84955-31-7Relevant academic research and scientific papers
Design, synthesis and in vitro apoptotic mechanism of novel pyrrolopyrimidine derivatives
Kilic-Kurt, Zühal,Bakar-Ates, Filiz,Aka, Yeliz,Kutuk, Ozgur
, p. 511 - 519 (2019)
In this work we described the synthesis and evaluation of cytotoxic and apoptotic activity of novel pyrrolopyrimidine derivatives against A549, PC3 and MCF-7 cells. Among the synthesized compounds, 6b, 8a, 9a and 7a, 8b displayed the significant cytotoxic
Novel pyrrolopyrimidine derivatives induce p53-independent apoptosis via the mitochondrial pathway in colon cancer cells
Aka, Yeliz,Kilic-Kurt, Zühal,Kutuk, Ozgur
, (2020)
A series of novel pyrrolopyrimidine urea derivatives were synthesized and evaluated for their anticancer activity against colon cancer cell lines. Compounds showed the remarkable cytotoxic activity on HCT-116 wt cell line. The most potent compound 4c (IC50 = 0.14 μM) induced apoptosis in HCT-116 wt and HCT-116 p53?/? cell lines. Otherwise, treatment of HCT-116 BAX?/?BAK?/? cells with compound 4c didn't lead to activation of apoptosis, suggesting that compound 4c induces apoptotic cell death by activating BAX/BAK-dependent pathway. Moreover, while the compound 4c increase the activation of caspase-3 and caspase-9 levels in HCT-116 wt and HCT-116 p53?/? cells, caspase-3 or caspase-9 activation was not observed in HCT-116 BAX?/?BAK?/? cells. In addition, compound 4c induced mitochondrial apoptosis in cells grown as oncospheroids, which better mimic the in vivo milieu of tumors. 4c treatment also activated JNK along with inhibition of prosurvival kinases such as Akt and ERK 1/2 in HCT-116 wt and HCT-116 p53 ?/? cells as well as in HCT-116 BAX?/?BAK?/? cells. Notably, our results indicated that compound 4c induced mitochondrial apoptosis through activation p53-independent apoptotic signaling pathways.
Synthesis of Galactosyl-Queuosine and Distribution of Hypermodified Q-Nucleosides in Mouse Tissues
Carell, Thomas,Ensfelder, Timm T.,Heiss, Matthias,Hillmeier, Markus,Kellner, Stefanie,Müller, Markus,Michalakis, Stylianos,Sch?n, Alexander,Scheel, Constanze,Thumbs, Peter,Wagner, Mirko
supporting information, p. 12352 - 12356 (2020/04/27)
Queuosine (Q) is a hypermodified RNA nucleoside that is found in tRNAHis, tRNAAsn, tRNATyr, and tRNAAsp. It is located at the wobble position of the tRNA anticodon loop, where it can interact with U as well as C bases located at the respective position of the corresponding mRNA codons. In tRNATyr and tRNAAsp of higher eukaryotes, including humans, the Q base is for yet unknown reasons further modified by the addition of a galactose and a mannose sugar, respectively. The reason for this additional modification, and how the sugar modification is orchestrated with Q formation and insertion, is unknown. Here, we report a total synthesis of the hypermodified nucleoside galactosyl-queuosine (galQ). The availability of the compound enabled us to study the absolute levels of the Q-family nucleosides in six different organs of newborn and adult mice, and also in human cytosolic tRNA. Our synthesis now paves the way to a more detailed analysis of the biological function of the Q-nucleoside family.
Preparation method for catalyzing pyrimidine cyclic hydroxyl chlorination by tetraethylammonium chloride
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Paragraph 0026-0028, (2020/04/17)
The invention discloses a preparation method for catalyzing pyrimidine cyclic hydroxyl chlorination by tetraethylammonium chloride, which comprises the following steps: (1) adding phosphorus oxychloride into a container, adding tetraethylammonium chloride as a catalyst, adding a pyrimidine cyclic hydroxyl compound, and heating to react; (2) preparing an alkali liquor, cooling to 0 DEG C, and slowly dropwise adding an obtained reaction liquid into the alkali liquor for quenching to obtain a target product. The method has the advantages that the provided pyrimidine cyclic hydroxyl chlorination catalysis method is small in environmental pollution, the obtained product is light in color, the catalysis efficiency is high, and the phosphorus oxychloride recovery pressure is small.
Nucleoside heterocycle that binds to both thymidine and cytidine
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Page/Page column 4; 5, (2018/09/14)
This application discloses nucleoside analogs that when incorporated into a oligonucleotide, forms a nucleobase pair with either thymidine or cytidine that are present in a complementary strand at the paired position. These analogs are called “purine bive
7-to nitrogen-7-halogen-guanine nucleoside synthesis method
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Paragraph 0048; 0049; 0050, (2016/10/08)
The invention discloses a method for synthesizing 7-denitrification-7-halogen guanosine. The method comprises the following steps: removing a protecting group of a compound of the formula (III) under an alkali condition so as to obtain a compound of the f
An improved synthesis approach of the HIV-1 inhibitor RDEA427, a pyrrolo[2,3-d]pyrimidine derivative
Huang, Boshi,Liu, Xinhao,Li, Wanzhuo,Chen, Zihui,Kang, Dongwei,Zhan, Peng,Liu, Xinyong
, p. 45 - 51 (2017/01/29)
The diarylpyrimidine-like derivative RDEA427 is a highly potent inhibitor against wild-type and a wide range of drug-resistant HIV-1 strains and has attracted much attention. However, the yield of its reported synthesis is too low and the route is less environment-friendly and uneconomic. In order to achieve a short and more economic synthesis of RDEA427, an investigation was carried out. The optimized synthesis approach of RDEA427 was accomplished in an increased overall yield (39%). Moreover, the new route is more environment-friendly and economic. This work will accelerate the drug discovery process.
Discovery of Potent and Selective Leads against Toxoplasma gondii Dihydrofolate Reductase via Structure-Based Design
Welsch, Matthew E.,Zhou, Jian,Gao, Yueqiang,Yan, Yunqing,Porter, Gene,Agnihotri, Gautam,Li, Yingjie,Lu, Henry,Chen, Zhongguo,Thomas, Stephen B.
supporting information, p. 1124 - 1129 (2016/12/16)
Current treatment of toxoplasmosis targets the parasite’s folate metabolism through inhibition of dihydrofolate reductase (DHFR). The most widely used DHFR antagonist, pyrimethamine, was introduced over 60 years ago and is associated with toxicity that can be largely attributed to a similar affinity for parasite and human DHFR. Computational analysis of biochemical differences between Toxoplasma gondii and human DHFR enabled the design of inhibitors with both improved potency and selectivity. The approach described herein yielded TRC-19, a promising lead with an IC50 of 9 nM and 89-fold selectivity in favor of Toxoplasma gondii DHFR, as well as crystallographic data to substantiate in silico methodology. Overall, 50% of synthesized in silico designs met hit threshold criteria of IC50 2-fold selectivity favoring Toxoplasma gondii, further demonstrating the efficiency of our structure-based drug design approach.
IRAK INHIBITORS AND USES THEREOF
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Paragraph 00252; 00255; 00256, (2014/02/15)
The present invention provides furano- and pyrrolo- pyrimidine and pyridine compounds, compositions thereof, and methods of using the same.
Synthesis and evaluation against hepatitis C virus of 7-deaza analogues of 2′-C-methyl-6-O-methyl guanosine nucleoside and l-Alanine ester phosphoramidates
Bourdin, Claire,McGuigan, Christopher,Brancale, Andrea,Chamberlain, Stanley,Vernachio, John,Hutchins, Jeff,Gorovits, Elena,Kolykhalov, Alexander,Muhammad, Jerry,Patti, Joseph,Henson, Geoffrey,Bleiman, Blair,Bryant, K. Dawn,Ganguly, Babita,Hunley, Damound,Obikhod, Aleksandr,Walters, C. Robin,Wang, Jin,Ramamurty, Changalvala V.S.,Battina, Srinivas K.,Srivinas Rao
supporting information, p. 2260 - 2264 (2013/04/23)
7-Deazapurines are known to possess broad antiviral activity, however the 2′-C-methylguanosine analogue displays poor cell permeation and limited phosphorylation, thus is not an efficient inhibitor of hepatitis C virus (HCV) replication. We previously rep
