Category: 89898-96-4

Deng, Jing; Feng, Enguang; Ma, Sheng; Zhang, Yan; Liu, Xiaofeng; Li, Honglin; Huang, Huang; Zhu, Jin; Zhu, Weiliang; Shen, Xu; Miao, Liyan; Liu, Hong; Jiang, Hualiang; Li, Jian published the artcile< Design and synthesis of small molecule RhoA inhibitors: a new promising therapy for cardiovascular diseases?>, Related Products of 89898-96-4, the main research area is quinoxaline derivative preparation SAR drug screen RhoA inhibitory; cardiovascular disease.

RhoA is a member of Rho GTPases, a subgroup of the Ras superfamily of small GTP-binding proteins. RhoA, as an important regulator of diverse cellular signaling pathways, plays significant roles in cytoskeletal organization, transcription, and cell-cycle progression. The RhoA/ROCK inhibitors have emerged as a new promising treatment for cardiovascular diseases. However, to date, RhoA inhibitors are macromols., and to our knowledge, small mol.-based inhibitors have not been reported. In this study, a series of first-in-class small mol. RhoA inhibitors have been discovered by using structure-based virtual screening in conjunction with chem. synthesis and bioassay. Virtual screening of ∼200,000 compounds, followed by SPR-based binding affinity assays resulted in three compounds with binding affinities to RhoA at the micromolar level. Compound I was selected for further structure modifications in considering binding activity and synthesis ease. Forty-one new compounds were designed and synthesized accordingly. It was found that eight showed high RhoA inhibition activities with IC50 values of 1.24 to 3.00 μM. A pharmacol. assay indicated that two compounds II and III demonstrated noticeable vasorelaxation effects against PE-induced contraction in thoracic aorta artery rings and served as good leads for developing more potent cardiovascular agents.

Journal of Medicinal Chemistry published new progress about Amination. 89898-96-4 belongs to class quinoxaline, and the molecular formula is C8H5N3O3, Related Products of 89898-96-4.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Teng, Qing-Hu; Yao, Yan; Wei, Wen-Xiu; Tang, Hai-Tao; Li, Jia-Rong; Pan, Ying-Ming published the artcile< Direct C-H sulfenylation of quinoxalinones with thiols under visible-light-induced photocatalyst-free conditions>, Name: 7-Nitro-2(1H)-quinoxalinone, the main research area is arylthioquinoxalinone alkylthioquinoxalinone preparation; aerobic photochem oxidative sulfenylation quinoxalinone thiol.

Quinoxalinones underwent aerobic photochem. sulfenylation/cross-dehydrogenative coupling with thiols under blue LED irradiation without added photocatalyst in NMP to give aryl- and alkylthioquinoxalinones.

Green Chemistry published new progress about Aromatic thiols Role: RCT (Reactant), RACT (Reactant or Reagent). 89898-96-4 belongs to class quinoxaline, and the molecular formula is C8H5N3O3, Name: 7-Nitro-2(1H)-quinoxalinone.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Zhu, Haizhou; Mishra, Rosalin; Yuan, Long; Abdul Salam, Safnas F.; Liu, Jing; Gray, George; Sterling, Alyssa D.; Wunderlich, Mark; Landero-Figueroa, Julio; Garrett, Joan T.; Merino, Edward J. published the artcile< Oxidative Cyclization-Induced Activation of a Phosphoinositide 3-Kinase Inhibitor for Enhanced Selectivity of Cancer Chemotherapeutics>, Safety of 7-Nitro-2(1H)-quinoxalinone, the main research area is oxidative cyclization PI3K inhibitor cancer; oxidative cyclization; phosphoinositide 3-kinase inhibitors; prodrugs; reactive oxygen species; synergy effects.

In this work, we designed a prodrug that reacts with cellular oxidative equivalent leading to ether cleavage and cyclization to release an active phosphatidylinositol 3-kinase (PI3K) inhibitor. We show that the compound reduces affinity for PI3KA relative to the PI3K inhibitor, is slow to intercellularly oxidize, and is resistant to liver microsomes. We observed modest activity in untreated acute myeloid leukemia cells and 14-fold selectivity relative to non-cancerous cells. The cellular activity of the compound can be modulated by the addition of antioxidants or oxidants, indicating the compound activity is sensitive to cellular reactive oxygen species (ROS) state. Co-treatment with cytosine arabinoside or doxorubicin was used to activate the compound inside cells. We observed strong synergistic activity specifically in acute myeloid leukemia (AML) cancer cells with an increase in selective anticancer activity of up to 90-fold. Thus, these new self-cyclizing compounds can be used to increase the selectivity of anticancer agents.

ChemMedChem published new progress about Acute myeloid leukemia. 89898-96-4 belongs to class quinoxaline, and the molecular formula is C8H5N3O3, Safety of 7-Nitro-2(1H)-quinoxalinone.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Le Douaron, Gael; Ferrie, Laurent; Sepulveda-Diaz, Julia E.; Amar, Majid; Harfouche, Abha; Seon-Meniel, Blandine; Raisman-Vozari, Rita; Michel, Patrick P.; Figadere, Bruno published the artcile< New 6-Aminoquinoxaline Derivatives with Neuroprotective Effect on Dopaminergic Neurons in Cellular and Animal Parkinson Disease Models>, Safety of 7-Nitro-2(1H)-quinoxalinone, the main research area is aminoquinoxaline preparation arylation alkynylation reaction neuroprotective effect dopamine neuron; Parkinson disease model neuroprotective effect dopamine aminoquinoxaline derivative.

Parkinson’s disease (PD) is a neurodegenerative disorder of aging characterized by motor symptoms that result from the loss of midbrain dopamine neurons and the disruption of dopamine-mediated neurotransmission. There is currently no curative treatment for this disorder. To discover druggable neuroprotective compounds for dopamine neurons, the authors have designed and synthesized a 2nd-generation of quinoxaline-derived mols. based on structure-activity relation studies, which led previously to the discovery of the authors’ 1st neuroprotective brain penetrant hit compound MPAQ (5c). Neuroprotection assessment in PD cellular models of the authors’ newly synthesized quinoxaline-derived compounds led to the selection of a better hit compound, PAQ (4c). Extensive in vitro characterization of 4c showed that its neuroprotective action is partially attributable to the activation of reticulum endoplasmic ryanodine receptor channels. Most interestingly, 4c was able to attenuate neurodegeneration in a mouse model of PD, making this compound an interesting drug candidate for the treatment of this disorder.

Journal of Medicinal Chemistry published new progress about Alkynylation. 89898-96-4 belongs to class quinoxaline, and the molecular formula is C8H5N3O3, Safety of 7-Nitro-2(1H)-quinoxalinone.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Hazeldine, Stuart T.; Polin, Lisa; Kushner, Juiwanna; Paluch, Jennifer; White, Kathryn; Edelstein, Matthew; Palomino, Eduardo; Corbett, Thomas H.; Horwitz, Jerome P. published the artcile< Design, Synthesis, and Biological Evaluation of Analogues of the Antitumor Agent, 2-{4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy}propionic Acid (XK469)>, Application In Synthesis of 89898-96-4, the main research area is chloroquinoxalinyloxyphenoxypropionic acid structure antitumor; quinoxalinyloxyphenoxypropionic acid antitumor preparation.

2-{4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy}propionic acid (XK469) I is among the most highly and broadly active antitumor agents to have been evaluated and scheduled to enter clin. trials in 2001. The mechanism or mechanisms of action of I remain to be elaborated. Accordingly, an effort was initiated to establish a pharmacophore hypothesis to delineate the requirements of the active site, via a comprehensive program of synthesis of analogs of I and evaluation of the effects of structural modification(s) on solid tumor activity. The strategy formulated chose to dissect the two-dimensional parent structure into three regions: I, ring A of quinoxaline; II, the hydroquinone connector linkage; and III, the lactic acid moiety-to determine the resultant in vitro and in vivo effects of chem. alterations in each region. Neither the A-ring unsubstituted nor the B-ring 3-chloro-regioisomer of I showed antitumor activity. The modulating antitumor effect(s) of substituents of differing electronegativities, located at the several sites comprising the A-ring of region I, were next ascertained. Thus, a halogen substituent, located at the 7-position of a 2-{4-[(2-quinoxalinyl)oxy]phenoxy}propionic acid, generated the most highly and broadly active antitumor agents. A Me, methoxy, or an azido substituent at this site generated a much less active structure, whereas 5-, 6-, 8-chloro-, 6-, 7-nitro, and 7-amino derivatives all proved to be essentially inactive. When the connector linkage (region II) of I was changed from that of a hydroquinone to either a resorcinol or a catechol derivative, all antitumor activity was lost. Of the carboxylic acid derivatives of I (region III), i.e., CONH2, CONHMe, CONMe2, CONHOH, CONHNH2, CN, or CN4H (tetrazole), only the monomethyl- and N,N-dimethylamides proved to be active.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 89898-96-4 belongs to class quinoxaline, and the molecular formula is C8H5N3O3, Application In Synthesis of 89898-96-4.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Makhloufi, A.; Baitiche, M.; Merbah, M.; Benachour, D. published the artcile< Synthesis of new quinoxaline derivatives>, HPLC of Formula: 89898-96-4, the main research area is hydroxyquinoxaline alkyl aminoalkyl halide alkylation; quinoxaline derivative preparation.

New quinoxaline derivatives were prepared by the reaction of 2-hydroxyquinoxaline (I) and alkyl or alkylaminoalkyl halides in DMF using potassium carbonate as a base. The hydroxyl group was readily converted into a thiol function by treatment with phosphorus pentasulfide and/or Lawesson’s reagent in pyridine, and the subsequent alkylation of the thiol group was carried out under phase-transfer catalyst conditions. Chlorination of I was carried out with phosphorus oxychloride. Branching of alkylamino side chains to the 2-OH, 2-SH, and 2-Cl quinoxalines resulted in the synthesis of several compounds Synthesis and alkylation of 2-hydroxy 7-nitroquinoxaline were also reported.

Synthetic Communications published new progress about Alkylation. 89898-96-4 belongs to class quinoxaline, and the molecular formula is C8H5N3O3, HPLC of Formula: 89898-96-4.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Wozniak, Marian; Baranski, Andrzej; Nowak, Krystyna; Poradowska, Henryka published the artcile< Regioselectivity of the amination of some nitroquinoxalines by liquid ammonia/potassium permanganate>, SDS of cas: 89898-96-4, the main research area is regioselective amination nitroquinoxaline; quinoxaline nitro regioselective amination.

5- And 6-nitroquinoxalines and some of their derivatives are aminated in a liquid NH3 solution of KMnO4 to yield the corresponding 2- and/or 3- and/or 5-amino compounds Quantum-chem. calculations are made to explain the regioselectivity of the amination reactions.

Liebigs Annalen der Chemie published new progress about Amination, regioselective. 89898-96-4 belongs to class quinoxaline, and the molecular formula is C8H5N3O3, SDS of cas: 89898-96-4.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Hazeldine, Stuart T.; Polin, Lisa; Kushner, Juiwanna; Paluch, Jennifer; White, Kathryn; Edelstein, Matthew; Palomino, Eduardo; Corbett, Thomas H.; Horwitz, Jerome P. published the artcile< Design, Synthesis, and Biological Evaluation of Analogues of the Antitumor Agent, 2-{4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy}propionic Acid (XK469)>, COA of Formula: C8H5N3O3, the main research area is chloroquinoxalinyloxyphenoxypropionic acid structure antitumor; quinoxalinyloxyphenoxypropionic acid antitumor preparation.

2-{4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy}propionic acid (XK469) I is among the most highly and broadly active antitumor agents to have been evaluated and scheduled to enter clin. trials in 2001. The mechanism or mechanisms of action of I remain to be elaborated. Accordingly, an effort was initiated to establish a pharmacophore hypothesis to delineate the requirements of the active site, via a comprehensive program of synthesis of analogs of I and evaluation of the effects of structural modification(s) on solid tumor activity. The strategy formulated chose to dissect the two-dimensional parent structure into three regions: I, ring A of quinoxaline; II, the hydroquinone connector linkage; and III, the lactic acid moiety-to determine the resultant in vitro and in vivo effects of chem. alterations in each region. Neither the A-ring unsubstituted nor the B-ring 3-chloro-regioisomer of I showed antitumor activity. The modulating antitumor effect(s) of substituents of differing electronegativities, located at the several sites comprising the A-ring of region I, were next ascertained. Thus, a halogen substituent, located at the 7-position of a 2-{4-[(2-quinoxalinyl)oxy]phenoxy}propionic acid, generated the most highly and broadly active antitumor agents. A Me, methoxy, or an azido substituent at this site generated a much less active structure, whereas 5-, 6-, 8-chloro-, 6-, 7-nitro, and 7-amino derivatives all proved to be essentially inactive. When the connector linkage (region II) of I was changed from that of a hydroquinone to either a resorcinol or a catechol derivative, all antitumor activity was lost. Of the carboxylic acid derivatives of I (region III), i.e., CONH2, CONHMe, CONMe2, CONHOH, CONHNH2, CN, or CN4H (tetrazole), only the monomethyl- and N,N-dimethylamides proved to be active.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 89898-96-4 belongs to class quinoxaline, and the molecular formula is C8H5N3O3, COA of Formula: C8H5N3O3.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Makhloufi, A.; Baitiche, M.; Merbah, M.; Benachour, D. published the artcile< Synthesis of new quinoxaline derivatives>, Related Products of 89898-96-4, the main research area is hydroxyquinoxaline alkyl aminoalkyl halide alkylation; quinoxaline derivative preparation.

New quinoxaline derivatives were prepared by the reaction of 2-hydroxyquinoxaline (I) and alkyl or alkylaminoalkyl halides in DMF using potassium carbonate as a base. The hydroxyl group was readily converted into a thiol function by treatment with phosphorus pentasulfide and/or Lawesson’s reagent in pyridine, and the subsequent alkylation of the thiol group was carried out under phase-transfer catalyst conditions. Chlorination of I was carried out with phosphorus oxychloride. Branching of alkylamino side chains to the 2-OH, 2-SH, and 2-Cl quinoxalines resulted in the synthesis of several compounds Synthesis and alkylation of 2-hydroxy 7-nitroquinoxaline were also reported.

Synthetic Communications published new progress about Alkylation. 89898-96-4 belongs to class quinoxaline, and the molecular formula is C8H5N3O3, Related Products of 89898-96-4.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Wozniak, Marian; Baranski, Andrzej; Nowak, Krystyna; Poradowska, Henryka published the artcile< Regioselectivity of the amination of some nitroquinoxalines by liquid ammonia/potassium permanganate>, SDS of cas: 89898-96-4, the main research area is regioselective amination nitroquinoxaline; quinoxaline nitro regioselective amination.

5- And 6-nitroquinoxalines and some of their derivatives are aminated in a liquid NH3 solution of KMnO4 to yield the corresponding 2- and/or 3- and/or 5-amino compounds Quantum-chem. calculations are made to explain the regioselectivity of the amination reactions.

Liebigs Annalen der Chemie published new progress about Amination, regioselective. 89898-96-4 belongs to class quinoxaline, and the molecular formula is C8H5N3O3, SDS of cas: 89898-96-4.

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider