Xn:Harmful;17227-47-3Relevant articles and documents
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.
Synthesis and in vitro anti-bladder cancer activity evaluation of quinazolinyl-arylurea derivatives
Chen, Jia-Nian,Li, Ting,Cheng, Li,Qin, Tai-Sheng,Sun, Ye-Xiang,Chen, Chu-Ting,He, Yue-Zhen,Liu, Guang,Yao, Di,Wei, Ying,Li, Qiu-Yin,Zhang, Guang-Ji
, (2020/09/09)
Based on the structural modification of molecular-targeted agent sorafenib, a series of quinazolinyl-arylurea derivatives were synthesized and evaluated for their anti-proliferative activities against six human cancer cell lines. Compared with other cell lines tested, T24 was more sensitive to most compounds. Compound 7j exhibited the best profile with lower IC50 value and favorable selectivity. In this study, we focused on 7j-induced death forms of T24 cells and tried to elucidate the reason for its potent proliferative inhibitory activity. Compound 7j treatment could trigger three different cell death forms including apoptosis, ferroptosis, and autophagy; which form would occur depended on the concentrations and incubation time of 7j: (1) Lower concentrations within the initial 8 h of 7j treatment led to apoptosis-dependent death. (2) Ferroptosis and autophagy occurred in the case of higher concentrations combining with extended incubation time through effectively regulating the Sxc?/GPx4/ROS and PI3K/Akt/mTOR/ULK1 pathways, respectively. (3) The above death forms were closely associated with intracellular ROS generation and decreased mitochondrial membrane potential induced by 7j. In molecular docking and structure-activity relationship analyses, 7j could bind well to the active site of the corresponding receptor glutathione peroxidase 4 (GPx4). Compound 7j could be a promising lead for molecular-targeted anti-bladder cancer agents’ discovery.
Design, Synthesis, Antiviral Activities of Novel Phosphonate Derivatives Containing Quinazoline Based on Chalone Motif
Zhang, Guo-Ping,Pan, Jian-Ke,Zhang, Jian,Wu, Zeng-Xue,Liu, Deng-Yue,Zhao, Lei
, p. 2548 - 2555 (2017/07/25)
Based on the structure of natural product chalone, a series of novel phosphonate derivatives were designed and synthesized through 1,4-hydrophosphinylation of α,β-unsaturated carbonyl compounds. Their structures were characterized by IR, NMR, MS, and elemental analysis. The antiviral activities against cucumber mosaic virus were evaluated for the first time. The bioassay results indicated that most compounds exhibited good protective activities, low curative activities, and weak inactive activities. The antiviral protective activities of compounds C2 and C5 were 55.1% and 56.8%, respectively, which are slightly higher than those of the commercial Ningnanmyin (49.3%) and Dufulin (53.1%). Moreover, compounds C2 and C9 exhibited moderate curative activities (42.6% and 46.6%). Therefore, the basic motif of C1 can be used as a new lead structure for developing antivirus agents.
Design, synthesis, and biological evaluation of novel quinazolinyl-diaryl urea derivatives as potential anticancer agents
Chen, Jia-Nian,Wang, Xian-Fu,Li, Ting,Wu, De-Wen,Fu, Xiao-Bo,Zhang, Guang-Ji,Shen, Xing-Can,Wang, Heng-Shan
, p. 12 - 25 (2015/11/17)
Through a structure-based molecular hybridization approach, a series of novel quinazolinyl-diaryl urea derivatives were designed, synthesized, and screened for their in vitro antiproliferative activities against three cancer cell lines (HepG2, MGC-803, and A549). Six compounds (7g, 7m, 7o, 8e, 8g, and 8m) showed stronger activity against a certain cell line compared with the positive reference drugs sorafenib and gefitinib. Among the six compounds, 8g exhibited the strongest activity. In particular, compound 8g induced A549 apoptosis, arrested cell cycle at the G0/G1 phase, elevated intracellular reactive oxygen species level, and decreased mitochondrial membrane potential. This compound can also effectively regulate the expression of apoptosis- and cell cycle-related proteins, and influence the Raf/MEK/ERK pathway. Molecular docking and structure-activity relationship analyses revealed that it can bind well to the active site of the receptor c-Raf, which was consistent with the biological data. Therefore, compound 8g may be a potent antitumor agent, representing a promising lead for further optimization.
COMPOUND HAVING TGF-BETA INHIBITORY ACTIVITY AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
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Page/Page column 48, (2010/11/24)
The present invention provides compounds of formula (I) or compounds of formula (II) and pharmaceutically acceptable salts or solvates thereof. An objective of the present invention is to provide compounds having TGF2 inhibitory activity.
PROCESS FOR PRODUCING QUINAZOLIN-4-ONE AND DERIVATIVE THEREOF
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Page 5, (2008/06/13)
A process for preparing quinazolin-4-one or its derivative by reacting anthranilic acid or its derivative with formic acid or its derivative in the presence of ammonia, or by reacting ammonium anthranilate or its derivative with formic acid or its derivative.
CXCR3 antagonists
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, (2008/06/13)
Compounds, compositions and methods that are useful in the treatment of inflammatory and immune conditions and diseases are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of a chemokine receptor. The subject methods are useful for the treatment of inflammatory and immunoregulatory disorders and diseases, such as multiple sclerosis, rheumatoid arthritis and type I diabetes.
Investigation on the photoreactions of nitrate and nitrite ions with selected azaarenes in water
Beitz, Toralf,Bechmann, Wolfgang,Mitzner, Rolf
, p. 351 - 361 (2007/10/03)
The photoreactions of selected azaarenes with nitrate and nitrite ions were investigated under irradiation at λ = 313 nm. The excitation of both anions leads to several photochemical reactions forming mainly hydroxyl radicals and nitrogen oxides. The purification capability of natural waters i.e. the oxidation of inorganic and organic substances results from the formation of hydroxyl radicals. Nitrated isomers of azaarenes were found among the main products of the investigated photoreactions. The nitrogen oxides were responsible for the production of nitrated derivatives which possess a high toxic potential. Their formation was explained by the parallel occurance of two mechanism, a molecular and a radical one. The molecular mechanism became more important with increasing ionisation potentials of the azaarenes. The spectrum of oxidized products corresponded to the one got in the photoreactions of azaarenes with hydrogen peroxide. The formation of several oxidation and nitration products of the pyridine ring with its low electron density was explained by the reaction of excited states of azaarenes. The photoreactions with nitrite ions only led to the formation of oxidized and nitrated products. Nitroso products were not formed. The reactivity of nitrogen monoxide is too low for its reaction with the azaarenes.
Oxidation of substituted 2-thiouracils and pyrimidine-2-thione with ozone and 3,3-dimethyl-1,2-dioxirane
Claudia, Crestini,Mincione, Enrico,Saladino, Raffaele,Nicoletti, Rosario
, p. 3259 - 3272 (2007/10/02)
Ozone and 3,3-dimethyl-1,2-dioxirane react with substituted 2-thiouracils and pyrimidine-2-thione to afford several interesting desulfurized products. The effect of the solvent, protic as opposed to nonprotic, on the course of oxidation was striking.
Anti-tumor compounds
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, (2008/06/13)
The invention relates to quinazoline derivatives, or pharmaceutically-acceptable salts thereof, which possess anti-tumour activity; to processes for their manufacture; and to pharmaceutical compositions containing them. The invention provides a quinazoline of the formula: STR1 wherein R1 includes hydrogen, amino and alkyl or alkoxy each of up to 4 carbon atoms; R2 includes hydrogen, alkyl, hydroxyalkyl and halogenoalkyl each of up to 4 carbon atoms; R3 is hydrogen or alkyl or up to 3 carbon atoms; Ar is phenylene or heterocyclene; L is a group of the formula --CO.NH--, --NH.CO--, --CO.NR4 --, --NR4.CO--, --CH=CH-- or --CO.O--, wherein R4 is alkyl of up to 4 carbon atoms; and Y is a branched alkyl group bearing substituents Y2 and Y3 the definition of each independently including hydroxy, cyano, aryl and heteroaryl, and the definition of Y3 also optionally including sulpho, N-phenylsulphonylcarbamoyl and 5-tetrazolyl; or a pharmaceutically-acceptable salt thereof.
