491-36-1Relevant academic research and scientific papers
Application of organolithium in organic synthesis: A simple and convenient procedure for the synthesis of more complex 6-substituted 3H-quinazolin-4-ones
El-Hiti, Gamal A.
, p. 323 - 331 (2004)
6-Methyl-3H-quinazolin-4-one reacted with alkyllithium reagents at -78°C in THF to give 2-alkyl-1,2-dihydro-6-methyl-3H-quinazolin-4-ones in high yields. However, no reaction took place when LDA was used as the lithium reagent. 6-Bromo-3H-quinazolin-4-one reacted with excessive butyllithium to give 2-butyl-1,2-dihydro-3H-quinazolin-4-ones in very good yields. However, the lithiation of 6-bromo-3H-quinazolin-4-one was achieved by the use of a combination of methyllithium (1.1 equivalents) and tert-butyllithium (2.2 equivalents) at -78°C in THF. The dilithio reagent thus obtained reacted with a variety of electrophiles (H2O, iodoethane, benzaldehyde, anisaldehyde, cyclohexanone, 2-hexanone, benzophenone, phenyl isothiocyanate, TITD) to give the corresponding 6-substituted 3H-quinazolin-4-ones in excellent yields. Reaction of the dilithio reagent with 1,3-dibromopropane gave 6,6′-(propanediyl)bis(3H-quinazolin-4-one). Springer-Verlag 2003.
Total Synthesis of Luotonin A and Rutaecarpine from an Aldimine via the Designed Cyclization
Kwon, Se Hyun,Seo, Hong-Ahn,Cheon, Cheol-Hong
, p. 5280 - 5283 (2016)
The total synthesis of rutaecarpine (1) and luotonin A (2) is described through controlled cyclization of a common aldimine intermediate 5 derived from ethyl-2-aminocinnamate and quinazolinone-2-carbaldehyde. The cyanide-mediated imino-Stetter reaction of aldimine 5 provided the corresponding indole derivative 3, from which the total synthesis of rutaecarpine (1) was completed via the formation of a 6-membered C-ring. On the other hand, microwave-assisted thermal 6π-electrocyclization of the common intermediate 5, followed by the formation of a 5-membered C′-ring, allowed the completion of the total synthesis of luotonin A (2).
Synthesis and antifungal activities of N3-substituted quinazolin-4-one catalyzed by 3-Methylimidazole ionic liquids
Liu,Liu,Ji,Sun,Liu,Wen,Xu
, p. 9853 - 9856 (2013)
N3-Substituted quinazolin-4-one was synthesized by alkyl bromide and quinazolin-4-one was synthesized by anthranilic acid and formamide, catalyzing in various 3-methylimidazole ionic liquids and TBAB. The results showed that the yield of N3-substituted quinazolin-4-one increased appreciably and the reaction time shorted under ionic liquids and TBAB. Using 1-methyl-3-(2-hydroxyl-3- acetoxylpropyl)imidazolium fluoroborate or 1-propyl-3-methylimidazole fluoroborate as catalyst, the yield of N3-benzylquinazolin-4-one reached 85.1 and 82.0 %, increased 27 % more than the yield of traditional conditions. The compounds were evaluated for their in vitro antifungal activity against Fusarium graminearum, Fusarium oxysporum and Cytospora mandshurica. Compound 3f inhibited Fusarium graminearum with EC 50 28.85 μg/mL, Fusarium oxysporum with EC50 24.68 μg/mL and Cytospora mandshurica with EC50 37.67 μg/mL.
Di-4(3H)-quinazolinon-2-yl derivatives from the diacid chlorides of pinic and sym-homopinic acids
Avotin'sh,Petrova,Strakov
, p. 1241 - 1243 (2001)
The corresponding diamides have been synthesized by the interaction of the diacid chlorides of cis-2,2-dimethyl-3-carboxycyclobutaneacetic acid (pinic acid) and cis-2,2-dimethylcyclobutane-1,3-diacetic acid (sym-homopinic acid) with two equivalents of anthranilic acid. Treatment of the diamides with formamide gave 2,2-dimethyl-1-[4(3H)-quinazolinon-2-yl]methyl-3- [4(3H)-quinazolinon-2-yl]cyclobutane and 2,2-dimethyl-1,3-di[4(3H)-quinazolinon-2-ylmethyl]cyclobutane respectively.
2-(3-ethyl-2,2-dimethylcyclobutyl-methyl)-4(3H)-quinazolinones
Avotin'sh,Petrova,Pastors,Strakov
, p. 722 - 728 (1999)
Anthranilic acid and its 5-bromo and 4-chloro derivatives react with pinanoic and pinonoic acid chlorides to give the corresponding N-acyl derivatives. The pinanoyl derivatives give the corresponding 2-(3-ethyl-2,2-dimethyl-cyclobutylmethyl)-4-(3H)-quinazolinones when refluxed in formamide. Pinanoylanthranilic acid reacts with dicyclohexylcarbodiimide to give 2-(3-ethyl-2,2-dimethyl-cydobutylmethyl)benz-3,1-oxazin-4(H)-one and subsequently with hydrazine hydrate to give 3-amino-2-(3-ethyl-2,2-dimethylcyclobutylmethyl)-4(3H)-quinazolinone. Refluxing of the pinanoyl- and pinonoylanthranilic acids with acetic anhydride gives acetylanthranilic acid, and pinonoylanthranilic acid gives 4(3H)-quinazolinone with formamide. 1999 KluwerAcademic/Plenum Publishers.
Synthesis and biological activities of novel quinazolinone derivatives containing a 1,2,4-triazolylthioether moiety
Yan, Bo-Ren,Lv, Xin-Yang,Du, Huan,Gao, Man-Ni,Huang, Jian,Bao, Xiao-Ping
, p. 983 - 993 (2016)
A series of novel quinazolinone derivatives containing a 1,2,4-triazolylthioether moiety were synthesised and their antimicrobial activities were evaluated. All the target compounds were characterised by 1H NMR, 13C NMR, ESI-MS, IR and elemental analyses. The single crystal structure of 3-((5-((2-fluorobenzyl)thio)-4-phenyl-4H-1,2,4-triazol-3-yl)methyl)quinazolin-4(3H)-one (VIIi) was also determined. The preliminary bioassays indicated that some of the target compounds possessed good antimicrobial activities. For example, 3-((4-phenyl-5-((4-(trifluoromethyl)benzyl)thio)-4H- 1,2,4-triazol-3-yl)methyl)quinazolin-4(3H)-one (VIIs) exhibited the best inhibitory effect against Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri with the half-effective concentration (EC50) values of 47.6 μg mL-1 and 22.1 μg mL-1, respectively, which were superior to the commercial bactericide, bismerthiazol. Meanwhile, 3-((5-((4-chlorobenzyl)thio)-4-phenyl-4H- 1,2,4-triazol-3-yl)methyl)quinazolin-4(3H)-one (VIIh) exhibited better fungicidal activities against Pellicularia sasakii and Colletotrichum capsici at the concentration of 50 μg mL-1, in comparison with the commercial fungicide, hymexazol.
A new approach to the facile synthesis of 2-substituted-quinazolin-4(3H)- ones
Wang, Bin,Li, Zeng,Wang, Xiao Ning,Tan, Jia Heng,Gu, Lian Quan,Huang, Zhi Shu
, p. 951 - 953 (2011)
A new approach to the facile synthesis of 2-substituted-quinazolin-4(3H)- ones and its derivatives using the condensation reaction of substituted 2-aminobenzamide and orthoesters is reported.
Design, synthesis, and evaluation of novel (E)-N'-(3-allyl-2-hydroxy)benzylidene-2-(4-oxoquinazolin-3(4H)-yl)acetohydrazides as antitumor agents
Dung, Do T. M.,Park, Eun J.,Anh, Duong T.,Hai, Pham-The,Huy, Le D.,Jun, Hye W.,Kwon, Joo-Hee,Young Ji,Kang, Jong S.,Tung, Truong T.,Dung, Phan T. P.,Han, Sang-Bae,Nam, Nguyen-Hai
, (2021/10/25)
In our continuing search for novel small-molecule anticancer agents, we designed and synthesized a series of novel (E)-N'-(3-allyl-2-hydroxy)benzylidene-2-(4-oxoquinazolin-3(4H)-yl)acetohydrazides (5), focusing on the modification of substitution in the quinazolin-4(3H)-one moiety. The biological evaluation showed that all 13 designed and synthesized compounds displayed significant cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). The most potent compound 5l displayed cytotoxicity up to 213-fold more potent than 5-fluorouracil and 87-fold more potent than PAC-1, the first procaspase-activating compound. Structure–activity relationship analysis revealed that substitution of either electron-withdrawing or electron-releasing groups at positions 6 or 7 on the quinazolin-4(3H)-4-one moiety increased the cytotoxicity of the compounds, but substitution at position 6 seemed to be more favorable. In the caspase activation assay, compound 5l was found to activate the caspase activity by 291% in comparison to PAC-1, which was used as a control. Further docking simulation also revealed that this compound may be a potent allosteric inhibitor of procaspase-3 through chelation of the inhibitory zinc ion. Physicochemical and ADMET calculations for 5l provided useful information of its suitable absorption profile and some toxicological effects that need further optimization to be developed as a promising anticancer agent.
Facile N-Formylation of Amines on Magnetic Fe3O4?CuO Nanocomposites
Datta Khanal, Hari,Mishra, Kanchan,Rok Lee, Yong
, p. 4477 - 4484 (2021/08/30)
A facile, eco-friendly, efficient, and recyclable heterogeneous catalyst is synthesized by immobilizing copper impregnated on mesoporous magnetic nanoparticles. The surface chemistry analysis of Fe3O4?CuO nanocomposites (NCs) by XRD and XPS demonstrates the synergistic effect between Fe3O4 and CuO nanoparticles, providing mass-transfer channels for the catalytic reaction. TEM images clearly indicate the impregnation of CuO onto mesoporous Fe3O4. This hydrothermally synthesized eco-friendly and highly efficient Fe3O4?CuO NCs are applied as a magnetically retrievable heterogeneous catalyst for the N-formylation of wide range of aliphatic, aromatic, polyaromatic and heteroaromatic amines using formic acid as a formylating agent at room temperature. The catalytic activity of the NCs for N-formylation is attributable to the synergistic effect between Fe3O4 and CuO nanoparticles. The N-formylated product is further employed for the synthesis of biologically active quinolone moieties.
6-Nitro-Quinazolin?4(3H)?one Exhibits Photodynamic Effects and Photodegrades Human Melanoma Cell Lines. A Study on the Photoreactivity of Simple Quinazolin?4(3H)?ones
Panagopoulos, Anastasios,Balalas, Thomas,Mitrakas, Achilleas,Vrazas, Vassilios,Katsani, Katerina R.,Koumbis, Alexandros E.,Koukourakis, Michael I.,Litinas, Konstantinos E.,Fylaktakidou, Konstantina C.
, p. 826 - 836 (2021/02/03)
Photochemo and photodynamic therapies are minimally invasive approaches for the treatment of cancers and powerful weapons for competing bacterial resistance to antibiotics. Synthetic and naturally occurring quinazolinones are considered privileged anticancer and antibacterial agents, with several of them to have emerged as commercially available drugs. In the present study, applying a single-step green microwave irradiation mediated protocol we have synthesized eleven quinazolinon?4(3H)?ones, from cheap readily available anthranilic acids, in very good yields and purity. These products were irradiated in the presence of pBR322 plasmid DNA under UVB, UVA and visible light. Four of the compounds proved to be very effective DNA photocleavers, at low concentrations, being time and concentration dependent as well as pH independent. Participation of reactive oxygen species was related to the substitution of quinazolinone derivatives. 6-Nitro-quinazolinone in combination with UVA irradiation was found to be in vitro photodestructive for three cell lines; glioblastoma (U87MG and T98G) and mainly melanoma (A?375). Thus, certain appropriately substituted quinazolinones may serve as new lead photosensitizers for the development of promising biotechnological applications and as novel photochemo and photodynamic therapeutics.
