- Synthesis and cytotoxic activity of chalcone analogues containing a thieno[2,3-d]pyrimidin-2-yl group as the A-ring or B-ring
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Many natural or synthetic chalcones have potential anti-tumor activity. Here, we synthesized two series of chalcone analogues containing a thieno[2,3-d]pyrimidin-2-yl group and evaluated for their cytotoxic activity towards cultured human lung cancer A549 and colorectal HCT-116 cells. Among them, compound 8d was the most cytotoxic against HCT-116 cells, with an IC50 value of 2.65 μM. Analyses of the phenotypic changes induced by this compound found a dose-dependent accumulation of HCT-116 cells in sub-G1 phase, indicating that compound 8d might induce apoptosis. Furthermore, we found that 8d triggered mitochondrial membrane potential depolarization, promoted reactive oxygen species formation in HCT-116 cells, and increased the percentage of early and late apoptotic cells. Finally, immunoblotting indicated that 8d increased PARP-1 and caspases 3, 7 and 9 cleavage. These data suggest that compound 8d induces apoptosis via the mitochondrial death pathway.
- Wang, Fu-Cheng,Peng, Bin,Cao, Sheng-Li,Li, Hong-Yun,Yuan, Xiao-Li,Zhang, Ting-Ting,Shi, Ruifeng,Li, Zhuqing,Liao, Ji,Wang, Hailong,Li, Jing,Xu, Xingzhi
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- Synthesis of Tetrasubstituted Thiophenes via Direct Metalation
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Thiophene moiety can be derivatized by various synthetic procedures. The most convenient method seems to be derivatization via direct metalation, but synthesis of polysubstituted thiophenes bearing reactive groups is difficult because of high reactivity of organometallic reagents. This work reports the preparation of complex heterocyclic compounds using direct metalation of thiophenes with various reagents (Knochel-Hauser bases, LDA) as an efficient synthetic tool.
- Skácel, Jan,Dra?ínsky, Martin,Janeba, Zlatko
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p. 788 - 797
(2020/02/04)
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- Chalcone analogue containing thieno[2,3-d]pyrimidine-2-yl, preparation method and uses thereof
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The invention discloses a chalcone analogue containing thieno[2,3-d]pyrimidine-2-yl, wherein the chalcone analogue is represented by a general formula (I), and various substituents are defined in thespecification. The invention further discloses a preparation method of the compound. According to the present invention, the compound represented by the general formula (I) has inhibiting effects on the proliferation of human breast cancer cell lines (MFC-7 and MDA-MB-231), human cervical cancer cell lines (HeLa), human colon cancer cell lines (HCT-116 and HT-29) and human lung cancer cell lines (A549), has inhibiting effect on the proliferation of human hepatoma cell lines (HepG2), and can be used as an antitumor drug.
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Paragraph 0159-0161
(2020/01/03)
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- Synthesis, cytotoxic evaluation and target identification of thieno[2,3-d]pyrimidine derivatives with a dithiocarbamate side chain at C2 position
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Two series of thieno[2,3-d]pyrimidine derivatives bearing a dithiocarbamate side chain at the C2 position were synthesized and evaluated for cytotoxic activity in human lung cancer A549 and colon cancer HCT-116 cell lines. Compound 3n exhibited the most cytotoxic effect on A549 cells with an IC50 value of 4.87 μM, inducing a cell cycle arrest at G2/M phase and activating the spindle assembly checkpoint (SAC). To identify the target protein(s) of 3n, we incorporated biotin with 3n through a three-carbon chain and an amide bond to synthesize probe 10. The targeted proteins were pulled down from the A549 total cell lysate by biotin-streptavidin affinity purification and analyzed by mass spectrometry. Tubulin was the only protein identified, which is related to the SAC and directly binds to probe 10 both in vivo and in vitro. Furthermore, compound 3n inhibited tubulin polymerization in vitro in a dose-dependent manner, competed with taxol in binding to tubulin, exerting cytotoxic activity toward taxol-resistant A549 cells. These results demonstrate that thieno[2,3-d]pyrimidine derivative 3n exhibits cytotoxicity in cancer cells by targeting tubulin to activate the SAC and potentially acts as a therapeutic lead compound for taxol-resistant cancers.
- Yang, Chao-Rui,Peng, Bin,Cao, Sheng-Li,Ren, Ting-Ting,Jiang, Wei,Wang, Fu-Cheng,Li, You-Shan,Wang, Guo,Li, Zheng,Xu, Shibin,Liao, Ji,Wang, Hailong,Li, Jing,Xu, Xingzhi
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p. 324 - 340
(2018/05/29)
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- THIENOPYRIMIDINE DERIVATIVE AND USE THEREOF
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The present invention relates to a novel thienopyrimidine derivative and a use thereof, and more particularly, to a novel thienopyrimidine derivative compound and a composition for preventing or treating cancer comprising the same. The compound of the present invention can be effectively used for treating cancer with high FLT3 inhibitory activity and safety. In particular, the compound of the present invention has excellent solubility in physiological salt solutions including water, and thus can be more effectively used for development of therapeutic agents for cancer.COPYRIGHT KIPO 2018
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Paragraph 0117-0118
(2018/09/02)
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- SUBSTITUTED BICYCLIC HETEROCYCLIC COMPOUNDS AS NADPH OXIDASE INHIBITORS
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The present application relates to substituted fused heteroaryl and heterocyclic compounds, useful as nicotinamide adenine dinucleotide phosphate oxidase inhibitors (NADPH oxidase inhibitors), processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment or prevention of various diseases, conditions and/or disorders mediated by NADPH oxidase. (Formula I)
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Page/Page column 109
(2018/12/03)
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- A green chemical approach: a straightforward one-pot synthesis of 2-aminothiophene derivatives via Gewald reaction in deep eutectic solvents
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Abstract: The synergic effect of choline chloride/urea as a deep eutectic solvent was investigated in the synthesis of 2-aminothiophene derivatives via a three-component cyclocondensation of a ketone or an aldehyde with activated nitriles and elemental sulfur catalyzed by NaOH as cheap and highly accessible base. The advantages of this catalytic protocol are eco-friendly, easy to set up, reusability, and a simple separation and purification of products without using chromatography in high yields at short times. Graphical abstract: [Figure not available: see fulltext.]
- Shaabani, Ahmad,Hooshmand, Seyyed Emad,Afaridoun, Hadi
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p. 711 - 716
(2017/03/17)
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- THIENOPYRIMIDINONE NMDA RECEPTOR MODULATORS AND USES THEREOF
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Disclosed herein, in part, are heteroaromatic compounds and methods of use in treating neuropsychiatric disorders, e.g., schizophrenia and major depressive disorder. Pharmaceutical compositions and methods of making heteroaromatic compounds are provided.
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Paragraph 00123-00124
(2017/07/13)
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- Structural modifications at the 6-position of thieno[2,3- d ]pyrimidines and their effects on potency at FLT3 for treatment of acute myeloid leukemia
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Fms-like tyrosine kinase 3 (FLT3) is a well-known and important target for the treatment of acute myeloid leukemia (AML). A series of thieno[2,3-d]pyrimidine derivatives from a modification at the 6-position were synthesized to identify effective FLT3 inhibitors. Although compounds 1 and 2 emerged as promising FLT3 inhibitors among the synthesized compounds, both compounds exhibited poor metabolic stability in human and rat liver microsomes. Hence, further optimization was required for the discovery of FLT3 inhibitors, with a focus on improving metabolic stability. Compound 16d, which had structural modifications of the methyl group at the 5-position and the 4-(2-methylaminoethoxy) phenyl group at the 6-position, exhibited good inhibitory activity against FLT3 and showed effective antiproliferative activity against four leukemia cell lines, including MV4-11. Moreover, compound 16d displayed enhanced metabolic stability. The results of this study indicated that 16d could be a promising compound for further optimization and development as a potent FLT3 inhibitor.
- Kim, Hyuntae,Lee, Chulho,Yang, Jee Sun,Choi, Seonghwi,Park, Chun-Ho,Kang, Jong Soon,Oh, Soo Jin,Yun, Jieun,Kim, Myung-Hwa,Han, Gyoonhee
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- Design and synthesis of novel protein kinase CK2 inhibitors on the base of 4-aminothieno[2,3-d]pyrimidines
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An extension of our previous research work has resulted in a number of new ATP-competitive CK2 inhibitors that have been identified among 4-aminothieno[2,3-d]pyrimidine derivatives. The most active compounds obtained in the course of the research are 3-(5-p-tolyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5e (NHTP23, IC50 = 0.01 μM), 3-(5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5g (NHTP25, IC50 = 0.065 μM) and 3-(6-methyl-5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5n (NHTP33, IC50 = 0.008 μM). Structure-activity relationships of the tested 4-aminothieno[2,3-d]pyrimidine derivatives have been studied and their binding mode with ATP-acceptor site of CK2 has been proposed. A negative effect of intramolecular hydrogen bonding in the compounds' structure is discussed.
- Ostrynska, Olga V.,Balanda, Anatoliy O.,Bdzhola, Volodymyr G.,Golub, Andriy G.,Kotey, Igor M.,Kukharenko, Olexander P.,Gryshchenko, Andrii A.,Briukhovetska, Nadiia V.,Yarmoluk, Sergiy M.
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p. 148 - 160
(2016/04/05)
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- 6,5-BICYCLIC OCTAHYDROPYRROLOPYRIDINE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to 6,5-bicyclic octahydropyrrolopyridine compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 37; 38
(2016/07/05)
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- ETHYLDIAMINE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to ethyldiamne compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 39
(2016/07/05)
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- OXAZOLE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the oxazole compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 40; 41
(2015/02/25)
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- OXAZOLE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the oxazole compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 35
(2015/02/25)
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- Efficient three-component Gewald reactions under Et3N/H 2O conditions
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In a medium consisting of triethylamine and water, methylene ketones undergo room temperature Gewald reactions with elemental sulfur and ethyl cyanoacetate (or malononitrile) to yield 2 aminothiophene derivatives efficiently within short time periods. Because of the high polarity of the medium, products precipitate in the reaction mixtures spontaneously. This makes isolation of the products easy by simple filtration and avoids cumbersome chromatographic separations. Mechanistic studies suggest that the reactions proceed via a Knoevenagel condensation pathway(equation presented). 2013
- Abaee, M. Saeed,Cheraghi, Somayeh
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p. 261 - 269
(2014/04/03)
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- KG-60-piperazine as a new heterogeneous catalyst for gewald three-component reaction
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Piperazine supported on amorphous silica (KG-60-piperazine) as a basic catalyst acts in the Gewald three-component reaction of some aldehydes and ketones with malononitrile as well as ethyl cyanoacetate. The catalyst shows general utility with a variety of starting carbonyl compounds. Moreover, the catalyst can be reused for four additional cycles without significant loss of the activity. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
- Rezaei-Seresht, Esmail,Tayebee, Reza,Yasemi, Mohammad
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p. 1859 - 1864
(2013/05/21)
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- IRAK INHIBITORS AND USES THEREOF
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The present invention relates to compounds and methods useful for inhibiting one or more interleukin-l receptor-associated kinases ("IRAK"). In some embodiments, a provided compound inhibits IRAK-1 and IRAK-4. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.
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Page/Page column 209-213
(2012/07/28)
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- Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin- 4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2
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A novel series of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids has been synthesized and tested in vitro towards human protein kinase CK2. It was revealed that the most active compounds inhibiting CK2 are 3-{[5-(4-methylphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid and 3-{[5-(4-ethoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid (IC 50 values are 0.1 μM and 0.125 μM, respectively). Structure-activity relationships of 28 tested thienopyrimidine derivatives have been studied and binding mode of this chemical class has been predicted. Evaluation of the inhibitors on seven protein kinases revealed considerable selectivity towards CK2.
- Golub, Andriy G.,Bdzhola, Volodymyr G.,Briukhovetska, Nadiia V.,Balanda, Anatoliy O.,Kukharenko, Olexander P.,Kotey, Igor M.,Ostrynska, Olga V.,Yarmoluk, Sergiy M.
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experimental part
p. 870 - 876
(2011/04/22)
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- HETEROCYCLIC DERIVATIVES
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The present invention relates to a heterocyclic derivative according to formula I wherein the variables are defined as in the specification, or to a pharmaceutically acceptable salt or solvate thereof. The present invention also relates to a pharmaceutica
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Page/Page column 8
(2009/05/28)
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- Potent dual thymidylate synthase and dihydrofolate reductase inhibitors: Classical and nonclassical 2-amino-4-oxo-5-arylthio-substituted-6- methylthieno[2,3-d]pyrimidine antifolates
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N-{4-[(2-Amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl) sulfanyl]benzoyl}-L-glutamic acid (4) and nine nonclassical analogues 5-13 were synthesized as potential dual thymidylate synthase (TS) and dihydrofolate reductase (DHFR) inhibitors. Th
- Gangjee, Aleem,Qiu, Yibin,Li, Wei,Kisliuk, Roy L.
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experimental part
p. 5789 - 5797
(2009/09/25)
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- Microwave accelerated Gewald reaction: synthesis of 2-aminothiophenes
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Microwave-promoted synthesis of 2-aminothiophenes by multicomponent reactions of a ketone with an active nitrile and elemental sulfur under KF-alumina catalysis is described.
- Sridhar, Madabhushi,Rao, Rayankula Mallikarjuna,Baba, Nanduri H.K.,Kumbhare, Ravindra M.
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p. 3171 - 3172
(2007/10/03)
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- Synthesis of 2-aminothiophenes on ionic liquid phase support using the Gewald reaction
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The first report of the use of task-specific ionic liquid as soluble support for the Gewald synthesis of 2-aminothiophenes is reported in this article. This synthetic method is simple and efficient, and the products are obtained in good to excellent yields with high purities, without the need for chromatographic purification. Copyright Taylor & Francis Group, LLC.
- Hu, Yi,Wei, Ping,Huang, He,Han, Shi-Qing,Ouyang, Ping-Kai
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p. 1543 - 1548
(2007/10/03)
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- Microwave-assisted gewald synthesis of 2-amimothio-phenes using functional ionic liquid as soluble support
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A microwave-assisted liquid-phase Gewald synthesis of 2-aminothiophenes was developed using task-specific ionic liquid - [2-hydemim][BF4] as soluble support. This new synthetic method is simple and efficient, and the products are obtained in good to excellent yields with high purities, without the need for chromatographic purification.
- Hu, Yi,Wei, Ping,Huang, He,Han, Shi-Qing,Ouyang, Ping-Kai
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p. 375 - 380
(2007/10/03)
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- Thienopyridones as AMPK activators for the treatment of diabetes and obesity
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The present invention relates to compounds that activate AMP-activated protein kinase (AMPK), including the preparation of the compounds, compositions containing the compounds and the use of the compounds in the prevention or treatment of disorders such as diabetes, metabolic syndrome, and obesity.
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Page/Page column 47
(2010/02/10)
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- NOVEL HERBICIDES, USAGE THEREOF, NOVEL THIENOPYRIMIDINE DERIVATIVES, INTERMEDIATES OF THE SAME, AND PROCESS FOR PRODUCTION THEREOF
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A herbicide comprising, as an active ingredient, a substituted thienopyrimidine derivative represented by the formula (I): wherein all symbols are defined in the description, a method of using the same, a novel compound useful as the herbicide and a process for producing the same, and an intermediate thereof.
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Page/Page column 53-54
(2010/02/12)
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- Organic reactions in ionic liquids: Gewald synthesis of 2-aminothiophenes catalyzed by ethylenediammonium diacetate
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Ionic liquids based on 1-butyl-3-methylimidazolium tetrafluoroborate (BmimBF4) and 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6) were used as reusable alternatives to volatile organic solvents (VOCs) for ethylenediammonium diacetate (EDDA) catalyzed Gewald synthesis of 2-aminothiophenes. Significant rate enhancement and improvement of the yield were observed. The ionic liquids containing catalyst EDDA were recycled several times with no decreases in yields and reaction rates.
- Hu, Yi,Chen, Zhen-Chu,Le, Zhang-Gao,Zheng, Qin-Guo
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p. 3801 - 3806
(2007/10/03)
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