491-36-1Relevant articles and documents
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.
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.
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.
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.
Discovery of New 4-Indolyl Quinazoline Derivatives as Highly Potent and Orally Bioavailable P-Glycoprotein Inhibitors
Chen, Zhe-Sheng,Dai, Qing-Qing,Li, Guo-Bo,Liu, Hong-Min,Liu, Hui,Wang, Bo,Wang, Shaomeng,Yu, Bin,Yuan, Shuo,Zhang, Jing-Ya,Zhang, Xiao-Nan,Zuo, Jia-Hui
, p. 14895 - 14911 (2021/10/12)
The major drawbacks of P-glycoprotein (P-gp) inhibitors at the clinical stage make the development of new P-gp inhibitors challenging and desirable. In this study, we reported our structure-activity relationship studies of 4-indolyl quinazoline, which led to the discovery of a highly effective and orally active P-gp inhibitor, YS-370. YS-370 effectively reversed multidrug resistance (MDR) to paclitaxel and colchicine in SW620/AD300 and HEK293T-ABCB1 cells. YS-370 bound directly to P-gp, did not alter expression or subcellular localization of P-gp in SW620/AD300 cells, but increased the intracellular accumulation of paclitaxel. Furthermore, YS-370 stimulated the P-gp ATPase activity and had moderate inhibition against CYP3A4. Significantly, oral administration of YS-370 in combination with paclitaxel achieved much stronger antitumor activity in a xenograft model bearing SW620/Ad300 cells than either drug alone. Taken together, our data demonstrate that YS-370 is a promising P-gp inhibitor capable of overcoming MDR and represents a unique scaffold for the development of new P-gp inhibitors.
Discovery of a Series of Hydroxamic Acid-Based Microtubule Destabilizing Agents with Potent Antitumor Activity
Bai, Peng,Chen, Lijuan,Kuang, Shuang,Liu, Jiang,Liu, Yan,Qiu, Qiang,Shi, Mingsong,Si, Wenting,Su, Zhengying,Tang, Minghai,Yan, Wei,Yang, Jianhong,Yang, Linyu,Yang, Zhuang,Ye, Haoyu,Zhang, Wanhua,Zhu, Zejiang
, p. 15379 - 15401 (2021/11/01)
Hydroxamic acid group is one of the characteristic pharmacophores of histone deacetylase (HDAC) inhibitors. But here, we discovered a series of hydroxamic acid-based microtubule destabilizing agents (MDAs), which were derived from shortening the length of the linker in HDAC6 inhibitor SKLB-23bb. Interestingly, the low nanomolar antiproliferative activity of these MDAs depended on the presence of hydroxamic acid groups, but their inhibitory effects on HDAC were lost. Among them, 12b showed favorable metabolism stability, high bioavailability, and potent antitumor activity in multidrug-resistant cell lines and A2780/T xenograft model. More importantly, in the patient-derived xenograft models of triple-negative breast cancer and osimertinib-resistant non-small-cell lung cancer, both 20 mg/kg oral and 10 mg/kg intravenous administration of 12b could induce more than 70% tumor inhibition without obvious toxicity. Overall, we discovered that 12b, as a novel MDA based on hydroxamic acid, could serve as a potential MDA for further investigation.