- Design and synthesis of quinoxaline-1,3,4-oxadiazole hybrid derivatives as potent inhibitors of the anti-apoptotic Bcl-2 protein
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Quinoxaline is one of the privileged heterocyclic fragments for drug molecules. Quinoxaline anticancer drug candidates XK469 and CQS exhibit antiproliferative and proapoptotic properties against various cancers. Based on their chemical structures, we therefore synthesized a series of quinoxaline-1,3,4-oxadiazole hybrids and assessed their anticancer potential on human leukemia HL-60 cells. Although these hybrids exerted significant inhibition of HL-60 cell proliferation, they showed high cytotoxicity on human normal cells (WI-38). Utilizing information from molecular modelling of the hybrids to the anti-apoptotic Bcl-2 protein, we added substructures including phenyl, piperazine, piperidine, and morpholine rings to their frameworks. The designed quinoxaline-1,3,4-oxadiazole hybrid derivatives successfully induced apoptotic response on HL-60 cells with low toxicity on WI-38 cells. Furthermore, RT-PCR analysis demonstrated that these derivatives predominantly inhibit Bcl-2 expression. Our findings highlight the great potential for the development of synthetic quinoxaline-1,3,4-oxadiazole hybrid derivatives as proapoptotic anticancer agents.
- Ono, Yukari,Ninomiya, Masayuki,Kaneko, Daiki,Sonawane, Amol D.,Udagawa, Taro,Tanaka, Kaori,Nishina, Atsuyoshi,Koketsu, Mamoru
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- Organic electroluminescent compound, preparation method thereof and electroluminescent device
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The invention discloses an organic electroluminescent compound. The structural general formula of the organic electroluminescent compound is shown in the specification, and the preparation method of the organic electroluminescent compound comprises the following steps: step 1, adding raw materials A and B into a mixed solvent of THF and deionized water, adding alkali and a palladium catalyst underthe protection of inert gas, and fully reacting at 90-100 DEG C to prepare an intermediate C; and 2, adding the intermediate C and a raw material D into DMSO, adding alkali and a catalyst DMAP underthe protection of inert gas, and fully reacting at 90-100 DEG C to obtain the product. The invention further discloses an organic light-emitting device containing the organic light-emitting compound,the organic light-emitting device comprises a first electrode, a second electrode and one or more organic matter layers arranged between the first electrode and the second electrode, and the organic matter layers contain the organic light-emitting compound. After the organic electroluminescent compound is applied to an organic electroluminescent device, the efficiency of the device can be improved, and the service life of the device can be prolonged.
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Paragraph 0069-0072
(2020/05/05)
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- NOVEL COMPOUND AND ORGANIC LIGHT EMITTING DEVICE COMPRISING SAME
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The present invention relates to a novel compound, capable of improving efficiency, and low driving voltage and/or lifespan characteristics in an organic light emitting device, and to an organic light emitting device including the same. The novel compound
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Paragraph 0288-0292
(2019/05/25)
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- Stereodivergent Photoelectrocyclization Reactions of Bis-aryl Cycloalkenones: Intercepting Photoelectrocyclization Intermediates with Acid
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Described here are tandem photoelectrocyclization and [1,5]-hydride shift reactions of heteroaryl-containing bis-aryl cyclohexenone derivatives that give heteroaryl-substituted dihydrophenanthrenes. This Letter demonstrates that electrocyclization intermediates can be trapped with acid when the [1,5]-hydride shift is relatively slow. From a practical perspective, the observation that the acid-mediated reaction gives a divergent stereochemical outcome when compared with the reaction run under neutral conditions makes these transformations powerful.
- Zhao, Xuchen,Song, Changqing,Rainier, Jon D.
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supporting information
p. 8611 - 8614
(2019/11/03)
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- A novel method for heterocyclic amide-thioamide transformations
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In this paper, we introduce a novel and convenient method for the transformation of heterocyclic amides into heteocyclic thioamides. A two-step approach was applied for this transformation: Firstly, we applied a chlorination of the heterocyclic amides to afford the corresponding chloroheterocycles. Secondly, the chloroherocycles and N-cyclohexyl dithiocarbamate cyclohexylammonium salt were heated in chloroform for 12 h at 61°C to afford heteocyclic thioamides in excellent yields.
- Fathalla, Walid,Ali, Ibrahim A. I.,Pazdera, Pavel
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supporting information
p. 174 - 181
(2017/02/15)
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- 1,2,4-triazole derivative having quinoxaline structure, preparation method and application thereof
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The invention discloses a 1,2,4-triazole derivative having quinoxaline structure, a preparation method and an application thereof. O-nitroaniline and hydrazine hydrate react to form a compound (II). The compound (II) reacts with MBF to prepare a compound
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- Synthesis of Novel Drug-Like Small Molecules Based on Quinoxaline Containing Amino Substitution at C-2
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A series of novel "drug-like" small molecules based on quinoxaline containing amino substitution at C-2 were synthesized. All these molecules were prepared either via the reaction of 2-phenyl-3-(piperazin-1-yl)quinoxaline with acyl bromides or benzyl bromides or various carboxylic acids or via the reaction of 2-chloro-3-phenylquinoxaline with various amines. The structures of these novel compounds were confirmed by spectral analysis. The strategy used is simple and efficient and afforded good yields of quinoxaline derivatives.
- Rao, K. Raghavendra,Raghunadh, Akula,Mekala, Ramamohan,Meruva, Suresh Babu,Ganesh, K. Ravi,Krishna,Kalita, Dipak,Laxminarayana, Eppakayala,Pal, Manojit
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p. 901 - 908
(2016/05/19)
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- Synthesis of 2-(Quinoxalin-2-ylamino-benzotriazolyl) Pentanedioic Derivatives as Potential Anti-Folate Agents
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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.
- Briguglio,Piras,Corona,Pirisi,Burrai,Boatto,Gavini,Rassu
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p. 1721 - 1737
(2016/11/23)
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- Application of hydrazone compound containing benzopyrazine structure as bactericide
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The invention discloses application of a hydrazone compound containing a benzopyrazine structure as a bactericide. A preparation method for the hydrazone compound comprises the following steps: reacting o-nitroaniline with hydrazine hydrate to prepare a c
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- Hydrazone compound containing benzopyrazine structure, and preparation method and application thereof
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The invention discloses a hydrazone compound containing a benzopyrazine structure, and a preparation method and an application thereof. The preparation method comprises the steps: preparing a compound 1 from o-nitroaniline and hydrazine hydrate; making th
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- Copper-Catalyzed Cascade Cycloamination of α-Csp3-H Bond of N-Aryl Ketimines with Azides: Access to Quinoxalines
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A copper-catalyzed cycloamination of α-Csp3-H bond of N-aryl ketimines with sodium azide has been developed. This methodology provides an efficient access to quinoxalines and features mild reaction conditions and readily available ketimines with diverse functional group tolerance.
- Chen, Tengfei,Chen, Xun,Wei, Jun,Lin, Dongen,Xie, Ying,Zeng, Wei
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p. 2078 - 2081
(2016/06/01)
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- Application of 1, 2, 4-triazole derivative with benzo pyrazine structure as bactericide
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The invention discloses application of a 1, 2, 4-triazole derivative with a benzo pyrazine structure as a bactericide. The 1, 2, 4-triazole derivative with the benzo pyrazine structure is prepared as follows: a compound (II) is prepared from ortho-nitroan
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Paragraph 0018; 0028
(2017/02/17)
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- SUBSTITUTED QUINOXALINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR4
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The present invention relates to novel quinoxaline derivatives of formula (I) as positive allosteric modulators for modulating metabotropic glutamate receptor subtype 4 (mGluR4) and/or altering glutamate level or glutamatergic signalling.
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- ORGANIC ELECTROLUMINESCENT COMPOUNDS AND ORGANIC ELECTROLUMINESCENT DEVICE COMPRISING THE SAME
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The present invention relates to a novel organic electroluminescent compound and an organic electroluminescent device comprising the same. Using the organic electroluminescent compound according to the present invention, an organic electroluminescent device can have a long lifespan, a low driving voltage, high current efficiency and high power efficiency.
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Paragraph 155; 156
(2014/06/24)
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- Facile and efficient regioselective synthesis of 1-(3′-substituted quinoxalin-2′-yl)-3-aryl/heteroaryl-5-methylpyrazoles
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This report describes an efficient and practical approach for regioselective synthesis of 1-(3′-substituted quinoxalin-2′-yl)-3- aryl/heteroaryl-5-methylpyrazoles (3a-j). Reaction of 2-chloro-3-substituted quinoxalines (1) with 3(5)-methyl-5(3)-aryl-1H-pyrazoles (2) in the presence of sodium hydride furnished the title compounds in excellent yields with good levels of regioselectivity. The present protocol is superior to the existing method, which yielded a mixture of regioisomeric pyrazoles (I, II) and triazolo[4,3-a]quinoxalines (III). Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
- Aggarwal, Ranjana,Masan, Eakta,Sumran, Garima
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p. 1842 - 1848
(2013/05/21)
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- HETEROCYCLIC DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE THEREOF
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The present invention relates to novel quinoxaline, quinazoline and phthalazine derivatives as well as multimeric derivatives, methods for their preparation, pharmaceutical compositions including such compounds, and methods of using these compounds for the treatment and prevention of brain damage resulting from brain injury, especially secondary brain damage due to traumatic brain injury (TBI). The compounds of the invention are also useful in treating and preventing neurodegenerative diseases.
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Page/Page column 34
(2010/03/02)
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- Fragment based design of new H4 receptor-ligands with anti-inflammatory properties in vivo
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Using a previously reported flexible alignment model we have designed, synthesized, and evaluated a series of compounds at the human histamine H 4 receptor (H4R) from which 2-(4-methyl-piperazin-l-yl)- quinoxaline (3) was identified as a new lead structure for H4R ligands. Exploration of the structure-activity relationship (SAR) of this scaffold led to the identification of 6,7-dichloro 3-(4-methylpiperazin-l-yl) quinoxalin-2(1H)-one (VUF 10214, 57) and 2-benzyl-3-(4-methyl-piperazin-l-yl) quinoxaline (VUF 10148, 20) as potent H4R ligands with nanomolar affinities. In vivo studies in the rat reveal that compound 57 has significant anti-inflammatory properties in the carrageenan-induced paw-edema model.
- Smits, Rogier A.,Lim, Herman D.,Hanzer, Agnes,Zuiderveld, Obbe P.,Guaita, Elena,Adami, Maristella,Coruzzi, Gabriella,Leurs, Rob,De Esch, Iwan J. P.
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p. 2457 - 2467
(2008/12/22)
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- HETEROCYCLIC DERIVATIVES BINDING TO THE PERIPHERAL-TYPE BENZODIAZEPINE RECEPTOR (PBR)
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The present invention relates to novel quinoxaline, quinazoline and phthalazine derivatives as well as multimeric derivatives, methods for their preparation, pharmaceutical compositions including such compounds, and methods of using these compounds for the treatment and prevention of brain damage resulting from brain injury, especially secondary brain damage due to traumatic brain injury (TBI). The compounds of the invention are also useful in treating and preventing neurodegenerative diseases.
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Page/Page column 65-66; 72-73; Sheet 16/26
(2008/06/13)
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- Isonitriles as efficient ligands in Suzuki-Miyaura reaction
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Isonitrile palladium complexes [(RNC)2PdCl2] were prepared and tested in Suzuki reaction of 4-chloroanisol. (AdNC)2PdCl2 was found the most effective catalyst and was used in phenylation of several chloro and bromoaromatic substrates.
- Villemin, Didier,Jullien, Arnaud,Bar, Nathalie
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p. 4191 - 4193
(2008/02/05)
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- Facile synthesis of 2,3-disubstituted quinoxalines by Suzuki-Miyaura coupling
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A versatile synthetic route to symmetrical and unsymmetrical 2,3-disubstituted quinoxalines was developed by palladium-catalyzed Suzuki-Miyaura coupling of 2,3-dichloroquinoxaline with various boronic acids. Their photophysical and electrochemical properties were investigated.
- Mao, Lisheng,Sakurai, Hidehiro,Hirao, Toshikazu
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p. 2535 - 2539
(2007/10/03)
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