- Synthesis and antibacterial activity of novel ethyl 2-alkoxyimino-2-benzimidazol-2-yl acetates bearing a morpholine group
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In the search for new benzimidazole derivatives with high antibacterial activity and for which bacterial resistance is low, novel ethyl 2-(alkoxyimino)-2-[1-(4-morpholinocarbonylmethyl)-1H-benzimidazol-2-yl]acetates have been synthesized by multi-step rea
- Zhang, Peizhi,Wan, Fuxian,Li, Ying,Li, Chengkun,Jiang, Lin
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- N,N-Dialkyl-N′-Chlorosulfonyl Chloroformamidines in Heterocyclic Synthesis. Part XIV.Synthesis and Reactivity of the New Benzo[4,5]imidazo[1,2-b][1,2,6]thiadiazine Ring System
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N,N-Dialkyl-N′-chlorosulfonyl chloroformamidines 1 underwent regioselective reactions with the 1,3-NCC bis-nucleophilic 1H-benzimidazole-2-acetonitriles 4 and related compounds to produce benzo[4,5]imidazo[1,2-b][1,2,6]thiadiazine dioxides 6, 9, 12, and 14, representatives of a new ring system. Reaction of dichlorides 1 with trifluoroacetyl derivative 16 afforded benzo[4,5]imidazo[1,2-c]pyrimidines 19 and 20. An N-acyl and some N-alkyl derivatives of benzimidazo-thiadiazines 6 were prepared to demonstrate the potential of this new ring system as a novel scaffold for synthetic and medicinal chemistry applications. Treatment of the 4-cyano-5-methyl-benzimidazo-thiadiazine 26c with LiAlH4 resulted in an unexpected and remarkable conversion of the nitrile to give the 4,5-dimethyl-benzimidazo-thiadiazine 29.
- Innes, Dylan,Perkins, Michael V.,Liepa, Andris J.,Francis, Craig L.
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- Composition based on benzimidazole carboxylic acid compound and application thereof
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The invention belongs to the field of medicine and pharmacology, and particularly relates to a pharmaceutical composition taking benzimidazole carboxylic acid and pharmaceutically acceptable salt thereof as active ingredients. The pharmaceutical composition taking the benzimidazole carboxylic acid and pharmaceutically acceptable salt thereof as main active ingredients is used for preventing and/ortreating respiratory tract reaction and nasal congestion caused by allergic reaction, nasal congestion caused by other reasons and other symptoms, and can realize immediate and/or lasting alleviationof congestion. The invention also provides a method of treating and/or alleviating and/or preventing nasal congestion in a patient, the method comprising administering to a patient in need thereof aneffective amount of the pharmaceutical composition of the benzimidazole carboxylic acid or a pharmaceutically acceptable salt thereof.
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- The uses of ethyl 2-(1H-benzo[D]imidazol-2-yl)acetate to synthesis pyrazole, thiophene, pyridine and coumarin derivatives with antitumor activities
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In the present work, the ethyl 2-(1H-benzo[d]imidazol-2-yl)acetate (3) was subjected to a series of heterocyclization reactions through its reaction with different chemical reagents. The resulting molecules were thiophene, pyrazole, coumarin derivatives incorporated benzo[d]imidazole moiety. All the synthesized compounds were determined by elemental analysis, 1H NMR, 13C NMR, and MS. The antitumor evaluations of the newly synthesized products toward the three cancer cell lines MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), and SF-268 (CNS cancer) showed that compounds 5a, 9b, 9c, 17, 23b and 38 were of the highest potencies among the synthesized compounds.
- Mohareb, Rafat M.,Gamaan, Marwa S.
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p. 541 - 557
(2018/12/13)
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- Design, synthesis, docking and QSAR study of substituted benzimidazole linked oxadiazole as cytotoxic agents, EGFR and erbB2 receptor inhibitors
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The synthesis of benzimidazole linked oxadiazole derivatives designed as potential EGFR and erbB2 receptor inhibitors with anticancer and apoptotic activity were studied. Compounds 7a specifically inhibit EGFR and erbB2 receptor at 0.081 and 0.098 μM concentration. Some of the compounds showed strong, broad-spectrum antiproliferative activitiy when tested against five human cancer cell lines. Compounds 7a and 7n were more cytotoxic than 5-fluorouracil against MCF-7 cancer cell, with IC50values of 5.0 and 2.55 μM whereas, only 7a led to cell cycle arrest at G2/M phase accompanied by an increase in apoptosis. Compounds 7a and 7n showed normal architecture of myofibrils in cardiomyopathy study whereas only compound 7a showed nearly equal biochemical parameters (SGOT and SGPT) when compared to control. Molecular docking & 3D-QSAR studies were used to establish interactions of 7a and 7n within the active site of enzyme for ATP binding site of kinase domain.
- Akhtar, Md Jawaid,Siddiqui, Anees Ahmad,Khan, Ahsan Ahmed,Ali, Zulphikar,Dewangan, Rikeshwer Prasad,Pasha, Santosh,Yar, M. Shahar
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p. 853 - 869
(2016/12/22)
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- Discovery and Optimization of Small Molecule Splicing Modifiers of Survival Motor Neuron 2 as a Treatment for Spinal Muscular Atrophy
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The underlying cause of spinal muscular atrophy (SMA) is a deficiency of the survival motor neuron (SMN) protein. Starting from hits identified in a high-throughput screening campaign and through structure-activity relationship investigations, we have developed small molecules that potently shift the alternative splicing of the SMN2 exon 7, resulting in increased production of the full-length SMN mRNA and protein. Three novel chemical series, represented by compounds 9, 14, and 20, have been optimized to increase the level of SMN protein by >50% in SMA patient-derived fibroblasts at concentrations of 160 nM. Daily administration of these compounds to severe SMA Δ7 mice results in an increased production of SMN protein in disease-relevant tissues and a significant increase in median survival time in a dose-dependent manner. Our work supports the development of an orally administered small molecule for the treatment of patients with SMA.
- Woll, Matthew G.,Qi, Hongyan,Turpoff, Anthony,Zhang, Nanjing,Zhang, Xiaoyan,Chen, Guangming,Li, Chunshi,Huang, Song,Yang, Tianle,Moon, Young-Choon,Lee, Chang-Sun,Choi, Soongyu,Almstead, Neil G.,Naryshkin, Nikolai A.,Dakka, Amal,Narasimhan, Jana,Gabbeta, Vijayalakshmi,Welch, Ellen,Zhao, Xin,Risher, Nicole,Sheedy, Josephine,Weetall, Marla,Karp, Gary M.
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supporting information
p. 6070 - 6085
(2016/07/26)
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- NOVEL COMPOSITIONS, USES AND METHODS FOR MAKING THEM
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Generally, the present invention provides novel quinolone compounds and pharmaceutical composition thereof which may inhibit cell proliferation and/or induce cell apoptosis. The present invention also provides methods of preparing such compounds and compositions, and methods of making and using the same.
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Paragraph 0294
(2015/11/27)
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- New synthesis of 2-benzimidazoleacetates and study of their Knoevenagel reaction
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To obtain 2-benzimidazolyl acrylate 2, a new efficient synthesis of 2-benzimidazoleacetate, involving esterification of 2-benzimidazole acetic acid at low temperature as the crucial step, was developed. The generality and efficiency of the process was illustrated by the high-yield synthesis of methyl, ethyl, i-propyl, and n-butyl 2-benzimidazoleacetate. The Knoevenagel reaction of 2-benzimidazoleacetate with aromatic aldehydes was studied. It was found that only in the presence of a catalytic amount of morpholine could the Knoevenagel reaction proceed to give the expected 3-aryl-2-benzimidazolyl acrylate. A mechanism for the morpholinecatalyzed reaction is suggested. Springer Science+Business Media B.V. 2011.
- Yang, Peng Hui,Zhang, Qun Zheng,Yu, Hong Jiang
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p. 1403 - 1409
(2012/11/07)
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- SUBSTITUTED HYDRAZIDE COMPOUNDS AND USE THEREOF
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The invention relates to substituted hydrazide compounds as shown by general formula I, including geometrical isomers, pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, and use of the same, wherein the substitutents Ar and R have the same meanings as given in the Description. The invention further relates to the use of compounds of general formula I in the preparation of medicament for the treatment and/or prevention of cancer and other proliferative diseases.
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- SUBSTITUTED HYDRAZIDE COMPOUNDS AND APPLICATION THEREOF
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The invention relates to substituted hydrazide compounds as shown by general formula I, including geometrical isomers, pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, and use of the same, wherein the substitutents Ar and R having the same meanings as given in the Description. T The invention further relates to the use of compounds of general formula I in the preparation of medicament for the treatment and/or prevention of cancer and other proliferative diseases.
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- A SAR study of novel antiproliferative ruthenium and osmium complexes with quinoxalinone ligands in human cancer cell lines
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A series of ruthenium(II) arene complexes with 3-(1H-benzimidazol-2-yl)-1H- quinoxalin-2-one, bearing pharmacophoric groups of known protein kinase inhibitors, and related benzoxazole and benzothiazole derivatives have been synthesized. In addition, the corresponding osmium complexes of the unsubstituted ligands have also been prepared. The compounds have been characterized by NMR, UV-vis, and IR spectroscopy, ESI mass spectrometry, elemental analysis, and by X-ray crystallography. Antiproliferative activity in three human cancer cell lines (A549, CH1, SW480) was determined by MTT assays, yielding IC50 values of 6-60 μM for three unsubstituted metal-free ligands, whereas values for the metal complexes vary in a broad range from 0.3 to 140 μM. Complexation with osmium of quinoxalinone derivatives with benzimidazole or benzothiazole results in a more consistent increase in cytotoxicity than complexation with ruthenium. For selected compounds, the capacity to induce apoptosis was confirmed by fluorescence microscopy and flow-cytometric analysis, whereas cell cycle effects are only moderate.
- Ginzinger, Werner,Mühlgassner, Gerhard,Arion, Vladimir B.,Jakupec, Michael A.,Roller, Alexander,Galanski, Markus,Reithofer, Michael,Berger, Walter,Keppler, Bernhard K.
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p. 3398 - 3413
(2012/06/04)
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- Combination therapy with CHK1 inhibitors
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Compounds of Structure I, and salts, tautomers, stereoisomers, and mixtures thereof may be used in methods of inhibiting checkpoint kinase 1 in subjects, in methods for inducing cell cycle progression, and in methods for increasing apoptosis in cells. Such compounds may be used to prepare pharmaceutical compositions and may be used in conjunction with DNA damaging agents.
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- Inhibition of FGFR3 and treatment of multiple myeloma
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Methods of inhibiting fibroblast growth factor receptor 3 and treating various conditions mediated by fibroblast growth factor receptor 3 are provided that include administering to a subject a compound of Structure I, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I have the following structure where and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting fibroblast growth factor receptor 3 and for use in treating conditions mediated by fibroblast growth factor receptor 3 such as multiple myeloma.
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- BENZIMIDAZOLE QUINOLINONES AND USES THEREOF
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Methods of inhibiting various enzymes and treating various conditions are provided that include administering to a subject a compound of Structure I or IB, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I and IB have the following structures and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting various enzymes and for use in treating conditions mediated by such enzymes.
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- Quinolinone derivatives
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Organic compounds having the formulas I and II are provided where the variables have the values described herein. Pharmaceutical formulations include the organic compounds or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier and may be prepared by mixing the organic compounds or pharmaceutically acceptable salts of the organic compounds with a carrier and water. A method of treating a patient includes administering a pharmaceutical formulation according to the invention to a patient in need thereof.
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- Heterocyclic compounds
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Organic compounds having the structural formulas I, II, and III are provided where the variables have the values described herein and R1 and R2 in structure I join together to form a 5 to 7 membered substituted or unsubstituted ring including at least one O, N, or S atom, and Z is an O, S, NH or NR group in structures I and II. Pharmaceutical formulations include the organic compound or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. A method of treating a patient includes administering a pharmaceutical formulation according to the invention to a patient in need thereof.
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- Quinolinone derivatives
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Organic compounds having the formulas I and II are provided where the variables have the values described herein. Pharmaceutical formulations include the organic compounds or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier and may be prepared by mixing the organic compounds or pharmaceutically acceptable salts of the organic compounds with a carrier and water. A method of treating a patient includes administering a pharmaceutical formulation according to the invention to a patient in need thereof.
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- Synthesis and photochromic properties of 2-(3-nitro-2-pyridylmethyl)benzazoles
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2-(3-Nitro-2-pyridylmethyl)benzazoles were synthesized, and their photochromic properties were studied by flash photolysis. Introduction of a nitropyridyl instead of the nitrophenyl moiety into the 2-methyl group insignificantly increases the basicity of the methylene group. Nitropyridyl-substituted benzazoles give rise to three detectable photoinduced forms: the corresponding union at pH > 10, azamerocyanine at pH ≈ 4, and monomethinecyanine at pH ≈ 1. Irradiation of solutions of weakly basic henzoxazole and benzothiazole derivatives at pH ≈ 4 results in formation of neutral chelate structures in which the hydrogen atom is linked simultaneously to two nitrogen atoms: one in the pyridine ring, and the second, in the azole ring.
- Zakhs,Ponyaev,Subbotina,El'tsov
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p. 1076 - 1087
(2007/10/03)
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- SYNTHESIS AND APPLICATION OF IMIDAZOLE DERIVATIVES. SYNTHESIS OF PYRIDOBENZIMIDAZOLONE DERIVATIVES
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Pyrido>benzimidazole derivatives (12a and 19a) were synthesized in moderate yields via an intramolecular aldol-condensation of 2-acetyl-1-formylbenzimidazole (11) and an intramolecular acylation of the acylimidazolide (18) prepared from 2-ethoxycarbonylmethyl-1-(2-carboxyethyl)benzimidazole (17), respectively.
- Ohta, Shunsaku,Yuasa, Teruyuki,Narita, Yoshihiro,Kawasaki, Ikuo,Minamii, Eiji,Yamashita, Masayuki
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p. 1923 - 1931
(2007/10/02)
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