120589-86-8Relevant articles and documents
Quinoxalin-2(1H)-one derived AMPA-receptor antagonists: Design, synthesis, molecular docking and anticonvulsant activity
El-Helby, Abdel-Ghany A.,Ayyad, Rezk R. A.,El-Adl, Khaled,Elwan, Alaa
, p. 2967 - 2984 (2017)
A new series of 4-acetyl-1-substituted-3,4-dihydroquinoxalin-2(1H)-ones (3–14) were designed and synthesized in order to evaluate their α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor antagonism as a proposed mode of their anticonvulsant activity. The structure of the synthesized compounds was confirmed by elemental analysis and spectral data (infrared, 1H nuclear magnetic resonance (NMR), 13CNMR, and mass). The molecular design was performed for all synthesized compounds to predict their binding affinity towards AMPA-receptor in order to rationalize their anticonvulsant activity in a qualitative way and explain the possible interactions that might take place between the tested derivatives and AMPA receptor in comparing to compounds III and YM872 in order to obtain the anticonvulsant effect. The data obtained from the molecular modeling was strongly correlated with that obtained from the biological screening which revealed that; compounds 14b, 14a, and 13b showed the highest binding affinities toward AMPA-receptor and also showed the highest anticonvulsant activities against pentylenetetrazole-induced seizures in experimental mice. The relative potencies of these compounds were 1.89, 1.83, and 1.51 respectively, in comparing to diazepam.
Design, synthesis and biological evaluation of quinoxaline compounds as anti-HIV agents targeting reverse transcriptase enzyme
Estrin, Darío,Fabian, Lucas,Gómez, Natalia,Moglioni, Albertina,Salvatori, Melina,Taverna Porro, Marisa,Turk, Gabriela
, (2019/12/30)
Infection by human immunodeficiency virus still represents a continuous serious concern and a global threat to human health. Due to appearance of multi-resistant virus strains and the serious adverse side effects of the antiretroviral therapy administered, there is an urgent need for the development of new treatment agents, more active, less toxic and with increased tolerability to mutations. Quinoxaline derivatives are an emergent class of heterocyclic compounds with a wide spectrum of biological activities and therapeutic applications. These types of compounds have also shown high potency in the inhibition of HIV reverse transcriptase and HIV replication in cell culture. For these reasons we propose, in this work, the design, synthesis and biological evaluation of quinoxaline derivatives targeting HIV reverse transcriptase enzyme. For this, we first carried out a structure-based development of target-specific compound virtual chemical library of quinoxaline derivatives. The rational construction of the virtual chemical library was based on previously assigned pharmacophore features. This library was processed by a virtual screening protocol employing molecular docking and 3D-QSAR. Twenty-five quinoxaline compounds were selected for synthesis in the basis of their docking and 3D-QSAR scores and chemical synthetic simplicity. They were evaluated as inhibitors of the recombinant wild-type reverse transcriptase enzyme. Finally, the anti-HIV activity and cytotoxicity of the synthesized quinoxaline compounds with highest reverse transcriptase inhibitory capabilities was evaluated. This simple screening strategy led to the discovery of two selective and potent quinoxaline reverse transcriptase inhibitors with high selectivity index.
Design, molecular docking and synthesis of some novel 4-acetyl-1-substituted-3,4-dihydroquinoxalin-2(1H)-one derivatives for anticonvulsant evaluation as AMPA-receptor antagonists
El-Helby, Abdel-Ghany A.,Ayyad, Rezk R. A.,El-Adl, Khaled,Sakr, Helmy,Abd-Elrahman, Ashraf A.,Eissa, Ibrahim H.,Elwan, Alaa
, p. 3030 - 3046 (2016/11/09)
A new series of 4-acetyl-1-substituted-3,4-dihydroquinoxalin-2(1H)-ones (2–13) were designed and synthesized in order to evaluate their AMPA-receptor antagonism as a potential mode of anticonvulsant activity. The structure of the synthesized compounds was
High-affinity α-aminobutyric acid A/benzodiazepine ligands: Synthesis and structure - Activity relationship studies of a new series of tetracyclic imidazoquinoxalines
Mickelson, John W.,Jacobsen, E. Jon,Carter, Donald B.,Im, Haesook K.,Im, Wha Bin,Schreur, Peggy J. K. D.,Sethy, Vimala H.,Tang, Andy H.,McGee, James E.,Petke, James D.
, p. 4654 - 4666 (2007/10/03)
A series of tetracyclic imidazoquinoxaline analogs was developed which constrain the carbonyl group of the partial agonist 3-(5-cyclopropyl-1,2,4- oxadiazol-3-yl)-5-[(dimethylamino)carbonyl]4,5-dihydroimidazo[1,5- a]quinoxaline (2, U-91571) away from the benzene ring. These analogs orient the carbonyl group in the opposite direction of the previously reported full agonist 1-(5-cyclopropyl- 1,2,4-oxadiazol-3-yl)- 12,12a-dihydroimidazo[1,5- a]pyrrolo[2,1-c]quinoxalin- 10(11H)one (3, U-89267). A number of approaches were utilized to form the 'bottom' ring of this tetracyclic ring system including intramolecular cyclizations promoted by Lewis acids or base, as well as metal-carbenoid conditions. The size and substitution pattern of the additional ring was widely varied. Analogs within this series had high affinity for the benzodiazepine receptor on the α-aminobutyric acid A chloride ion channel complex. From TBPS shift and Cl- current assays, the in vitro efficacy of compounds within this class ranged from antagonists to partial agonists with only 18a identified as a full agonist. Additionally, several analogs were quite potent at antagonizing metrazole-induced seizures indicating possible anticonvulsant or anxiolytic activity. Unlike 3, analogs in this series did not have high affinity for the diazepam insensitive α6β2δ2 subtype. These results suggest that either constraining the carbonyl group away from the benzene ring or the greater planarity that results from the additional cyclic structure provides analogs with partial agonist properties and prevents effective interaction with the α6β2δ2 subtype.
Imidazo[1,5-A]quinoxalines
-
, (2008/06/13)
An invention relating to Imidazo[1,5-a]quinoxalines (I) STR1 which do not contain an endocyclic carbonyl group and which are useful as anxiolytic and sedative/hypnotic agents.
Antagonist, Partial Agonist, and Full Agonist Imidazoquinoxaline Amides and Carbamates Acting through the GABAA/benzodiazepine Receptor
TenBrink, Ruth E.,Im, Wha B.,Sethy, Vimala H.,Tang, Andrew H.,Carter, Don B.
, p. 758 - 768 (2007/10/02)
(4RS)-1-(5-Cyclopropyl-1,2,4-oxadiazol-3-yl)-12,12a-dihydroimidazopyrroloquinoxalin-10(11H)-one (1a), 5-benzoyl-3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-4,5-dihydroimidazoquinoxaline (13b), and tert-butyl (4S)-12,12a-dihydroimidazopyrroloquinoxaline-1-carboxylate (1e), as well as other imidazoquinoxaline amides and carbamates, represent a new series of compounds which bind with high affinity to the GABAA/benzodiazepine receptor.These compound exhibit a wide range of intrinsic efficacies as measured by TBPS binding ratios.The synthesis of 1a begins with the addition of DL-glutamic acid to 1-fluoro-2-nitrobenzene, followed by reduction of the nitro group and subsequent ring closure to form 3-(carbethoxymethyl)-1,2,3,4-tetrahydroquinoxalin-2-one, followed by a second ring closure to afford (4RS)-1,5-dioxo-1,2,3,4,5,6-hexahydropyrroloquinoxaline as the key intermediate.Appendage of a substituted imidazo ring via the anion of 5-cyclopropyl-1,2,4-oxadiazol-3-yl gives 1a.The (-) and (+)-isomers of 1a were prepared from 1-fluoro-2-nitrobenzene and L- and D-glutamic acid, respectively. 1a and its enantiomers demonstrated affinity for flunitrazepam binding site with Ki's of 0.87, 0.62, and 0.65 nM, respectively.
Reaction of 4-substituted 1,2-phenylenediamine with chloroacetic acid and α, β-unsaturated carboxylic acids: Determination of the structure of the isomers formed using long-range carbon-proton coupling
Kalyanam, Nagabhushanam,Manjunatha, Sulur G
, p. 415 - 420 (2007/10/02)
The reaction between 4-chloro-1,2-phenylenediamine with sodium salt of chloroacetic acid yields 8-chlorotetrahydroquinoxalin-2-one, o-Phenylenediamines substituted at position-4 yield a single benzodiazepinone on reaction with α,β-unsaturated aliphatic carboxylic acids.The structures of the products formed are established from 13C NMR of the products and their acyl derivatives, sometimes, using long range carbon-proton couplings.
Synthesis and aldose reductase inhibitory activity of N-1,N-4-disubstituted 3,4-dihydro-2(1H)-quinoxalinone derivatives
Sarges,Lyga
, p. 1475 - 1479 (2007/10/02)
Synthetic routes have been developed for the preparation of 4-acylated, 4-benzenesulfonylated, and 4-methylated 3,4-dihydro-2(1H)-quinoxalinone-1-acetic acids. One example of the corresponding propionic acid has also been made. These compounds have been evaluated for their ability to inhibit bovine lens aldose reductase in vitro. Some members from this series also show weak activity in vivo, inhibiting sorbitol formation in sciatic nerves of streptozotocin-diabetic rats.
