51347-93-4

Basic information

• Product Name: 2-chloro-3-hydrazinylquinoxaline
• Synonyms: 2-chloro-3-hydrazinylquinoxaline;(3-Chloro-quinoxalin-2-yl)-hydrazine
• CAS NO: 51347-93-4
• Molecular Formula: C₈H₇ClN₄
• Molecular Weight: 194.62098
• Mol File: 51347-93-4.mol
• Article Data: 37

Chemical Properties

• Appearance: /
• Storage Temp.: 2-8°C
• CAS DataBase Reference: 2-chloro-3-hydrazinylquinoxaline(CAS DataBase Reference)
• NIST Chemistry Reference: 2-chloro-3-hydrazinylquinoxaline(51347-93-4)
• EPA Substance Registry System: 2-chloro-3-hydrazinylquinoxaline(51347-93-4)

Safety Data

• Hazardous Substances Data: 51347-93-4(Hazardous Substances Data)

Usage

General Description

2-chloro-3-hydrazinylquinoxaline is a chemical compound that belongs to the class of hydrazine derivatives. It is an organic compound containing a quinoxaline ring with a chlorine atom and a hydrazinyl group attached to it. 2-chloro-3-hydrazinylquinoxaline has potential applications in the field of pharmaceuticals and medicinal chemistry as it exhibits biological activities. It has been studied for its potential anti-inflammatory, antimicrobial, and antioxidant properties. Additionally, it is used as a building block in the synthesis of various heterocyclic compounds and agrochemicals. However, due to its hydrazine moiety, it is important to handle this compound with care as hydrazines are known to be toxic and potentially carcinogenic.

Upstream product

• 15804-19-0 2,3-dihydroxyquinoxaline 
• 95-54-5 1,2-diamino-benzene 
• 15804-19-0 quinoxaline-2,3-dione 
• 2213-63-0 2,3-dichloroquinoxaline 

Downstream Products

• 97111-41-6 N-(3-Chloro-quinoxalin-2-yl)-N'-[1-(4-nitro-phenyl)-meth-(E)-ylidene]-hydrazine 
• 91895-40-8 4-chloro-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline 
• 113181-21-8 1-ethyl-N-phenyl[1,2,4]triazolo[4,3-a]quinoxalin-4-amine 
• 113181-19-4 N-cyclohexyl-1-ethyl[1,2,4]triazolo[4,3-a]quinoxalin-4-amine 
• 91895-39-5 4-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline 

Relevant articles and documents

Discovery of novel [1,2,4]triazolo[4,3-a]quinoxaline aminophenyl derivatives as BET inhibitors for cancer treatment

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.

Nanomolar-Potency 1,2,4-Triazoloquinoxaline Inhibitors of the Kidney Urea Transporter UT-A1

Urea transporter A (UT-A) isoforms encoded by the Slc14a2 gene are expressed in kidney tubule epithelial cells, where they facilitate urinary concentration. UT-A1 inhibition is predicted to produce a unique salt-sparing diuretic action in edema and hyponatremia. Here we report the discovery of 1,2,4-triazoloquinoxalines and the analysis of 37 synthesized analogues. The most potent compound, 8ay, containing 1,2,4-triazolo[4,3-a]quinoxaline-substituted benzenesulfonamide linked by an aryl ether, rapidly and reversibly inhibited UT-A1 urea transport by a noncompetitive mechanism with IC50 ≈ 150 nM; the IC50 was ～2 μM for the related urea transporter UT-B encoded by the Slc14a1 gene. Molecular modeling suggested a putative binding site on the UT-A1 cytoplasmic domain. In vitro metabolism showing quinoxaline ring oxidation prompted the synthesis of metabolically stable 7,8-difluoroquinoxaline analogue 8bl, which when administered to rats produced marked diuresis and reduced urinary osmolality. 8bl has substantially improved UT-A1 inhibition potency and metabolic stability compared with prior compounds.

Introducing structure-based three-dimensional pharmacophore models for accelerating the discovery of selective BRD9 binders

A well-structured in silico workflow is here reported for disclosing structure-based pharmacophore models against bromodomain-containing protein 9 (BRD9), accelerating virtual screening campaigns and facilitating the identification of novel binders. Specifically, starting from 23 known ligands co-crystallized with BRD9, three-dimensional pharmacophore models, namely placed in a reference protein structure, were developed. Specifically, we here introduce a fragment-related pharmacophore model, useful for the identification of new promising small chemical probes targeting the protein region responsible of the acetyllysine recognition, and two further pharmacophore models useful for the selection of compounds featuring drug-like properties. A pharmacophore-driven virtual screening campaign was then performed to facilitate the selection of new selective BRD9 ligands, starting from a large library of commercially available molecules. The identification of a promising BRD9 binder (7) prompted us to re-iterate this computational workflow on a second focused in-house built library of synthesizable compounds and, eventually, three further novel BRD9 binders were disclosed (8–10). Moreover, all these compounds were tested among a panel comprising other nine bromodomains, showing a high selectivity for BRD9. Preclinical bioscreens for potential anticancer activity highlighted compound 7 as that showing the most promising biological effects, proving the reliability of this in silico pipeline and confirming the applicability of the here introduced structure-based three-dimensional (3D) pharmacophore models as straightforward tools for the selection of new BRD9 ligands.

Triazolo[4,3-a] quinoxaline and [1,2,4]triazolo[4,3- a] quinoxaline-1-thiol-derived DNA intercalators: Design, synthesis, molecular docking, in silico ADMET profiles and anti-proliferative evaluations

In view of their DNA intercalation activities as anticancer agents, 17 novel [1,2,4]triazolo[4,3-a]quinoxaline derivatives have been designed, synthesized and evaluated against HepG2, HCT-116 and MCF-7 cells. Molecular docking studies were performed to investigate the binding modes of the proposed compounds with the DNA active site. The data obtained from biological testing highly correlated with those obtained from the molecular modeling studies. MCF-7 was found to be the most sensitive cell line to the influence of the new derivatives. In particular, compound 12d was found to be the most potent derivative of all the tested compounds against the three HepG2, HCT116 and MCF-7 cancer cell lines, with IC50 = 22.08 ± 2.1, 27.13 ± 2.2 and 17.12 ± 1.5 μM, respectively. Although this compound displayed nearly one third of the activity of doxorubicin (IC50 = 7.94 ± 0.6, 8.07 ± 0.8 and 6.75 ± 0.4 μM, respectively), it may be useful as a template for future design, optimization, and investigation to produce more potent anticancer analogs. Compounds 12a, 10c and 10d displayed very good anticancer activities against the three HepG2, HCT116 and MCF-7 cancer cell lines, with IC50 = 31.40 ± 2.8, 28.81 ± 2.4 and 19.72 ± 1.5 μM for 12a, 33.41 ± 2.9, 29.96 ± 2.5 and 24.78 ± 1.9 μM for 10c, and 37.55 ± 3.3, 30.22 ± 2.6 and 25.53 ± 2.0 μM for 10d. The most active derivatives, 10c, 10d, 10h, 12a, 12b and 12d, were evaluated for their DNA binding activities. Compound 12d displayed the highest binding affinity. This compound potently intercalates DNA at a decreased IC50 value (35.33 ± 1.8 μM), which is nearly equipotent to that of doxorubicin (31.27 ± 1.8 μM). Compounds 12a and 10c exhibited good DNA-binding affinities, with IC50 values of 39.35 ± 3.9 and 42.35 ± 3.9 μM, respectively. Finally, compounds 10d, 10h and 12b showed moderate DNA-binding affinities, with IC50 values of 50.35 ± 3.9, 57.08 ± 3.3 and 59.35 ± 3.2 μM, respectively.