100954-32-3Relevant academic research and scientific papers
A Domino Process for the Sustainable Synthesis of Quinazolin-4(3 H)-ones with Direct Chemo- and Regioselective Bromination
Sheikhi, Ehsan,Adib, Mehdi,Yazzaf, Rozita,Jahani, Mehdi,Ghavidel, Mehdi
, p. 2046 - 2050 (2018)
An efficient approach is reported for the direct and sustainable construction of quinazolin-4(3 H)-ones through a three-component reaction of isatoic anhydride, primary amines, and bromoacetyl bromide or chloroacetyl chloride in the presence of K 2 CO 3 in DMSO. With bromoacetyl bromide, mono- or dibrominated quinazolinone scaffolds were obtainable in a chemo- and regioselective manner.
Hit-to-lead optimization and discovery of a potent, and orally bioavailable G protein coupled receptor kinase 2 (GRK2) inhibitor
Xu, Guozhang,Gaul, Michael D.,Liu, Zhijie,DesJarlais, Renee L.,Qi, Jenson,Wang, Weixue,Krosky, Daniel,Petrounia, Ioanna,Milligan, Cynthia M.,Hermans, An,Lu, Hua-Rong,Huang, Devine Zheng,Xu, June Zhi,Spurlino, John C.
, (2020)
G-protein coupled receptor kinase 2 (GRK2), which is upregulated in the failing heart, appears to play a critical role in heart failure (HF) progression in part because enhanced GRK2 activity promotes dysfunction of β-adrenergic signaling and myocyte death. An orally bioavailable GRK2 inhibitor could offer unique therapeutic outcomes that cannot be attained by current heart failure treatments that directly target GPCRs or angiotensin-converting enzyme. Herein, we describe the discovery of a potent, selective, and orally bioavailable GRK2 inhibitor, 8h, through high-throughput screening, hit-to-lead optimization, structure-based design, molecular modelling, synthesis, and biological evaluation. In the cellular target engagement assays, 8h enhances isoproterenol-mediated cyclic adenosine 3′,5′-monophosphate (cAMP) production in HEK293 cells overexpressing GRK2. Compound 8h was further evaluated in a human stem cell-derived cardiomyocyte (HSC-CM) contractility assay and potentiated isoproterenol-induced beating rate in HSC-CMs.
Design, synthesis, and biological evaluation of novel 6-(pyridin-3-yl) quinazolin-4(3H)-one derivatives as potential anticancer agents via PI3K inhibition
Yang, Huarong,Li, Qing,Su, Mingzhi,Luo, Fang,Liu, Yahua,Wang, Daoping,Fan, Yanhua
, (2021)
Abnormal activation of the PI3K/Akt pathway is demonstrated in most of human malignant tumors via regulation of proliferation, cell cycle, and apoptosis. Therefore, drug discovery and development of targeting the PI3K/Akt pathway has attracted great interest of researchers in the development of anticancer drugs. In this study, fifteen 6-(pyridin-3-yl) quinazolin-4(3H)-one derivatives were designed and synthesized. Anticancer activities of the synthetic compounds were evaluated and the potential mechanisms were explored. Several compounds showed certain proliferation inhibitory activity against the tested cancer cells including human non-small cell lung cancer (NSCLC) HCC827, human neuroblastoma SH-SY5Y and hepatocellular carcinoma LM3 cells. Among them, compound 7i and 7m showed the best inhibitory activity against all the cancer cell lines and more active against HCC827 cells with IC50 values of 1.12 μM and 1.20 μM, respectively. In addition, 7i and 7m showed lower inhibitory activity against H7702 cells (human normal liver cells) with IC50 values of 8.66 μM and 10.89 μM, respectively, nearly 8-fold lower than that in HCC827 cells. These results suggested that compounds 7i and 7m had certain selectivity to tumor cells, compared to human normal cells. Further biological studies indicated 7i induced G2/M phase arrests and cell apoptosis of HCC827 cells via PI3K/Akt and caspase dependent pathway. Together, these novel 6-(pyridin-3-yl) quinazolin-4(3H)-one derivatives such as compound 7i and 7m might be lead compounds for development of potential anti-cancer drugs.
Synthesis and antitumor activity evaluation of PI3K inhibitors containing 3-substituted quinazolin-4(3H)-one moiety
Zhang, Hao,Xin, Min-Hang,Xie, Xiao-Xiao,Mao, Shuai,Zuo, Sai-Jie,Lu, She-Min,Zhang, San-Qi
, p. 7765 - 7776 (2015)
In present study, a series of N-(2-methoxy-5-(3-substituted quinazolin-4(3H)-one-6-yl)-pyridin-3-yl)phenylsulfonamide were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against HCT116 and MCF-7 cancer cell lines. The SAR of title compounds was discussed. The compounds (S)-C5 and (S)-C8 displayed potent inhibitory activity against PI3Ks and mTOR, especially against PI3Kα. In addition, compound (S)-C5 can efficaciously inhibit tumor growth in a mice S-180 model. These findings suggest that our designed compounds can serve as potent PI3K inhibitors and effective anticancer agents.
6 - (Pyridin -3 -yl) quinazoline -4 (3H) - ketone derivative as well as preparation and application thereof
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Paragraph 0057-0058; 0059-0060, (2021/10/05)
The invention discloses 6 - (pyridin -3 -yl) quinazoline -4 (3H) - ketone derivatives, and the structural formula is shown I. The invention also discloses a synthetic method thereof. Anti-tumor activity studies found compounds Ii and Im for human non-small cell lung cancer (NSCLC) HCC827. Human erythrocytes and leukocyte leukemia cells HEL, human neuroblastoma SH-SY5Y and liver cancer LM3 cells all show good proliferation inhibition activity. Ia-Iq all 17 compounds can reverse the drug resistance of Tylin drug-resistant A549/T cells, adriamycin drug-resistant MCF F F F F-7/ADR cells and adriamycin resistance HepG2/ADM cells to the corresponding chemotherapeutic drugs in different degrees.
Pyrido imidazole substituted quinazolinone derivative as well as synthesis method and application thereof
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Paragraph 0069-0071; 0076, (2021/10/16)
The invention discloses a pyridazole substituted quinazolinone derivative, and the structural formula thereof is as follows. The invention also discloses a synthetic method thereof. The pyrido-imidazole-substituted quinazolinone derivative can induce high
6-(2-amino-1H-benzo[d]imidazole-6-yl)quinazoline-4(3H)-one compound
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Paragraph 0041-0044; 0055-0058; 0069-0072; 0083-0086, (2020/01/25)
The invention discloses a 6-(2-amino-1H-benzo[d]imidazole-6-yl)quinazoline-4(3H)-one compound,a preparation method and applications thereof, wherein the structural general formula (I) of the compoundis defined in the specification, R1 is hydrogen atom, morpholinomethyl, piperazinomethyl or substituted piperazinomethyl, R2 is hydrogen atom, butyl, morpholine substituted alkyl, benzyl, substitutedbenzyl, tryptamine, substituted tryptamine or N,N-dimethylamino, R3 is-C(O)R4 or-SO2R5, R4 and R5 are alkyl (C3-C6 alkyl), cycloalkyl (3-6-membered ring), alkoxy or alkyl substituted amino, and n is 1, 2, 3 or 4. The compound of the invention has inhibition activity on breast cancer, prostate cancer and human neuroblastoma.
Selective Oxidative Cleavage of 3-Methylindoles with Primary Amines Affording Quinazolinones
He, Junhui,Dong, Jianyu,Su, Lebin,Wu, Shaofeng,Liu, Lixin,Yin, Shuang-Feng,Zhou, Yongbo
supporting information, p. 2522 - 2526 (2020/04/09)
A selective functionalization of C-C-C bonds toward N-C-O bonds is realized by an n-Bu4NI-catalyzed reaction of 3-methylindoles with primary amines using TBHP as the unique oxidant. The systematic process involves oxygenation, nitrogenation, ring-opening, and recyclization, affording a broad range of quinazolinones in good to excellent yields.
Copper-Catalyzed Oxidative Multicomponent Annulation Reaction for Direct Synthesis of Quinazolinones via an Imine-Protection Strategy
Liang, Yantang,Tan, Zhenda,Jiang, Huanfeng,Zhu, Zhibo,Zhang, Min
supporting information, p. 4725 - 4728 (2019/06/17)
Via an imine-protection strategy, we herein present an unprecedented copper-catalyzed oxidative multicomponent annulation reaction for direct synthesis of quinazolinones. The construction of various products is achieved via formation of three C-N and one
Synthesis and biological evaluation of some amino- and sulfanyl-3H-quinazolin-4-one derivatives as potential anticancer agents
Malinowski, Zbigniew,Fornal, Emilia,Nowak, Monika,Kontek, Renata,Gajek, Gabriela,Borek, Bartlomiej
, p. 1723 - 1731 (2015/09/15)
A series of 6-substituted quinazolinone derivatives were prepared by the reaction of 6-bromoquinazolinones with aryl or alkyl amines and thiols, in the presence of a Pd(OAc)2/Xantphos system, under Buchwald-Hartwig-type reaction conditions. The 6-bromoquinazolinones were obtained in the three-components reaction of 5-bromoisatoic anhydride, triethyl orthoformate and an appropriate amine. Biological screening of the potential cytotoxicity of synthesized compounds on HT29 and HCT116 cell lines, as well as on the lymphocytes, showed that some derivatives of quinazolinone have significant anticancer activities. The detailed synthesis, spectroscopic data, and biological assays were reported.
