- Design, synthesis and anticancer evaluation of 3-methyl-1H-indazole derivatives as novel selective bromodomain-containing protein 4 inhibitors
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Bromodomain-containing Protein 4 (BRD4), an ‘epigenetic reader’, regulates chromatin structure and gene expression via recognizing and binding acetylated lysine in histones. BRD4 has become a therapeutic target for cancers because it promotes the expression of the tumor genes, such as c-Myc, NF-κB, and Bcl-2. In this study, a new series of 3-methyl-1H-indazole derivatives were designed via virtual screening and structure-based optimization. All compounds were synthesized and evaluated for their inhibitory activities to BRD4-BD1 and their antiproliferative effects in cancer cell lines. Among them, several compounds (such as 9d, 9u and 9w) exhibited strong BRD4-BD1 affinities and inhibition activities, and potently suppressed MV4;11 cancer cell line proliferation. Among them, compound 9d showed excellent selectivity for BRD4 and effectively suppressed c-Myc, the downstream protein of BRD4. This study provided new lead compounds for further biological evaluation on BRD4.
- Dong, Ru,Li, Wen,Sun, Li-Ping,Wang, Chao,Wang, Min,Xu, Yong,Zhang, Cheng,Zhang, Jin-Yang,Zhou, Xin
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- New catalytic performance of immobilized sulfuric acid on activated charcoal for n-formylation of amines with ethyl formate
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Summary: Simple and highly efficient procedure for N-formylation of various amines was carried out in the presence of the immobilized sufuric acid on activated charcoal as an efficient promoter system. All reactions were taken place in refluxing ethyl formate (54 °C) under mild reaction conditions. The product formamides were obtained in high to excellent yields (83-95%) within 4-80 min.
- Abdollahi, Mohammad,Zeynizadeh, Behzad,Sadighnia, Leila
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p. 619 - 627
(2017/11/06)
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- Design, synthesis and biological evaluation of novel 4-(2-fluorophenoxy)quinoline derivatives as selective c-Met inhibitors
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Two novel series of 6,7-disubstituted-4-(2-fluorophenoxy)quinoline derivatives bearing 1H-imidazole-4-carboxamido or (E)-3-hydrosulfonylacrylamido motifs (16–31 and 32–42) were designed, synthesized and evaluated for their in vitro cytotoxic activity. Most of the compounds exhibited moderate to excellent potency against tested three cell lines, and fifteen compounds were further examined for their inhibitory activity against c-Met kinase. The most promising compound 16 (c-Met kinase [IC50]?=?1.1?nM) demonstrated high selectivity and remarkable cytotoxicity against HT-29, MKN-45 and A549 cells with IC50values of 0.08, 0.22 and 0.07?μM, which were 3.1-, 1.4- and 2.1-fold more active than Foretinib. The preliminary structure-activity relationships as well as molecular docking disclosed that 1H-imidazole-4-carboxamido as a linker was of great importance for the antitumor activity.
- Wang, Xiaoqiang,Jiang, Nan,Zhao, Sijia,Xi, Shuancheng,Wang, Jiao,Jing, Tongfei,Zhang, Wenyu,Guo, Ming,Gong, Ping,Zhai, Xin
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p. 886 - 896
(2017/02/05)
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- Design and Synthesis of Novel 4-Phenoxyquinolines Bearing 3-Hydrosulfonylacrylamido or 1H-Imidazole-4-carboxamido Scaffolds as c-Met Kinase Inhibitors
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A series of novel 6,7-disubstituted-4-phenoxyquinoline derivatives bearing (E)-3-hydrosulfonylacrylamido or 1H-imidazole-4-carboxamido moieties were designed, synthesized and evaluated for their cytotoxicity against A549, MKN-45, and HT-29 cancer cell lines in vitro. All the target compounds showed moderate to significant cytotoxic activity against the tested cells with IC50 values ranging from 0.13 to 2.65 μM. Five of them were further examined for their inhibitory activity against c-Met kinase, which identified compound 30 as a promising agent (c-Met IC50 = 1.52 nM) with IC50 values of 0.24, 0.45, and 0.13 μM against HT-29, MKN-45, and A549 cells, respectively.
- Wang, Jiao,Xie, Lijun,Wang, Yu,Wang, Xiaoqiang,Xi, Shuancheng,Zeng, Tianfang,Gong, Ping,Zhai, Xin
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- Silver-Catalyzed Chemoselective [4+2] Annulation of Two Isocyanides: A General Route to Pyridone-Fused Carbo- and Heterocycles
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A silver-catalyzed chemoselective [4+2] annulation of aryl and heteroaryl isocyanides with α-substituted isocyanoacetamides was developed for the facile and efficient synthesis of 2-aminoquinolones, naphthyridines, and phenanthrolines. A mechanism for this multistep domino reaction is proposed on the basis of a13C-labeling experiment, according to which an unprecedented chemoselective heterodimerization of two different isocyanides generates an α-amidoketenimine intermediate, which undergoes 1,3-amino migration to form an α-imidoylketene, followed by 6 π electrocyclization.
- Hu, Zhongyan,Dong, Jinhuan,Men, Yang,Lin, Zhichen,Cai, Jinxiong,Xu, Xianxiu
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supporting information
p. 1805 - 1809
(2017/02/05)
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- NaY zeolite functionalized by sulfamic acid/Cu(OAc)2 as a new and reusable heterogeneous hybrid catalyst for efficient solvent-free formylation of amines
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NaY zeolite functionalized by sulfamic acid/Cu(OAc)2 [NaY/SA/Cu(II)] was synthesized and used as a new, efficient and recyclable catalyst for preparation of formamides. This novel organic-inorganic hybrid catalyst was characterized by several techniques such as FT-IR, XRD, SEM, EDX and TG analysis. Chemoselectivity, easy procedure, excellent yields, very short reaction times, solvent-free and mild reaction conditions are some benefits of this new protocol.
- Kazemi, Samira,Mobinikhaledi, Akbar,Zendehdel, Mojgan
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p. 1767 - 1772
(2017/07/27)
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- INHIBITOR COMPOUNDS
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The present invention relates to compounds of formula (I), wherein R, R, Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1 - also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them
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Paragraph 00325
(2014/03/26)
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- TETRAZOLE COMPOUNDS AS CALCIUM CHANNEL BLOCKERS
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The present invention relates to novel tetrazole compounds; to processes for their preparation; to pharmaceutical compositions containing the compounds; and to the use of the compounds in therapy to treat diseases for which blocking the Cav2.2 calcium channels is beneficial. Formula (I) wherein A is: (II) or (III)
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Page/Page column 43
(2012/02/01)
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- A remarkably simple N-formylation of anilines using polyethylene glycol
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N-Formylation of anilines has efficiently been carried out at room temperature in excellent yields by treatment with formic acid in polyethylene glycol (PEG-400). No additional solvent and catalyst are required.
- Das, Biswanath,Krishnaiah, Maddeboina,Balasubramanyam,Veeranjaneyulu, Boyapati,Nandan Kumar
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p. 2225 - 2227
(2008/09/18)
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- A HIGHLY EFFICIENT AND GENERAL N-MONOMETHYLATION OF FUNCTIONALIZED PRIMARY AMINES VIA FORMYLATION -- BORANE:METHYL SULFIDE REDUCTION
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Formylation of functionalized primary aromatic and aliphatic amines with acetic formic anhydride (AFA) followed by borane:methyl sulfide reduction in the same pot affords the corresponding N-methylamines in excellent isolated yields, uncontaminated by bis alkylation; the reaction sequence is applicable to even very weakly basic and sterically hindered amines.
- Krishnamurthy, S.
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p. 3315 - 3318
(2007/10/02)
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