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Paragraph 0226;
(2019/07/29)
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- Identification of protein kinase fibroblast growth factor receptor 1 (FGFR1) inhibitors among the derivatives of 5-(5,6-dimethoxybenzimidazol-1-yl)-3-hydroxythiophene-2-carboxylic acid
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Abstract: Fibroblast growth factor receptor 1 (FGFR1) plays an important role in tumorigenesis, suggesting that inhibitors of this protein kinase may become important compounds for the development of anticancer agents. Using molecular docking approach, we have identified a novel class of FGFR1 inhibitors belonging to the derivatives of 5-(5,6-dimethoxybenzimidazol-1-yl)-3-hydroxythiophene-2-carboxylic acid. It was revealed that the most promising compound 5-(5,6-dimethoxybenzimidazol-1-yl)-3-[2-(methanesulfonyl)benzyloxy]thiophene-2-carboxylic acid methyl ester inhibits FGFR1 with an IC50 value of 150?nM in in vitro kinase assay. The structure–activity relationships have been studied, and the binding mode of this chemical class has been proposed. Graphic abstract: [Figure not available: see fulltext.]
- Volynets, Galyna,Lukashov, Sergiy,Borysenko, Iryna,Gryshchenko, Andrii,Starosyla, Sergiy,Bdzhola, Volodymyr,Ruban, Tetiana,Iatsyshyna, Anna,Lukash, Lyubov,Bilokin, Yaroslav,Yarmoluk, Sergiy
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p. 1801 - 1808
(2019/11/05)
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- Preparation method of 3-hydroxythiophene-2-carboxylate compound
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The invention provides a preparation method of a 3-hydroxythiophene-2-carboxylate compound. The preparation method comprises the following steps of enabling a formula as shown in the description to carry out a condensation reaction with E-3-methyl methoxyacrylate in an alkaline condition to form the 3-hydroxythiophene-2-carboxylate compound, wherein R is selected from any one of C1 to C10 alkyl and C2 to C10 alkenyl. The formula as shown in the description and the E-3-methyl methoxyacrylate are adopted as raw materials, and are enabled to carry out the condensation reaction in the alkaline condition to form a thiophene ring; the reaction is easy to carry out; the reaction condition is easy to control; and the product yield is higher in a proper condition. The cost of the E-3-methyl methoxyacrylate is lower compared with that of 2-methyl chloroacrylate or methyl propiolate; and therefore, the synthetic process cost of the 3-hydroxythiophene-2-carboxylate compound is decreased.
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Paragraph 0034-0071
(2019/02/10)
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- SMALL MOLECULE INHIBITORS OF NEK2 AND USES THEREOF
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This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having an imidazole pyrimidine structure which function as inhibitors of NEK2 protein, and their use as therapeutics for the treatment of cancer and other diseases.
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Page/Page column 49
(2018/05/24)
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- 3-alkoxy thiophene derivative and preparation method thereof
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The invention provides a novel 3-alkoxy thiophene derivative and a preparation method thereof. The structure of the 3-alkoxy thiophene derivative is as shown in a chemical formula 1. The preparation method comprises the following steps that 1, a compound of a chemical formula 2 reacts with a compound of a chemical formula 3 to obtain a reaction product, the reaction product is subjected to hydrolysis, and a compound of a chemical formula 4 is obtained; 2, the obtained compound of the chemical formula 4 is subjected to a mono-alkylation reaction in a solvent, and a compound of a chemical formula 5 is obtained; 3, the obtained compound of the chemical formula 5 is heated to 80 DEG C to 300 DEG C under the condition of being free of solvent for a decarboxylation reaction; in the chemical formulas, R1 and R2 each independently adopts an alkyl group, and X adopts a halogen. The preparation method has the advantage of being capable of efficiently preparing the 3-alkoxy thiophene derivative in high yield.
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Paragraph 0139; 0140; 0141; 0142; 0143; 0144-0147
(2017/01/02)
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- 3-Alkoxy-4-bromothiophenes: General synthesis of monomers and regio-selective preparation of two dimers
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3-Alkoxy-4-bromothiophenes were synthesized in three steps from the readily available methyl 2-carboxylate-3-hydroxythiophene and two isomers of bithiophenes based on the 3-bromo-4-methoxythiophene moiety were regio-selectively prepared.
- Savitha, Gurunathan,Hergué, Noémie,Guilmet, Erwan,Allain, Magali,Frère, Pierre
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supporting information; experimental part
p. 1288 - 1291
(2011/03/22)
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- DNA-BINDING POLYMERS
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Methods and compositions are provided for forming complexes between dsDNA and novel DNA-binding polymers comprising N-terminal thiophene-containing moieties which exhibit selectivity for T-A base pairs. By appropriate choice of target sequences and DNA-binding polymers, complexes comprising polymer-DNA are obtained with high association constants. The formation of complexes can be used for identification of specific dsDNA sequences, for inhibiting gene transcription, and as a therapeutic for inhibiting proliferation of undesired cells or modulation of expression of specific genes.
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Page/Page column 16
(2009/07/03)
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- CB1-MODULATING COMPOUNDS AND THEIR USE
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Disclosed herein is a compound of Formula (I). Also disclosed herein is a method of modulating the activity of a cannabinoid receptor using a compound of Formula (I). Furthermore, disclosed herein is a method of treating a disease or condition that would
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Page/Page column 70
(2008/12/05)
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- DNA-binding polymers
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Methods and compositions are provided for forming complexes between dsDNA and novel DNA-binding polymers comprising N-terminal thiophene-containing moieties which exhibit selectivity for T-A base pairs. By appropriate choice of target sequences and DNA-binding polymers, complexes comprising polymer-DNA are obtained with high association constants. The formation of complexes can be used for identification of specific dsDNA sequences, for inhibiting gene transcription, and as a therapeutic for inhibiting proliferation of undesired cells or modulation of expression of specific genes.
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- Shape selective recognition of T·A base pairs by hairpin polyamides containing N-terminal 3-methoxy (and 3-Chloro) thiophene residues
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Hairpin polyamides selectively recognize predetermined DNA sequences with affinities comparable to naturally occurring proteins. Internal side-by-side pairs of unsymmetrical aromatic rings within the minor groove of DNA distinguish each of the four Watson-Crick base pairs. In contrast, N-terminal ring pairs exhibit less specificity, with the exception of Im/Py targeting G·C base pairs. In an effort to explore the sequence specificity of new ring pairs, a series of hairpin polyamides containing 3-substituted-thiophene-2-carboxamide residues at the N-terminus was synthesized. An N-terminal 3-methoxy (or 3-chloro) thiophene residue paired opposite Py displayed 6- (and 3-) fold selectivity for T·A relative to A·T base pair, while disfavoring G,C base pairs by >200-fold. Our data suggests shape selective recognition with projection of the 3-thiophene substituent (methoxy or chloro) to the floor of the minor groove.
- Foister, Shane,Marques, Michael A.,Doss, Raymond M.,Dervan, Peter B.
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p. 4333 - 4340
(2007/10/03)
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- Toward an understanding of the chemical etiology for DNA minor-groove recognition by polyamides
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Crescent-shaped polyamides composed of aromatic amino acids, i.e., 1-methyl-1H-imidazole Im, 1-methyl-1H-pyrrole Py, and 3-hydroxy-1H-pyrrole Hp, bind in the minor groove of DNA as 2:1 and 1:1 ligand/DNA complexes. DNA-Sequence specificity can be attributed to shape-selective recognition and the unique corners or pairs of corners presented by each heterocycle(s) to the edges of the base pairs on the floor of the minor groove. Here we examine the relationship between heterocycle structure and DNA-sequence specificity for a family of five-membered aromatic amino acids. By means of quantitative DNase-I footprinting, the recognition behavior of polyamides containing eight different aromatic amino acids, i.e., 1-methyl-1H-pyrazole Pz, 1H-pyrrole Nh, 5-methylthiazole Nt, 4-methylthiazole Th, 3-methylthiophene Tn, thiophene Tp, 3-hydroxythiophene Ht, and furan Fr, were compared with the polyamides containing the parent-ring amino acids Py, Im, and Hp for their ability to discriminate between the four Watson - Crick base pairs in the DNA minor groove. Analysis of the data and molecular modeling showed that the geometry inherent to each heterocycle plays a significant role in the ability of polyamides to differentiate between DNA sequences. Binding appears sensitive to changes in curvature complementarity between the polyamide and DNA. The Tn/Py pair affords a modest 3-fold discrimination of T · A vs. A · T and suggests that an S-atom in the thiophene ring prefers to lie opposite T not A.
- Marques, Michael A.,Doss, Raymond M.,Urbach, Adam R.,Dervan, Peter B.
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p. 4485 - 4517
(2007/10/03)
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- Synthesis and anthelmintic activity of 7-hydroxy-5-oxo-5H-thieno[3,2- b]pyran-6-carboxanilides and -6-thiocarboxanilides
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7-Hydroxy-5-oxo-5H-thieno[3,2-b]pyran-6-carboxanilides and -6- thiocarboxanilides represent a novel series of anthelmintic compounds, with broad-spectrum activity against important parasitic nematodes in sheep and dogs. In particular, an improved efficacy against Trichostrongylus colubriformis in sheep over the related 3-carbamoyl-4-hydroxycoumarins has been noted. New synthetic routes to the key intermediate, 7- hydroxythieno[3,2-b]pyran-5-one, have been developed.
- Plant,Harder,Mencke,Bertram
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p. 351 - 358
(2007/10/03)
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- Thienyl-nonatetraenoic acid derivatives with anti-rheumatic activity
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Novel 9-thienyl-3,7-dimethyl-2,4,6,8-nonatetraenoic acids wherein the thiophene group is substituted with an alkyl and alkoxy group, and derivatives thereof can be used as disease modifying anti-rheumatic agents and immunosuppressants.
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- N-1H-tetrazol-5-yl-2-thiophene carboxamides, N-1H-tetrazol-5-yl-2-pyrrole carboxamides, N-1H-tetrazol-5-yl-2-furan carboxamides, and anti-allergic and anti-inflammatory use thereof
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The present invention is for compounds having the formula of N-1H-tetrazol-5-yl-2-thiophenecarboxamides, N-1H-tetrazol-5-yl-2-pyrrolecarboxamides, N-1H-tetrazol-5-yl-2-furancarboxamides or analogs of each of the carboxamides. The compounds are useful for the treatment of allergic or inflammatory conditions or diseases. Thus, pharmaceutical compositions and methods of use are also the invention. Processes of preparation for the compounds are also the invention.
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- Thiophene compounds and their manufacture
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New thiophene compounds and a new process for the manufacture of thiophene compounds by dehydrogenating dihydrothiophene with certain halogen compounds. The products are starting materials for the manufacture of pharmaceuticals, dyes and plant protection agents and, in particular, for the manufacture of additives to foodstuffs, feeds, beverages and pharmaceuticals.
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- Aromatization of Dihydrothiophenes. Thiophenesaccharin: A Sweet Surprise
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Sulfuryl chloride has been shown to be highly effective in the dehydrogenation of 3,4-disubstituted-2,5-dihydrothiophenes and 2,3-disubstituted-4,5-dihydrothiophenes, in which the 3,4 and 2,3 substitutents are part of a β-keto carbonyl functionality or it
- Rossy, Phillip A.,Hoffmann, Werner,Mueller, Norbert
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p. 617 - 620
(2007/10/02)
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