Heterocyclic Building Blocks-quinoxaline

Development and validation of high performance liquid chromatographic method for estimation of brimonidine tartrate as bulk drug and in ophthalmic formulation was written by Rohan, Barse;Amol, Tagalpallewar;Chandrakant, Kokare;Shrivastava, Birendra. And the article was included in International Journal of PharmTech Research in 2019.COA of Formula: C15H16BrN5O6 This article mentions the following:

Glaucoma is complex disease characterized by ocular hypertension with a progressive visual loss that could resist in blindness due to damage occurred to optic nerve. Brimonidine tartrate is commonly used drug in glaucoma therapy which is selective alpha 2 adrenergic agonist. The reverse phase high performance liquid chromatog. method was developed and validated for estimation of brimonidine tartrate in bulk drug and pharmaceutical dosage form. Better separation was achieved on Kromasil C 18 ( 250 mm X 4.6 mm i.d., 5μm particle size) column using isocratic elution program with mobile phase citric acid monohydrate buffer : water: methanol (30:50:20 volume/volume/v) and pH 3 was maintained by using triethylamine. The flow rate was 1.0 mL/min. Elute was detected at 246 nm and it effectively separated at retention time of 6 min. The developed method was successfully validated according to ICH guidelines. The method was validated for linearity, accuracy, specificity, precision and robustness. The LOD and LOQ was 1.47 and 4.47μg/mL resp. The optimized and validated method can be used for estimation of brimonidine tartrate in bulk and in ophthalmic formulation. In the experiment, the researchers used many compounds, for example, 5-Bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine (2R,3R)-2,3-dihydroxysuccinate (cas: 70359-46-5COA of Formula: C15H16BrN5O6).

5-Bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine (2R,3R)-2,3-dihydroxysuccinate (cas: 70359-46-5) belongs to quinoxaline derivatives. Condensed heterocycles of quinoxalines have become attractive targets in synthetic and medicinal chemistry due to their significant biological activities. Quinoxaline and its analogues may also be formed by reduction of amino acids substituted 1,5-difluoro-2,4-dinitrobenzene (DFDNB),One study used 2-iodoxybenzoic acid (IBX) as a catalyst in the reaction of benzil with 1,2-diaminobenzene.COA of Formula: C15H16BrN5O6

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

New quinoxaline derivatives as VEGFR-2 inhibitors with anticancer and apoptotic activity: design, molecular modeling, and synthesis was written by Alsaif, Nawaf A.;Dahab, Mohammed A.;Alanazi, Mohammed M.;Obaidullah, Ahmad J.;Al-Mehizia, Abdulrahman A.;Alanazi, Manal M.;Aldawas, Saleh;Mahdy, Hazem A.;Elkady, Hazem. And the article was included in Bioorganic Chemistry in 2021.Computed Properties of C8H4Cl2N2 This article mentions the following:

New series of [1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-one I [R = Et, Ph, 3-ClC₆H₄, etc.; X = CH₂] and [1,2,4]triazolo[4,3-a]quinoxaline derivatives I [X = SCH₂] were designed, synthesized, and biol. assessed for their anti-proliferative activities against two selected tumor cell lines MCF-7 and HepG2. Comparing to sorafenib (IC₅₀ = 2.17 ± 0.13 and 3.51 ± 0.21μM against MCF-7 and HepG2, resp.), compounds I [R = 4-ClC₆H₄, 2,5-di-ClC₆H₃, 2-HO-5-MeC₆H₃; X = CH₂, SCH₂] exhibited the highest activities against the examined cell lines with IC₅₀ values extending from 4.1 ± 0.4 to 11.7 ± 1.1μM. Furthermore, VEGFR-2 inhibitory activities were assessed for all the synthesized compounds as potential mechanisms for their anti-proliferative activities. Compounds I [R = 4-ClC₆H₄, 2,5-di-ClC₆H₃, 2-HO-5-MeC₆H₃; X = CH₂, SCH₂] displayed prominent inhibitory efficiency vs. VEGFR-2 kinase with IC₅₀ value ranging from 3.4 ± 0.3 to 6.8 ± 0.5 nM. Fascinatingly, the results of VEGFR-2 inhibitory assays were matched with that of the cytotoxicity data, where the most potent anti-proliferative derivatives exhibited promising VEGFR-2 inhibitory activities. Further studies displayed the ability of compound I [R = 4-ClC₆H₄; X = CH₂] to induce apoptosis in HepG2 cells and can arrest the growth of such cells at the G2/M phase. Also, compound I [R = 4-ClC₆H₄; X = CH₂] produced a significant increase in the level of BAX/Bcl-2 ratio (3.8-fold), caspase- 3 (1.8-fold), and caspase-9 (1.9-fold) compared to the control cells. Mol. docking studies were carried out to investigate the possible binding interaction inside the active site of the VEGFR-2. In the experiment, the researchers used many compounds, for example, 2,3-Dichloroquinoxaline (cas: 2213-63-0Computed Properties of C8H4Cl2N2).

2,3-Dichloroquinoxaline (cas: 2213-63-0) belongs to quinoxaline derivatives. Quinoxaline is isomeric with other naphthyridines including quinazoline, phthalazine and cinnoline. Quinoxaline and its analogues may also be formed by reduction of amino acids substituted 1,5-difluoro-2,4-dinitrobenzene (DFDNB),One study used 2-iodoxybenzoic acid (IBX) as a catalyst in the reaction of benzil with 1,2-diaminobenzene.Computed Properties of C8H4Cl2N2

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Quinoxalines. XXIII. Reaction of 2-chloroquinoxaline with nucleophiles was written by Iijima, Chihoko;Hayashi, Eisaku. And the article was included in Yakugaku Zasshi in 1988.Category: quinoxaline This article mentions the following:

2-Chloroquinoxaline (I, R = Cl) reacted with NaI, NaSO₂C₆H₄R¹-4 (R¹ = H, Me), or KSCN to afford quinoxaline derivatives I (R = I, SO₂C₆H₄R¹-4, SCN; R¹ = H, Me) in good yields. Cyano and nitro groups were introduced into the 2-position of quinoxaline in low yield by using KCN and AgNO. In the experiment, the researchers used many compounds, for example, Quinoxalin-2-amine (cas: 5424-05-5Category: quinoxaline).

Quinoxalin-2-amine (cas: 5424-05-5) belongs to quinoxaline derivatives. Quinoxalines have received a significant amount of attention due to their potential use in fighting various pathophysiological conditions like epilepsy, Parkinson’s, and Alzheimer’s diseases. Quinoxalines are used in the treatment of bacterial, cancer, and HIV infections. Moreover, varenicline, a clinical drug is used for treating nicotine addiction, also contains quinoxaline moiety.Category: quinoxaline

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Visible-light-promoted/PIFA-mediated direct C-H acylation of quinoxalin-2(1H)-ones with aldehydes was written by Ni, Hangcheng;Li, Yu;Deng, Jieyi;Shi, Xingzi;Pan, Qinhai. And the article was included in New Journal of Chemistry in 2021.Application of 1196-57-2 This article mentions the following:

A simple and mild synthesis of 3-acylated quinoxalinones I [R = Ph, 4-MeC₆H₄, 2-naphthyl, etc.; R¹ = H, Me, allyl, etc.] had been achieved via C-H acylation reaction of quinoxalin-2(1H)-ones with aldehydes as the radical precursors under visible-light irradiation A wide variety of functional groups could be incorporated into the products by employing diverse aldehydes and quinoxalin-2(1H)-one derivatives Also, this method was applied to the modification of natural mols. and pharmaceutically relevant compounds A mechanistic study revealed that an HAT process occurred in the acylation reaction for the generation of acyl radicals, and that PIFA ([bis(trifluoroacetoxy)iodo]benzene) acted both as the photosensitizer and oxidant in this reaction. In the experiment, the researchers used many compounds, for example, 2-Quinoxalinol (cas: 1196-57-2Application of 1196-57-2).

2-Quinoxalinol (cas: 1196-57-2) belongs to quinoxaline derivatives. Quinoxaline derivatives are important constituents of pharmacologically active compounds, including as well as for RNA synthesis inhibition, reactive dyes and pigments, azo dyes, flurox Cylin Dyes, Corrosion Inhibitors and Photovoltaic Polymers. The parent substance of the group, quinoxaline, results when glyoxal is condensed with 1,2-diaminobenzene. Substituted derivatives arise when α-ketonic acids, α-chlorketones, α-aldehyde alcohols and α-ketone alcohols are used in place of diketones.Application of 1196-57-2

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Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

CX-516 Cortex Pharmaceuticals Inc was written by Danysz, W.. And the article was included in Current Opinion in Central & Peripheral Nervous System Investigational Drugs in 1999.Safety of Piperidin-1-yl(quinoxalin-6-yl)methanone This article mentions the following:

A review with many references CX-516, an AMPA modulator from Cortex Pharmaceuticals, is in phase I/IIa clin. trials for the symptomatic treatment of deficits in memory and cognition in Alzheimer’s disease (AD) and similar disorders. CX-516 and other members in the series are also being investigated for possible antidepressant and antipsychotic activity. Results from initial studies showed that CX-691 and CX-519, both members of the AMP Akine family, have antidepressant activities. In Jan. 1999, Cortex licensed AMP Akine technol. rights to Organon for schizophrenia and depression. Cortex entered into a Cooperative Research and Development Agreement (CRADA) with the National Institute of Neurol. Diseases and Stroke, National Institutes of Health, for the initial clin. evaluation of CX-516 in AD patients in Nov. 1996. The results of a trial of CX-516 in combination with clozapine in schizophrenia patients were presented at the International Society for Schizophrenia Research in Apr. 1999. CX-516 improved a number of aspects of cognitive function. In the experiment, the researchers used many compounds, for example, Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3Safety of Piperidin-1-yl(quinoxalin-6-yl)methanone).

Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3) belongs to quinoxaline derivatives. Condensed heterocycles of quinoxalines have become attractive targets in synthetic and medicinal chemistry due to their significant biological activities. Quinoxalines are used in the treatment of bacterial, cancer, and HIV infections. Moreover, varenicline, a clinical drug is used for treating nicotine addiction, also contains quinoxaline moiety.Safety of Piperidin-1-yl(quinoxalin-6-yl)methanone

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

High-efficiency and long-lifetime deep-blue organic light-emitting diode with a maximum external quantum efficiency of 20.6% and CIE_y of 0.04 was written by Hu, Suhao;Tian, Yuhe;Lin, Yang;Shi, Wei;Pang, Yudong;Pan, Saihu;Wei, Bin. And the article was included in Dyes and Pigments in 2022.COA of Formula: C18N12 This article mentions the following:

We synthesized a diphenylamine modified pyrene derivative, 4,9-diisopropyl-N,N,N’,N’-tetrakis-(4-methyl-biphenyl-3-yl)-pyrene-1,6-diamine (DITBDAP), and successfully applied it to deep-blue organic light-emitting diodes (OLEDs). The DITBDAP-based top-emitting OLED was featured by a high maximum external quantum efficiency (EQE_max) of 20.6%, an extremely low CIE_y (Commission International de L’Eclairage coordinates) of 0.04, a narrow full-width at half maximum of 16 nm, and a long lifetime of 250 h. We chose 6,12-bis[6-trimethylphenylamino-5-trimethylphenylamino] pyrene (Bmpac) as the comparison material due to its similar structure to DITBDAP. The DITBDAP-based bottom-emitting OLED showed a better performance compared to that of the Bmpac-based OLED, with the T₉₅ lifetime (time to 95% of the initial luminance of 3000 cd m^-2) of 250 h, which was more than twice that of the Bmpac-based OLED. In addition, the efficiency roll-off was extremely low at high brightness, which were 1% at 1100 cd m^-2 and 5% at 3200 cd m^-2. The synthesized DITBDAP has realized highly efficient and long-lifetime deep-blue OLEDs with the EQE up to 20.6% and CIE_y as low as 0.04. In the experiment, the researchers used many compounds, for example, Dipyrazino[2,3-f:2′,3′-h]quinoxaline-2,3,6,7,10,11-hexacarbonitrile (cas: 105598-27-4COA of Formula: C18N12).

Dipyrazino[2,3-f:2′,3′-h]quinoxaline-2,3,6,7,10,11-hexacarbonitrile (cas: 105598-27-4) belongs to quinoxaline derivatives. Condensed heterocycles of quinoxalines have become attractive targets in synthetic and medicinal chemistry due to their significant biological activities. Quinoxaline-1,4-di-N-oxide derivatives have shown to improve the biological results and are endowed with anti-viral, anti-cancer, anti-bacterial, and anti-protozoal activities with application in many other therapeutic areas.COA of Formula: C18N12

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Ocular co-delivery of timolol and brimonidine from a self-assembling peptide hydrogel for the treatment of glaucoma: in vitro and ex vivo evaluation was written by Taka, Elissavet;Karavasili, Christina;Bouropoulos, Nikolaos;Moschakis, Thomas;Andreadis, Dimitrios D.;Zacharis, Constantinos K.;Fatouros, Dimitrios G.. And the article was included in Pharmaceuticals in 2020.Computed Properties of C15H16BrN5O6 This article mentions the following:

Effective pharmacotherapy during glaucoma treatment depends on interventions that reduce intraocular pressure (IOP) and retain the intraocular pressure lowering effect for sufficient time so as to reduce dosing frequency and enhance patient adherence. Combination anti-glaucoma therapy and dosage forms that increase precorneal residence time could therefore constitute a promising therapeutic intervention. The in-situ gel forming self-assembling peptide ac-(RADA)₄-CONH₂ was evaluated as carrier for the ocular co-delivery of timolol maleate (TM) and brimonidine tartrate (BR). The hydrogel’s microstructure and mech. properties were assessed with at. force microscopy and rheol., resp. Drug diffusion from the hydrogel was evaluated in vitro in simulated tear fluid and ex vivo across porcine corneas and its effect on the treated corneas was assessed through physicochem. characterization and histol. anal. Results indicated that timolol maleate and brimonidine tartrate co-delivery affected hydrogel’s microstructure resulting in shorter nanofibers and a less rigid hydrogel matrix. Rapid and complete release of both drugs was achieved within 8 h, while a 2.8-fold and 5.4-fold higher corneal permeability was achieved for timolol maleate and brimonidine tartrate, resp. No significant alterations were induced in the structural integrity of the corneas treated with the hydrogel formulation, suggesting that self-assembling peptide hydrogels might serve as promising systems for combination anti-glaucoma therapy. In the experiment, the researchers used many compounds, for example, 5-Bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine (2R,3R)-2,3-dihydroxysuccinate (cas: 70359-46-5Computed Properties of C15H16BrN5O6).

5-Bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine (2R,3R)-2,3-dihydroxysuccinate (cas: 70359-46-5) belongs to quinoxaline derivatives. Compounds possessing quinoxaline derivatives were bestowed with a variety of significant biological properties such as antiviral, antimalarial, anticancer, DNA intercalation, DNA duplex stabilization, and many others. Quinoxalines are used as dyes, pharmaceuticals, and antibiotics such as echinomycin, levomycin exhibiting antitumoral properties. Quinoxalines establish also the basis of anthelmintics and receptor antagonists.Computed Properties of C15H16BrN5O6

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Visible-light-driven cyanoalkylation of quinoxalinones using cyclobutanone oxime esters as the radical precursors was written by Zhao, Bin;Kong, Xianqiang;Xu, Bo. And the article was included in Tetrahedron Letters in 2019.Application In Synthesis of 6-Bromoquinoxalin-2(1H)-one This article mentions the following:

We have developed a versatile visible-light-driven cyanoalkylation of quinoxalinones under mild conditions. First, the cyanoalkyl radicals are generated from readily available cyclobutanone oxime esters under blue light irradiation Then the generated radicals react with heterocycles such as quinoxalinones to give the final cyanoalkylation products. The protocol tolerates a wide range of functional groups. Our cyanoalkylation protocol does not need cyanide-based reagents and also does not need external oxidants. In the experiment, the researchers used many compounds, for example, 6-Bromoquinoxalin-2(1H)-one (cas: 55687-34-8Application In Synthesis of 6-Bromoquinoxalin-2(1H)-one).

6-Bromoquinoxalin-2(1H)-one (cas: 55687-34-8) belongs to quinoxaline derivatives. Quinoxalines have received a significant amount of attention due to their potential use in fighting various pathophysiological conditions like epilepsy, Parkinson’s, and Alzheimer’s diseases. The antitumoral properties of quinoxaline compounds have been of interest. Recently, quinoxaline and its analogs have been investigated as the catalyst’s ligands.Application In Synthesis of 6-Bromoquinoxalin-2(1H)-one

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Molecular oxygen-mediated radical alkylation of C(sp³)-H bonds with boronic acids was written by Yang, Le;Qiu, Zhihong;Wu, Jintao;Zhao, Jianyou;Shen, Tong;Huang, Xuan;Liu, Zhong-Quan. And the article was included in Organic Letters in 2021.Name: 2-Quinoxalinol This article mentions the following:

A direct and site-specific alkylation of (sp³)C-H bond with aliphatic boronic acid was achieved. By simply heating glycinate and amines together with alkylboronic acids under an oxygen atm., a variety of unnatural α-amino acids and peptides could be obtained in good yields. In the experiment, the researchers used many compounds, for example, 2-Quinoxalinol (cas: 1196-57-2Name: 2-Quinoxalinol).

2-Quinoxalinol (cas: 1196-57-2) belongs to quinoxaline derivatives. Condensed heterocycles of quinoxalines have become attractive targets in synthetic and medicinal chemistry due to their significant biological activities. Quinoxaline-1,4-di-N-oxide derivatives have shown to improve the biological results and are endowed with anti-viral, anti-cancer, anti-bacterial, and anti-protozoal activities with application in many other therapeutic areas.Name: 2-Quinoxalinol

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Histopathologic Analysis of Conjunctival Lymphoproliferative Disease After Topical Brimonidine Use was written by Hwang, Hyung Bin;Kim, Sun Young;Ohn, Kyoung;Kim, Su-Young. And the article was included in Journal of Ocular Pharmacology and Therapeutics in 2019.Name: 5-Bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine (2R,3R)-2,3-dihydroxysuccinate This article mentions the following:

Purpose: To describe of histopathol. findings of conjunctival lymphoproliferative disease (CLD) after topical brimonidine use. Methods: This is a retrospective medical record review study, including histopathol. description. We reviewed the medical records of 208 patients (415 eyes) who were diagnosed with glaucoma and who were treated with topical brimonidine only for a min. of 6 mo. Of these, the medical records of 19 patients with suspected CLD clin. features were reviewed in detail. When CLD was suspected due to administration of brimonidine, histopathol. anal. was performed by biopsy of these lesions. In addition, immunohistochem. staining was performed to analyze lymphocyte markers in some pathol. tissues. Results: Nineteen patients had suspected CLD without definite irritative symptoms. Diffuse elevated (11 patients) or follicular lesion (8 patients) of salmon pink appearance was observed in inferior palpebral conjunctiva. Among these patients, 5 patients who agreed to conjunctival biopsy had histopathol. findings of CLD such as reactive lymphoid hyperplasia (LH) (2 cases) or atypical LH (2 cases). The mean duration of brimonidine use was 29.00 ± 20.25 mo (6-76 mo). And follow-up period after discontinuation of brimonidine was 27.93 ± 11.87 mo (12-58 mo). At the last visit, complete resolution of the lesion was seen in 13 patients, and partial improvement was observed in 6 patients. Conclusions: We found 4 cases of CLD following long-term administration of brimonidine. However, large-scale addnl. studies should be performed to establish causality, to determine whether these novel side effects were caused by long-term brimonidine treatment. In the experiment, the researchers used many compounds, for example, 5-Bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine (2R,3R)-2,3-dihydroxysuccinate (cas: 70359-46-5Name: 5-Bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine (2R,3R)-2,3-dihydroxysuccinate).

5-Bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine (2R,3R)-2,3-dihydroxysuccinate (cas: 70359-46-5) belongs to quinoxaline derivatives. Condensed heterocycles of quinoxalines have become attractive targets in synthetic and medicinal chemistry due to their significant biological activities. Quinoxaline and its analogues may also be formed by reduction of amino acids substituted 1,5-difluoro-2,4-dinitrobenzene (DFDNB),One study used 2-iodoxybenzoic acid (IBX) as a catalyst in the reaction of benzil with 1,2-diaminobenzene.Name: 5-Bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine (2R,3R)-2,3-dihydroxysuccinate

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider