13790-39-1Relevant articles and documents
Design, synthesis and biological evaluation of novel histone deacetylase inhibitors incorporating 4-aminoquinazolinyl systems as capping groups
Zhang, Qingwei,Li, Yang,Zhang, Baoyin,Lu, Bingliu,Li, Jianqi
, p. 4885 - 4888 (2017)
A series of hydroxamic acid-based HDACIs with 4-aminoquinazolinyl moieties as capping groups was profiled. Most compounds showed more potent HDACs inhibition activity than clinically used drug SAHA. Among them, compounds 5f and 5h selectively inhibited HDAC 1,2 over HDAC8, and showed strong activity in several cellular assays, not possessing significant toxicity to primary human cells and hERG inhibition. Strikingly, 5f possessed acceptable pharmacokinetic characteristics and exhibited significant antitumor activity in an A549 xenograft model study at well tolerated doses.
Pure red phosphorescent iridium(iii) complexes containing phenylquinazoline ligands for highly efficient organic light-emitting diodes
Tian, Houru,Liu, Di,Li, Jiuyan,Ma, Mengyao,Lan, Ying,Wei, Wenkui,Niu, Rui,Song, Kai
, p. 11253 - 11260 (2021)
Two novel heteroleptic iridium complexes containing 4-phenylquinazoline (pqz) as a cyclometalating ligand, namelyIr1andIr2, are designed and synthesized. Methoxy groups are incorporated into the 6- and 7-sites of pqz rings to tune the physical properties
6,7-Dimethoxy-Quinazolin-4-yl-Amino-Nicotinamide Derivatives as Potent Inhibitors of VEGF Receptor II
Ashok, Abhishek,Thanukrishnan, Kannan,Bhojya Naik, Halehatty S.,Ghosh, Soma
, p. 1723 - 1728 (2017)
The sprouting of new blood vessels, or angiogenesis, is necessary for any solid tumor to grow large enough to cause life-threatening disease. Vascular endothelial growth factor (VEGF) is one of the key promoters of tumor-induced angiogenesis. Inhibition of the VEGF signaling pathway has emerged as one of the most promising new approaches for cancer therapy. A series of 6,7-dimethoxy-quinazolin-4-yl-amino-nicotinamides were synthesized and evaluated as antagonists of VEGF receptor II (VEGFR-2). Many compounds display VEGFR-2 inhibitory activity, and compound 7a was found to be a potent inhibitor of VEGFR-2 in an homogeneous time-resolved fluorescence enzymatic assay with an IC50 as low as 48 nM (comparable activity to ZD-6474).
Pro-apoptotic activity of novel 4-anilinoquinazoline derivatives mediated by up-regulation of bax and activation of poly(ADP-ribose) phosphatase in ehrlich ascites carcinoma cells
Devegowda, Preethi Saligrama,Balaji, Kyathegowdanadoddi Srinivas,Prasanna, Doddakunche Shivaramu,Swaroop, Toreshettahally Ramesh,Jayarama, Shankar,Siddalingaiah, Lokesh,Rangappa, Kanchugarakoppal Subbegowda
, p. 896 - 904 (2017)
Quinazolines are very important class of heterocyclic compounds with antitumor properties. In search of novel anti-tumour agents, a series of 4-anilinoquinazolines were synthesized and characterized using proton and 13C NMR, Fourier transform infrared and mass spectroscopic techniques. These compounds were evaluated for their cytotoxic effect on ehrlich ascites carcinoma cells using MTT assay. Among the tested compounds, compound N-(3-((6,7-dimethoxyquinazoline-4-yl)amino)phenyl)-4-nitrobenzene sulfonamide exhibited more potent activity with an IC50 value of 10.29 ± 1.14 μM against ehrlich ascites carcinoma cell line. in vivo studies using compound N-(3-((6,7-dimethoxyquinazoline-4-yl)amino)phenyl)-4-nitrobenzene sulfonamide (4G) showed that there was reduction in the mice body weight, ascites volume and decrease in cell number. Mice treated with compound 4G showed higher survivability compared with that of control mice. The cells treated with compound 4G also exhibited typical morphological changes of apoptotic damages. Further, compound 4G induced tumour cell death by activating pro-apoptotic protein Bax which activates caspase-3 which in turn cleaves poly (ADP- ribose) polymerase and causes DNA fragmentation. Thus, our results strongly conclude that our compound 4G acts as a antincancer agent by inducing apoptosis in ehrlish ascites carcinoma cells.
Synthesis of [methoxy-11C]PD153035, a selective EGF receptor tyrosine kinase inhibitor
Johnstroem, Peter,Fredriksson, Anna,Thorell, Jan-Olov,Stone-Elander, Sharon
, p. 623 - 629 (1998)
[Methoxy-11C]PD153035, a potent and specific inhibitor of the EGF receptor tyrosine kinase, was prepared by O-alkylation of O-desmethyl PD153035 with [11C]methyl iodide in DMF. The radiochemical incorporation of [11C]CH3I was on the order of 45%. The mean specific activity obtained at end-of-synthesis (EOS) was 26 GBq/μmol (n=3; range 20-36 GBq/μmol) and total synthesis time was 45-50 minutes including formulation.
Synthesis and biological evaluation of novel triazolyl 4-anilinoquinazolines as anticancer agents
Hassan, Hani Mutlak A.,Denetiu, Iuliana,Khan, Salman A.,Rehan, Mohd,Sakkaf, Kaltoom,Gauthaman, Kalamegam
, p. 1766 - 1772 (2019)
The synthesis of novel triazolyl 4-anilinoquinazolines in five sequential synthetic steps via copper-catalyzed click chemistry and their anticancer biological evaluation is described.
Syntheses, antiviral activities and induced resistance mechanisms of novel quinazoline derivatives containing a dithioacetal moiety
Xie, Dandan,Shi, Jing,Zhang, Awei,Lei, Zhiwei,Zu, Guangcheng,Fu, Yun,Gan, Xiuhai,Yin, Limin,Song, Baoan,Hu, Deyu
, p. 433 - 443 (2018)
A series of novel quinazoline derivatives containing a dithioacetal moiety were designed and synthesized, and their structures were characterized by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and high-resolution mass spectrometry. Bioassay results indicated that compound 4b exhibited remarkable protective activity against cucumber mosaic virus (CMV, EC50 = 248.6 μg/mL) and curative activity against potato virus Y (EC50 = 350.5 μg/mL), which were better than those of ningnanmycin (357.7 μg/mL and 493.7 μg/mL, respectively). Moreover, compound 4b could increase the chlorophyll content in plants, improve photosynthesis, and effectively induce tobacco anti-CMV activity.
The preparation and SAR of 4-(anilino), 4-(phenoxy), and 4-(thiophenoxy)-quinazolines: Inhibitors of p56(lck) and EGF-R tyorsine kinase activity
Myers, Michael R.,Setzer, Natalie N.,Spada, Alfred P.,Zulli, Allison L.,Hsu, Chin-Yi J.,Zilberstein, Asher,Johnson, Susan E.,Hook, Linda E.,Jacoski, Mary V.
, p. 417 - 420 (1997)
We report herein our preliminary results of a SAR study of quinazoline-based inhibitors of p56(lck) and EGF-R tyrosine kinase activity. The most potent inhibitor of p56(lck) identified, RPR-108518A (10), has an IC50 of 0.50 μM. The 3-chlorophenoxy- and 3-chlorothiophenoxy- derivatives 5 and 6 were also shown to be extremely potent EGF-R inhibitors.
6-Aryl substituted 4-(4-cyanomethyl) phenylamino quinazolines as a new class of isoform-selective PI3K-alpha inhibitors
Yadav, Rammohan R.,Guru, Santosh K.,Joshi, Prashant,Mahajan, Girish,Mintoo, Mubashir J.,Kumar, Vikas,Bharate, Sonali S.,Mondhe, Dilip M.,Vishwakarma, Ram A.,Bhushan, Shashi,Bharate, Sandip B.
, p. 731 - 743 (2016)
Isoform-selective inhibition of PI3K-α has been identified as one of the important strategy to discover effective and safer anticancer agents. Herein, we report discovery of ‘quinazoline’ as a new chemotype for isoform-selective PI3K-α inhibitors. The indolyl substituted quinazoline 9u displayed selective inhibition of PI3K-α with IC50value of 0.201?μM with >49.7 over PI3K-β, and δ-isoforms. Quinazoline 9u also inhibited PI3K-γ with IC50value of 0.750 μM (3.7 fold selective for α-versus γ-isoform). The isoform-selective inhibition was also demonstrated at protein-expression level by western-blot analysis in MCF-7 and PC-3?cells. The isoform-selective inhibitor 9u also showed inhibition of phospho-Akt levels in these cells. Quinazoline 9u showed in-vitro cytotoxicity in MCF-7?cells with GI50of 7?μM, which was highly selective for cancer cells, as it was non-toxic to normal cells fR2, HEK293 and hGF (GI50?>?50?μM). Compound 9u at 25?mg/kg dose showed 62 and 37% TGI in Ehrlich Ascites Carcinoma and Ehrlich Solid Tumor mice models. In nutshell, our efforts to identify potent and efficacious PI3K inhibitors resulted in the discovery of a new class of isoform-selective PI3K-α inhibitors possessing promising in-vivo anticancer activity.
Epidermal growth factor receptor tyrosine kinase: Structure-activity relationships and antitumour activity of novel quinazolines
Gibson,Grundy,Godfrey,Woodburn,Ashton,Curry,Scarlett,Barker,Brown
, p. 2723 - 2728 (1997)
Investigation of structure-activity relationships of novel quinazolines has identified 4-(4-isoquinolylamino)-quinazoline and a 4-(trans-2-phenylcyclopropylamino)-quinazoline as potent inhibitors of EGF-receptor tyrosine kinase in vitro. Further modificatons of the latter compound have identified a derivative which shows anti-tumour activity against a tumour xenograft model when dosed orally once per day.
