24271-82-7

Basic information

• Product Name: quinazoline-5,8-dione
• Synonyms: 5,8-quinazolinedione
• CAS NO: 24271-82-7
• Molecular Formula: C₈H₄N₂O₂
• Molecular Weight: 160.1296
• Mol File: 24271-82-7.mol

Chemical Properties

• Boiling Point: 354.3°C at 760 mmHg
• Flash Point: 172°C
• Density: 1.469g/cm³
• Vapor Pressure: 3.39E-05mmHg at 25°C
• Refractive Index: 1.636
• CAS DataBase Reference: quinazoline-5,8-dione(CAS DataBase Reference)
• NIST Chemistry Reference: quinazoline-5,8-dione(24271-82-7)
• EPA Substance Registry System: quinazoline-5,8-dione(24271-82-7)

Safety Data

• Hazardous Substances Data: 24271-82-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Quinazoline-5,8-dione is used as a pharmaceutical intermediate for the development of drug candidates due to its anti-tumor and anti-inflammatory properties. It modulates various biological processes and enzyme activities, making it a promising candidate for the treatment of various diseases.
Used in Organic Synthesis:
Quinazoline-5,8-dione is used as a building block in the synthesis of various bioactive compounds, contributing to the discovery of new drugs and therapeutic agents. Its unique structure and functional groups enable the formation of diverse chemical entities with potential medicinal applications.
Used in Antiparasitic Applications:
Quinazoline-5,8-dione derivatives are used as antiparasitic agents, targeting and inhibiting the growth and proliferation of parasites. Their potential in this application area highlights their versatility and utility in combating parasitic infections.
Used in Antimicrobial Applications:
Quinazoline-5,8-dione derivatives also exhibit antimicrobial properties, making them suitable for use in the development of antibiotics and antifungal agents. Their ability to inhibit the growth of microorganisms contributes to the fight against drug-resistant infections and the discovery of novel antimicrobial therapies.

Upstream product

• 17944-05-7 5,8-dimethoxyquinazoline 
• 93-02-7 2,5-dimethoxybenzaldehyde 
• 1206-55-9 3,6-dimethoxy-2-nitrobenzaldehyde 
• 19819-19-3 N,N‘-[(3,6-dimethoxy-2-nitrophenyl)methanediyl]diformamide 
• 24271-83-8 5,8-quinazolinediole 

Downstream Products

• 85102-82-5 (9-Ethoxycarbonylamino-5,10-dioxo-5,10-dihydro-benzo[g]quinazolin-6-yl)-carbamic acid ethyl ester 

Relevant articles and documents

6-Arylamino-5,8-quinazolinediones as potent inhibitors of endothelium-dependent vasorelaxation

6-(Substituted-phenyl)amino-5,8-quinazolinediones (3) were synthesised by regioselective substitution of 5,8-quinazolinedione (5) with appropriate arylamines in the presence of Ce(III) ions. All synthesised 5,8-quinazolinediones 3 showed a potent and efficacious inhibitory effect on the acetylcholine (ACh)-induced vasorelaxation of rat aorta with the endothelium. The quinones 3, at a low concentration of 0.1 μM, reduced the maximal response with increase of EC50 values for ACh. The results indicate that quinones 3 are potent inhibitors of endothelium-dependent vasorelaxation.

A Novel Redox Modulator Induces a GPX4-Mediated Cell Death That Is Dependent on Iron and Reactive Oxygen Species

Redox modulators have been developed as an attractive approach to treat cancer. Herein, we report the synthesis, identification, and biological evaluation of a quinazolinedione reactive oxygen species (ROS) inducer, QD394, with significant cytotoxicity in pancreatic cancer cells. QD394 shows a transcriptomic profile remarkably similar to napabucasin, a cancer stemness inhibitor. Both small molecules inhibit STAT3 phosphorylation, increase cellular ROS, and decrease the GSH/GSSG ratio. Moreover, QD394 causes an iron- and ROS-dependent, GPX4 mediated cell death, suggesting ferroptosis as a major mechanism. Importantly, QD394 decreases the expression of LRPPRC and PNPT1, two proteins involved in mitochondrial RNA catabolic processes and both negatively correlated with the overall survival of pancreatic cancer patients. Pharmacokinetics-guided lead optimization resulted in the derivative QD394-Me, which showed improved plasma stability and reduced toxicity in mice compared to QD394. Overall, QD394 and QD394-Me represent novel ROS-inducing drug-like compounds warranting further development for the treatment of pancreatic cancer.

Design and Synthesis of Novel Reactive Oxygen Species Inducers for the Treatment of Pancreatic Ductal Adenocarcinoma

Altering redox homeostasis provides distinctive therapeutic opportunities for the treatment of pancreatic cancer. Quinazolinediones (QDs) are novel redox modulators that we previously showed to induce potent growth inhibition in pancreatic ductal adenocarcinoma (PDAC) cell lines. Our lead optimization campaign yielded QD325 as the most potent redox modulator candidate inducing substantial reactive oxygen species (ROS) in PDAC cells. Nascent RNA sequencing following treatments with the QD compounds revealed induction of stress responses in nucleus, endoplasmic reticulum, and mitochondria of pancreatic cancer cells. Furthermore, the QD compounds induced Nrf2-mediated oxidative stress and unfolded protein responses as demonstrated by dose-dependent increases in RNA synthesis of representative genes such as NQO1, HMOX1, DDIT3, and HSPA5. At higher concentrations, the QDs blocked mitochondrial function by inhibiting mtDNA transcription and downregulating the mtDNA-encoded OXPHOS enzymes. Importantly, treatments with QD325 were well tolerated in vivo and significantly delayed tumor growth in mice. Our study supports the development of QD325 as a new therapeutic in the treatment of PDAC.

Triazolo Quinazoline Dione Derivatives

The present invention relates to a triazolo quinazolinedione derivative. A novel synthesized triazolo quinazolinedione derivative inhibits proliferation of cancer cells, and an anticancer activity is shown in a living organism. Accordingly, a compound of the present invention can be useful in the cancer treatment field. The compound has a chemical structure of chemical formula 1.COPYRIGHT KIPO 2017

SMALL MOLECULE INDUCERS OF REACTIVE OXYGEN SPECIES AND INHIBITORS OF MITOCHONDRIAL ACTIVITY

This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinazolinedione structure which function as reactive oxygen species (ROS) inducers and inhibitors of mitochondrial activity within cancer cells (e.g., pancreatic cancer cells), and their use as therapeutics for the treatment of cancer (e.g., pancreatic cancer) and other diseases.

Ezrin inhibitors and methods of making and using

The invention encompasses compound and pharmaceutical composition comprising the compound of the following Formula (I): or pharmaceutically acceptable salts or prodrugs thereof, that are useful for inhibiting ezrin protein in a cell or for inhibiting the growth of a cancer cell.

Targeted Nanoparticles for the Delivery of Novel Bioactive Molecules to Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor prognosis and limited therapeutic options. Therefore, there is an urgent need to identify new, safe, and targeted therapeutics for effective treatment of late as well as early stage disease. Plectin-1 (Plec-1) was recently identified as specific biomarker for detecting PDAC at an early stage. We envisioned that multivalent attachment of nanocarriers incorporating certain drugs to Plec-1-derived peptide would increase specific binding affinity and impart high specificity for PDAC cells. Previously, we discovered a novel class of compounds (e.g., quinazolinediones, QDs) that exert their cytotoxic effects by modulating ROS-mediated cell signaling. Herein, we prepared novel QD242-encapsulated polymeric nanoparticles (NPs) functionalized with a peptide to selectively bind to Plec-1. Similarly, we prepared QD-based NPs densely decorated with an isatoic anhydride derivative. Furthermore, we evaluated their impact on ligand binding and antiproliferative activity against PDAC cells. The targeted NPs were more potent than the nontargeted constructs in PDAC cells warranting further development.

Synthesis and cytotoxic activity of 6-(substituted-phenyl)amino-5,8- quinazolinediones

6-Arylamino-5,8-quinazolinediones were synthesized and evaluated for in vitro cytotoxic activity against human solid tumor cell lines A549, SK-OV-3, SK-MEL-2, XF498 and HCT-15. Most of the 6-arylamino-5,8-quinazolinediones exhibited potent activity against the cell lines HCT-15 and SK-MEL-2. Birkhaeuser Boston 2004.

Cycloaddition Routes to Azaanthraquinone Derivatives. 1. Use of Azadienophiles

The mono- and diazanaphthoquinones underwent facile cycloaddition with cyclic and alicyclic dienes, and in the majority of these cycloadditions the initial 1:1-cycloadducts or their tautomers and intermediate products formed in the oxidation procedure leading to the final azaanthraquinones were isolated.Quinoline-5,8-dione and 1-methoxy-1,3-cyclohexadiene gave the 8-methoxy isomer in an essentially regiospecific cycloaddition; isoquinoline-5,8-dione, however, gave both the 5- and 8-methoxy isomers in a 2.8:1 ratio.These structural assignments were verified by alternative syntheses of the possible isomers using heteroatom-directed lithiation procedures.