29113-33-5

Usage

Uses

Used in Pharmaceutical Industry:
ETHYL 4-QUINAZOLONE-2-CARBOXYLATE is used as a key intermediate for the synthesis of 4-quinazolone-2-carboxylic acid, which is a crucial component in the development of various pharmaceutical compounds. The application reason is its ability to facilitate the creation of new drugs with potential therapeutic properties.
Used in Chemical Synthesis:
ETHYL 4-QUINAZOLONE-2-CARBOXYLATE is used as a synthetic building block for the development of novel chemical compounds in the chemical synthesis industry. The application reason is its versatile chemical structure, which allows for the creation of a wide range of products with diverse applications.

Synthesis Reference(s)

The Journal of Organic Chemistry, 27, p. 4672, 1962 DOI: 10.1021/jo01059a524

InChI:InChI=1/C11H10N2O3/c1-2-16-11(15)9-12-8-6-4-3-5-7(8)10(14)13-9/h3-6H,2H2,1H3,(H,12,13,14)

Upstream product

• 28144-70-9 anthranilic acid amide 
• 95-92-1 oxalic acid diethyl ester 

Downstream Products

• 107399-88-2 4-Oxo-3,4-dihydro-quinazoline-2-carboxylic acid (4-hydroxy-3-piperidin-1-ylmethyl-phenyl)-amide 
• 950202-53-6 C₁₈H₁₁N₃O₅ 
• 830324-98-6 3-methyl-4-oxo-3,4-dihydro-quinazoline-2-carboxylic acid (4-trifluoromethyl-phenyl)-amide 
• 153776-85-3 C₂₃H₁₈N₆O₄ 
• 113124-36-0 C₁₆H₁₄N₄O₄S 
• 491-36-1 4-Hydroxyquinazoline 
• 783371-98-2 1-phenyl-imidazo[5,1-b]quinazoline-3,9(1H,2H)dione 
• 783371-97-1 C₁₆H₁₁N₃O₃ 
• 783371-96-0 C₁₆H₁₁N₃O₃ 
• 783371-95-9 C₁₆H₁₁N₃O₃ 
• 1415355-60-0 C₁₇H₁₃N₃O₄ 
• 1415355-62-2 C₁₇H₁₃N₃O₃ 
• 1415355-64-4 C₁₈H₁₅N₃O₄ 
• 1415355-66-6 C₁₉H₁₇N₃O₅ 

Relevant academic research and scientific papers

3-Propynyl-2-substituted carboxylic acid derivatives of quinazolinone

Alkylation of quinazolinone-2-carboxylic acids with propargyl bromide in dimethylformamide in the presence of potassium carbonate afforded 3-prop-2-ynyl quinazolinone-2-substituted carboxylic acid derivatives. Further reaction of 4b-c produced 5b-c, which indicates that N-alkylation occurs before esterification with a propynyl moiety.

Scaffold hopping and redesign approaches for quinazoline based urea derivatives as potent VEGFR-2 inhibitors

In our attempt to discover effective anticancer agents, three series of novel quinazoline-based compounds have been designed, synthesized and tested as VEGFR-2 inhibitors. Five quinazoline ?2-carboxamide derivatives (5d, 5e, 5 h, 5i, 5j) revealed potent nanomolar VEGFR-2 inhibition with IC50 values of 12.1, 40.3, 15.5, 13.1 and 57.4 nM, respectively, superior to that of the reference drug sorafenib (IC50 78.9 nM). Additionally, the quinazoline 2-carboxylate derivative bearing a fluorine substituent in middle ring (7a) showed IC50 values of 14.8 nM. Most of the new synthesized compounds are examined on NCI sixty cell lines of human cancer cells. Furthermore, molecular modeling study was administered to realize any clarification of the binding mode in the inactive VEGFR-2 conformation that demonstrates compatible binding modes similar to those of sorafenib and regorafenib. Finally, several ADME descriptors were calculated through a predictive kinetic study.

Luotonin A and Its Derivatives as Novel Antiviral and Antiphytopathogenic Fungus Agents

Plant diseases caused by viruses and fungi have posed a serious threat to global agricultural production. The discovery of new leads based on natural products is an important way to innovate pesticides. In this work, natural product luotonin A was found to have good antiviral activity against tobacco mosaic virus (TMV) for the first time. A series of luotonin A derivatives were designed, synthesized, and evaluated for their antiviral activities and fungicidal activities systematically. Most compounds displayed better antiviral activities against TMV than commercial ribavirin. Compounds 9k, 12b, and 12d displayed about similar inhibitory effects as ningnanmycin (inhibitory rates of 55, 57, and 59% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively), the best antiviral agent at present, and emerged as novel antiviral leads for further research. We selected 9k for further antiviral mechanism research via transmission electron microscopy and molecular docking, which revealed that compound 9k can interact with TMV coat protein through the hydrogen bond, leading to its polymerization, thus preventing virus assembly. Further fungicidal activity tests showed that these compounds also showed broad-spectrum fungicidal activities against 14 kinds of phytopathogenic fungi. Especially, compound 14 with a 100% antifungal effect against Botrytis cinereal emerged as a lead for further research. This work provides a reference for the development of agricultural active ingredients based on Chinese medicine plants.

Discovery of luotonin A analogues as potent fungicides and insecticides: Design, synthesis and biological evaluation inspired by natural alkaloid

The prevention and control of plant diseases and insect pests is the most crucial issue facing crop protection. To discover novel pesticide candidates with diverse chemical structures from natural products, a series of luotonin A analogues were designed, synthesized and evaluated for their antifungal and insecticidal activities. Most of these compounds exhibited potent activity against Botrytis cinerea, Magnaporthe oryzae and Aphis craccivora. Among them, the antifungal activity of compound 10s against B. cinerea was comparable to azoxystrobin (EC50 = 0.09 mM) and against M. oryzae (EC50 = 0.19 mM) was slightly weaker than that of azoxystrobin (EC50 = 0.17 mM). Compounds 10k and 10o are the most active compounds against A. craccivora having identical mortality value of 42.05% at 50 μg/mL, respectively, which were slightly lower than pymetrozine (51.14%) at the same concentration. Revealed morphological changes of the fungal cell surface by scanning electron microscopy indicated that luotonin A analogues might exert their antifungal activity by destroying fungal cell membrane and cell wall. Furthermore, the results of the in vivo protective and curative activities of the compound 10s against S. sclerotiorum and B. cinerea showed that the curative effect was stronger than its protective effect and the curative effects reached 67.17% and 73.82% at 80 μg/mL respectively. The above results further demonstrated the potential of luotonin A analogues as novel fungicides and insecticides.

Synthesis, Crystal Structure, and Agricultural Antimicrobial Evaluation of Novel Quinazoline Thioether Derivatives Incorporating the 1,2,4-Triazolo[4,3- a]pyridine Moiety

A total of 22 quinazoline thioether derivatives incorporating a 1,2,4-triazolo[4,3-a]pyridine moiety were designed, synthesized, and evaluated as antimicrobial agents in agriculture. Among these compounds, the chemical structure of compound 6l was further confirmed via single-crystal X-ray diffraction analysis. The bioassay results revealed that some of the compounds possessed noticeable in vitro antibacterial activities against the tested phytopathogenic bacteria. For example, compounds 6b and 6g had EC50 values as low as 10.0 and 24.7 μg/mL against Xanthomonas axonopodis pv. citri (Xac), respectively, which were significantly better than that of the commercial agrobactericide bismerthiazol (56.9 μg/mL). Particularly, compound 6b was also found to be capable of suppressing the pathogenic bacterium Xanthomonas oryzae pv. oryzae (Xoo) approximately 12-fold more potent than control bismerthiazol, in terms of their EC50 values (7.2 versus 89.8 μg/mL). Importantly, the most active compound 6b turned out to be one with the highest hydrophilicity and the lowest molecular weight within the series. In vivo bioassays further showed the application prospect of 6b as a promising plant bactericide for controlling Xoo. Additionally, in vitro antifungal activities of these compounds were also evaluated at the concentration of 50 μg/mL. Overall, the present study demonstrated the potential of 1,2,4-triazolo[4,3-a]pyridine-bearing quinazoline thioether derivatives as efficient agricultural antibacterial agents for crop protection.

Synthesis and Antimicrobial Activities of Novel Quinazolinone Acylhydrazone Derivatives Containing the Indole Moiety

A series of novel quinazolinone acylhydrazone derivatives containing the indole moiety were designed, synthesized, and evaluated for their inhibition activities against some important phytopathogens in vitro. Antibacterial experiments indicated that some compounds exhibited remarkable inhibition activities against tested bacteria. Especially, the EC50 values of 7a (EC50?=?55.13?μg/mL against Xoo, EC50?=?56.92?μg/mL against Rs) demonstrated the best antibacterial activities against Xoo and Rs than the other compounds, and the control agents Bismerthiazol (EC50?=?89.80?μg/mL against Xoo) and Thiodiazole copper (EC50?=?189.52?μg/mL against Rs), moreover, compound 7o (EC50?=?50.80?μg/mL) displayed the excellent activity against Xac than the control Bismerthiazol (EC50?=?56.92?μg/mL).

Application of luotonin A derivatives in preparation of drugs for preventing or resisting plant diseases

The invention relates to natural pharmaceutical chemistry field and technical field of biopesticides and discloses application of any compound of luotonin A derivatives (Ia)-(Ii) in the preparation ofdrugs for preventing or resisting grape gray mold rot and rice blast. The compounds provided by the invention are derived from natural structure derivatives of a Chinese herbal medicine, namely peganum nigellastrum, have the characteristics of no pollution, safety and high efficiency, have the advantages of natural source pesticides, can be developed into plant source pesticides for producing environment-friendly and pollution-free agricultural products and belong to novel biopesticides.

1,2,3-Triazole-quinazolin-4(3H)-one conjugates: evolution of ergosterol inhibitor as anticandidal agent

The present study describes the synthesis of 1,2,3-triazole-quinazolinone conjugates (5a-q) from ethyl 4-oxo-3-(prop-2-ynyl)-3,4-dihydroquinazoline-2-carboxylate and phenyl azide/substituted phenyl azides employing Cu(i) catalysed Huisgen 1,3-dipolar cycloaddition. The corresponding acids (6a-q) were obtained by hydrolysis of esters (5a-q) to study the effect of these functionalities on the biological activity. All synthesized compounds were screened for in vitro anticandidal evaluation against Candia albicans, Candida glabrata and Candida tropicalis strains. The results indicated that compound 5n showed potent anticandidal activity with IC50 in the range of 8.4 to 14.6 μg mL?1. Hemolytic activity using human red blood cells (hRBCs) and cytotoxicity by MTT assay on human embryonic kidney (HEK-293) cells revealed the non-toxic nature of the selected compounds. Growth kinetic study with compound 5n showed its fungicidal nature as no significant growth of Candida cells was observed even after 24 h. Cellular ergosterol content was determined in the presence of different concentrations of 5n to measure the activity of lanosterol 14α-demethylase indirectly. The results showed significant disruption of the ergosterol biosynthetic pathway through inhibition of lanosterol 14α-demethylase activity supported by docking studies (PDB: 5v5z). Overall, this study demonstrates the anticandidal potential of 5n which can serve as the lead for further structural optimization and SAR studies.

A class of 2,3-lactam ring fused quinazoline-4(3H)-one derivatives, preparation methods and applications thereof

The invention discloses a class of 2,3-lactam ring fused quinazoline-4(3H)-one derivatives, a preparation method and applications thereof. According to the present invention, a series of novel-structure simplified tricyclic fused quinazoline derivatives are designed and synthesized by using the fused quinazoline ring contained in a natural product luotonin A as a template, and an anti-liver-cancer-cell activity testing experiment is performed on the derivatives, such that a certain research direction is provided for the structural transformation of the luotonin and the camptothecin, and the novel guide structure is provided for the further discovery of the antitumor drugs. According to the present invention, the results of the multiple tests verify that the method relates to the continuous 4-5 step traditional chemical reaction (intermolecular cyclization, alkylation, amination, intramolecular cyclization and substitution), it is proved that the yield of the final product is easily improved by setting the reaction sequence from a plurality of the fields, the whole synthesis route for the synthesis of the compounds is firstly and publicly reported, and the reference method can be provided for the synthesis of a large number of the derivatives and the structural transformation.

Synthesis and evaluation of antiproliferative activity of novel quinazolin-4(3H)-one derivatives

Two series of novel quinazolin-4(3H)-one derivatives (10a–g and 11a–g) have been synthesized and evaluated for their in vitro antiproliferative activity against human HeLa, MIAPACA, MDA-MB-231, and IMR-31 cancer cell lines. The synthesized compounds were characterized by spectral (Fourier transform infrared, 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, high-resolution mass spectra) methods. Among them, compounds 11e and 11g exhibited potent in vitro antiproliferative activity with GI50 values 0.02, less than 0.01 μM against MIAPACA human cancer cell line. Significantly, compounds 10a, 10b, 10c, 10g, 11b, 11c, 11d, 11e, 11f showed activity with GI50 values ranging from 0.1 to 0.87 μM against human cancer cell lines MIAPACA, MDA-MB-231, and IMR-31. We have explored the probable binding mode and key active site interactions in HDAC8 and EHMT2 proteins. The docking results are complementary to the experimental results.