- Design, synthesis, and molecular docking studies of new [1,2,4]triazolo[4,3-a]quinoxaline derivatives as potential A2B receptor antagonists
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Abstract: Many shreds of evidence have recently correlated A2B receptor antagonism with anticancer activity. Hence, the search for an efficient A2B antagonist may help in the development of a new chemotherapeutic agent. In this article, 23 new derivatives of [1,2,4]triazolo[4,3-a]quinoxaline were designed and synthesized and its structures were confirmed by different spectral data and elemental analyses. The results of cytotoxic evaluation of these compounds showed six promising active derivatives with IC50 values ranging from 1.9 to 6.4?μM on MDA-MB 231 cell line. Additionally, molecular docking for all synthesized compounds was performed to predict their binding affinity toward the homology model of A2B receptor as a proposed mode of their cytotoxic activity. Results of molecular docking were strongly correlated with those of the cytotoxic study. Finally, structure activity relationship analyses of the new compounds were explored. Graphic abstract: [Figure not available: see fulltext.]
- Ezzat, Hany G.,Bayoumi, Ashraf H.,Sherbiny, Farag F.,El-Morsy, Ahmed M.,Ghiaty, Adel,Alswah, Mohamed,Abulkhair, Hamada S.
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p. 291 - 306
(2020/03/24)
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- Novel [1,2,4]Triazolo[4,3-a]Quinoxaline Derivative, Method For Preparing Same, And Pharmaceutical Composition For Preventing Or Treating BET Protein-Related Diseases, Containing Same As Active Ingredient
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Provided are a novel [1,2,4]triazolo[4,3-a]quinoxaline derivative, a method for preparing the same, and a pharmaceutical composition for preventing or treating bromodomain extra-terminal (BET) protein-related diseases including cancer and autoimmune disea
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Paragraph 0873-0875; 0870
(2020/02/20)
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- Novel [1,2,4]triazolo[4,3-a]quinoxaline amino phenyl derivatives or pharmaceutically acceptable salts thereof, preparation method therof and pharmaceutical composition for use in preventing or treating bromodomain extra-terminal(BET) protein activity related diseases containing the same as an active ingredient
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The present invention refers to [1, 2, 4] triazolo [4, 3 a-a] the [khwi [khwi] roh it was cut aminophenyl derivatives or pharmaceutically acceptable salts, including BET and manufacturing method of active ingredient (bromodomain extra non-terminal) a pharmaceutical composition for preventing or treating protein related disorders are disclosed. The present invention according to [1, 2, 4] triazolo [4, 3 a-a] aminophenyl derivatives of one of the [khwi [khwi] roh it was cut low concentrations in the BET protein family protein and an excellent BRD4 billion number, so that the inducing cytotoxicity against tumor cell lines, BET diseases associated with protein, in particular can be useful in preventing or treating cancer or an autoimmune disease. (by machine translation)
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- Discovery of novel [1,2,4]triazolo[4,3-a]quinoxaline aminophenyl derivatives as BET inhibitors for cancer treatment
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Bromodomain and extra-terminal (BET) proteins, a class of epigenetic reader domains has emerged as a promising new target class for small molecule drug discovery for the treatment of cancer, inflammatory, and autoimmune diseases. Starting from in silico screening campaign, herein we report the discovery of novel BET inhibitors based on [1,2,4]triazolo[4,3-a]quinoxaline scaffold and their biological evaluation. The hit compound was optimized using the medicinal chemistry approach to the lead compound with excellent inhibitory activities against BRD4 in the binding assay. The substantial antiproliferative activities in human cancer cell lines, promising drug-like properties, and the selectivity for the BET family make the lead compound (13) as a novel BRD4 inhibitor motif for anti-cancer drug discovery.
- Ali, Imran,Lee, Jooyun,Go, Areum,Choi, Gildon,Lee, Kwangho
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p. 4606 - 4613
(2017/09/29)
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- Synthesis and antimicrobial activity of some novel quinoxalines
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2-Hydrazino-3-chloroquinoxaline 2 was prepared and reacted with active methylene compounds, potassium thiocyanate, carbon disulfide, phenylisothiocyanate, acetic acid, ethyl chloroformate, triethyl orthoformate, and Lawessen's reagent (LR) to give a new class of fused quinoxalines 4-16, respectively. Also, 2,3-dihydrazinoquinoxaline 3 was prepared and reacted with carbon disulfide, phenyl isothiocyanate, and triethyl orthoformate to give the corresponding di[1,2,4] triazolo-[4,3-a:3′,4′-c]-quinoxalines 17-19, respectively. Reaction of 3 with LR gave the corresponding di[1,2,4,3] triazophospholo[4,5-a:5′,4′-c]quinoxaline-1,6-dithione (20). It was found that all synthesized compounds exhibit antimicrobial activity and that compound 20 had a broad spectrum of activity. Copyright Taylor & Francis Group, LLC.
- Soliman,Amer
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experimental part
p. 1401 - 1410
(2012/04/04)
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- 4-Aminotriazoloquinoxalines. A Novel Class of Potent Adenosine Receptor Antagonists and Potential Rapid-Onset Antidepressants
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A series of 4-aminotriazoloquinoxalines has been prepared.Many compounds from this class reduce immobility in Porsolt's behavioral despair model in rats upon acute administration and may therefore have therapeutic potential as novel and rapid acting antidepressant agents.Optimal activity in this test is associated with hydrogen, CF3, or small alkyl groups in the 1-position, with NH2, NH-acetyl, or amines substituted with small alkyl groups in the 4-position, and with hydrogen or 8-halogen substituents in the aromatic ring.Furthermore, many of these 4-aminoquinoxalines bind avidly, and in some cases very selectively, to adenosine A1 and A2 receptors.A1 affinity of these compounds was measured by their inhibition of tritiated CHA (N6-cyclohexyladenosine) binding in rat cerebral cortex membranes and A2 affinity by their inhibition of tritiated NECA (5'-(N-ethylcarbamoyl)adenosine) binding to rat striatal homogenate in the presence of cold N6-cyclopentyladenosine.Structure-activity relationship (SAR) studies show that best A1 affinity is associated with ethyl, CF3, or C2F5 in the 1-position, NH-iPr or NH-cycloalkyl in the 4-position, and with an 8-chloro substituent.Affinity at the A2 receptor is mostly dependent on the presence of an NH2 group in the 4-position and is enhanced by phenyl, CF3, or ethyl in the 1-position.The most selective A1 ligand by a factor of >3000 is 121 (CP-68,247; 8-chloro-4-(cyclohexylamino)-1-(trifluoromethyl)triazoloquinoxaline) with an IC50 of 28 nM at the A1 receptor.The most potent A2 ligand is 128 (CP-66,713; 4-amino-8-chloro-1-phenyltriazoloquinoxaline) with an IC50 of 21 nM at the A2 receptor and a 13-fold selectivity for this receptor.Representatives from this series appear to act as antagonists at both A1 and A2 receptors since they antagonize the inhibiting action of CHA on norepinephrine-stimulated cAMP formation in fat cells and they decrease cAMP accumulation induced by adenosine in limbic forebrain slices.Thus certain members of this 4-aminotriazoloquinoxaline series are among the most potent and A1 or A2 selective non-xanthine adenosine antagonists known.
- Sarges, Reinhard,Howard, Harry R.,Browne, Ronald G.,Lebel, Lorraine A.,Seymour, Patricia A.,Koe, B. Kenneth
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p. 2240 - 2254
(2007/10/02)
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- [1,2,4]Triazolo[4,3-a]quinoxalin-4-amines: A new class of A1 receptor selective adenosine antagonists
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Several [1,2,4]triazolo[4,3-a]quinoxalines that were reported as antidepressants in the patent literature were found to possess moderate affinity for the adenosine A1 and A2 receptors. On the basis of structural parallels with adenin
- Trivedi,Bruns
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p. 1011 - 1014
(2007/10/02)
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- Method of using [1,2,4]triazolo[4,3-a]quinoxaline-4-amine derivatives as antidepressant and antifatigue agents
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A series of novel [1,2,4]triazolo[4,3-a]quinoxaline-4-amine derivatives wherein the amine group is optionally substituted with lower alkyl, phenylalkyl having up to three carbon atoms in the alkyl moiety or alkanoyl having from two to five carbon atoms, or the amine group alternatively completes a piperazino ring, the quinoxaline ring is optionally substituted with fluorine, chlorine, bromine or methoxy, and the triazolo ring is optionally substituted with lower alkyl, lower perfluoroalkyl or phenyl are disclosed. These novel compounds are useful for treatment of symptoms associated with depression. Also disclosed are pharmaceutical compositions containing the novel compounds of this invention and a method of using the compounds in the treatment of depression and fatigue.
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- Method of using [1,2,4]triazolo[4,3-a]quinoxaline-4-amine derivatives as antidepressant and antifatigue agents
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A series of novel [1,2,4]triazolo[4,3-a]quinoxaline-4-amine derivatives wherein the amine group is optionally substituted with lower alkyl, phenylalkyl having up to three carbon atoms in the alkyl moiety or alkanoyl having from two to five carbon atoms, or the amine group alternatively completes a piperazino ring, the quinoxaline ring is optionally substituted with fluorine, chlorine, bromine or methoxy, and the triazolo ring is optionally substituted with lower alkyl, lower perfluoroalkyl or phenyl are disclosed. These novel compounds are useful for treatment of symptoms associated with depression. Also disclosed are pharmaceutical compositions containing the novel compounds of this invention and a method of using the compounds in the treatment of depression and fatigue.
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