36818-07-2Relevant articles and documents
Structure-based design of novel quinoxaline-2-carboxylic acids and analogues as Pim-1 inhibitors
Oyallon, Bruno,Brachet-Botineau, Marie,Logé, Cédric,Bonnet, Pascal,Souab, Mohamed,Robert, Thomas,Ruchaud, Sandrine,Bach, Stéphane,Berthelot, Pascal,Gouilleux, Fabrice,Viaud-Massuard, Marie-Claude,Denevault-Sabourin, Caroline
, p. 101 - 109 (2018)
We identified a new series of quinoxaline-2-carboxylic acid derivatives, targeting the human proviral integration site for Moloney murine leukemia virus-1 (HsPim-1) kinase. Seventeen analogues were synthesized providing useful insight into structure-activity relationships studied. Docking studies realized in the ATP pocket of HsPim-1 are consistent with an unclassical binding mode of these inhibitors. The lead compound 1 was able to block HsPim-1 enzymatic activity at nanomolar concentrations (IC50 of 74 nM), with a good selectivity profile against a panel of mammalian protein kinases. In vitro studies on the human chronic myeloid leukemia cell line KU812 showed an antitumor activity at micromolar concentrations. As a result, compound 1 represents a promising lead for the design of novel anticancer targeted therapies.
Uncatalyzed condensation between aryl-1,2-diamines and diethyl bromomalonate: a one-pot access to substituted ethyl 3-hydroxyquinoxaline-2-carboxylates
Haldar, Pranab,Dutta, Bishnupada,Guin, Joyram,Ray, Jayanta K.
, p. 5855 - 5857 (2007)
A one-pot method for the synthesis of substituted ethyl 3-hydroxyquinoxaline-2-carboxylates under solvent and catalyst free conditions has been developed.
A highly selective fluorescent chemosensor for Mg2+ based on a diarylethene with a quinoxaline unit
Zhang, Yaping,Li, Hui,Jiang, Duohua,Pu, Shouzhi
, (2020)
A new fluorescent probe 1O was synthesized through linking diarylethene and Quinoxaline-2-hydraqzide group, probe 1O showed a selective “off-on” fluorescent response toward Mg2+. In the presence of Mg2+, the probe 1O displayed a distinct change of fluorescence color, from dark to green, the fluorescence intensity increased 6.8-fold, and meanwhile, emission peak has a significant blue shift, which was shifted from 524 nm to 518 nm. Then, on account of the fluorescence properties of compound 1O, we designed a logic gate. On top of that, probe 1O also can be successfully used to monitor Mg2+ of the actual water samples.
Identification of 3-(benzazol-2-yl)quinoxaline derivatives as potent anticancer compounds: Privileged structure-based design, synthesis, and bioactive evaluation in vitro and in vivo
Liu, Qing-Qing,Lu, Ke,Zhu, Hai-Miao,Kong, Shi-Lin,Yuan, Jing-Mei,Zhang, Guo-Hai,Chen, Nan-Ying,Gu, Chen-Xi,Pan, Cheng-Xue,Mo, Dong-Liang,Su, Gui-Fa
, p. 293 - 308 (2019)
Inspired by the common structural characteristics of numerous known antitumor compounds targeting DNA or topoisomerase I, 3-(benzazol-2-yl)-quinoxaline-based scaffold was designed via the combination of two important privileged structure units —quinoxaline and benzazole. Thirty novel 3-(benzazol-2-yl)-quinoxaline derivatives were synthesized and evaluated for their biological activities. The MTT assay indicated that most compounds possessed moderate to potent antiproliferation effects against MGC-803, HepG2, A549, HeLa, T-24 and WI-38 cell lines. 3-(Benzoxazol- -2-yl)-2-(N-3-dimethylaminopropyl)aminoquinoxaline (12a) exhibited the most potent cytotoxicity, with IC50 values ranging from 1.49 to 10.99 μM against the five tested cancer and one normal cell line. Agarose-gel electrophoresis assays suggested that 12a did not interact with intact DNA, but rather it strongly inhibited topoisomerase I (Topo I) via Topo I-mediated DNA unwinding to exert its anticancer activity. The molecular modeling study indicated that 12a adopt a unique mode to interact with DNA and Topo I. Detailed biological study of 12a in MGC-803 cells revealed that 12a could arrest the cell cycle in G2 phase, inducing the generation of reactive oxygen species (ROS), the fluctuation of intracellular Ca2+, and the loss of mitochondrial membrane potential (ΔΨm). Western Blot analysis indicated that 12a-treatment could significantly up-regulate the levels of pro-apoptosis proteins Bak, Bax, and Bim, down-regulate anti-apoptosis proteins Bcl-2 and Bcl-xl, and increase levels of cyclin B1 and CDKs inhibitor p21, cytochrome c, caspase-3, caspase-9 and their activated form in MGC-803 cells in a dose-dependent manner to induce cell apoptosis via a caspase-dependent intrinsic mitochondria-mediated pathway. Studies in MGC-803 xenograft tumors models demonstrated that 12a could signi?cantly reduce tumor growth in vivo at doses as low as 6 mg/kg with low toxicity. Its convenient preparation and potent anticancer efficacy in vivo makes the 3-(benzazol-2-yl)quinoxaline scaffold a promising new chemistry entity for the development of novel chemotherapeutic agents.
3-Arylamino-quinoxaline-2-carboxamides inhibit the PI3K/Akt/mTOR signaling pathways to activate P53 and induce apoptosis
Chen, Nan-Ying,Lu, Ke,Yuan, Jing-Mei,Li, Xiao-Juan,Gu, Zi-Yu,Pan, Cheng-Xue,Mo, Dong-Liang,Su, Gui-Fa
, (2021/06/30)
Thirty-eight new 3-arylaminoquinoxaline-2-carboxamide derivatives were in silico designed, synthesized and their cytotoxicity against five human cancer cell lines and one normal cells WI-38 were evaluated. Molecular mechanism studies indicated that N-(3-A
Synthesis, EGFR-TK inhibition and anticancer activity of new quinoxaline derivatives
Ahmed, Eman A.,Mohamed, Mamdouh F. A.,Omran, Ahmed,Salah, Hanan
supporting information, p. 2924 - 2940 (2020/07/13)
Ethyl 4-substituted-3-oxo-quinoxaline-2-carboxylates 3–5 were obtained via alkylation of ethyl 3-oxo-3,4-dihydroquinoxaline-2-carboxylate (1). Compound 1 was heterocyclized using hydrazines, ethylenediamine, and ethanolamine to give pyrazoloquinoxalines 6, 7, diazepinoquinoxaline 8, and oxazepinoquinoxaline 10. The quinoxaline-2-carboxamides 9, 11, 12 were prepared via condensation of compound 1 with different amines. Compound 1 was thiated using Lawesson’s reagent affording quinoxaline-3-thione 13, in fair yield. In addition, the reaction of 4-methyl-3-oxoquinoxaline 3 with some binucleophiles led to a series of new oxoquinoxaline derivatives 14–18. The molecular structure of compounds 1, 3, and 9 was confirmed by X-ray crystallography. The anti-proliferative activity showed that among all the tested compounds, compounds 3, (IC50 2.51 ± 3.0, 4.22 ± 1.6 and 2.27 ± 1.9 μM), 11 (IC50 1.32 ± 2.61, 1.41 ± 1.23 and 1.18 ± 1.91 μM) and 17 (IC50 1.72 ± 1.32, 1.85 ± 0.94 and 1.92 ± 4.83 μM) showed noteworthy anti-proliferative effects against the three cancer cell lines, HCT116, HePG2 and MCF7, respectively, compared to the reference drugs doxorubicin (IC50 1.41 ± 0.58, 0.90 ± 0.62 and 1.01 ± 3.02 μM) and erlotinib (IC50 1.63 ± 0.81, 1.57 ± 0.62 and 1.49 ± 0.54 μM). Compounds 3 (0.899 nM), 11 (0.508 nM) and 17 (0.807) showed strong EGFR inhibitory activity compared to Erlotinib (0.439 nM) and these results are in agreement with the docking study. These results suggest that compounds could probably be promising anticancer agents with EGFR inhibitory activity.
2-(omega-dialkylamino)aminoalkyl-3-aryloxazolequinoxaline compounds as well as preparation method and application thereof
-
Paragraph 0060; 0061; 0062, (2018/09/26)
The invention discloses 2-(omega-dialkylamino)aminoalkyl-3-aryloxazolequinoxaline compounds as well as a preparation method and application thereof, and specially relates to a pharmaceutical composition containing the compounds, and an application in preparation of antitumor and topoisomerase I inhibiting drugs. The compounds disclosed by the invention have a good inhibitory effect on topoisomerase I, and exhibit good antitumor effects in vitro and in vivo.
Synthesis of 2-(Quinoxalin-2-ylamino-benzotriazolyl) Pentanedioic Derivatives as Potential Anti-Folate Agents
Briguglio,Piras,Corona,Pirisi,Burrai,Boatto,Gavini,Rassu
, p. 1721 - 1737 (2016/11/23)
Anti-folate agents had a significant impact on therapeutic treatment plans for diseases such as cancer, and bacterial and parasitic infections, notably malaria. Quinoxaline derivatives showed in vitro anticancer activity and were able to inhibit both the dihydrofolate reductase and thymidylate synthase. Here, we decided to combine the chemical properties of quinoxalines and quinoxaline 1,4-dioxides with those of benzotriazole nucleus with the aim to evaluate the resulting biological properties. Two main new series, including more than 60 compounds, were prepared. In the first one, the benzotriazole moiety was linked through the nitrogen atoms 1, 2, or 3, to a glutaric acid substituent to simulate a glutamic moiety. In the second series, the glutaric acid was substituted with acetic acid moiety to evaluate the effects of steric hindrance. Here, we describe the multistep chemical processes to obtain all titled quinoxalines starting from commercially available diamines. The classical oxidation of selected quinoxalines was unsuccessful, and we have come to an independent synthetic pathway to obtain new derivatives linked to the benzotriazole moieties starting from synthons bearing N-oxide functionality.
Synthesis of multisubstituted dihydroquinoxaline derivatives by tandem N-alkylation and addition reactions of 3-oxoquinoxaline-2-carboxylates
Miyamaru, Satoru,Umezu, Kazuto,Ito, Akinori,Shimizu, Makoto
supporting information, p. 3327 - 3337 (2015/05/20)
This report describes a one-pot synthesis of multisubstituted dihydroquinoxalin-2-ones using an umpolung N-alkylation followed by oxidation and C-alkylation reactions. Moreover, the synthesis of tricyclic compounds containing a dihydroquinoxaline skeleton was carried out by ring closing metathesis (RCM) of the resulting N,C-bis-addition products containing olefins.
Ligand-based design, synthesis, and pharmacological evaluation of 3-methoxyquinoxalin-2-carboxamides as structurally novel serotonin type-3 receptor antagonists
Mahesh, Radhakrishnan,Devadoss, Thangaraj,Dhar, Arghya Kusum,Venkatesh, Sudali Muthu,Mundra, Sourabh,Pandey, Dilip Kumar,Bhatt, Shvetank,Jindal, Ankur Kumar
, p. 687 - 694 (2012/10/29)
Employing a ligand-based approach, 3-methoxyquinoxalin-2-carboxamides were designed as serotonin type-3 (5-HT3) receptor antagonists and synthesized from the starting material o-phenylenediamine in a sequence of reactions. The structures of the
