214470-57-2Relevant articles and documents
Design, synthesis, docking and antitumor activity of quinazolino [3, 4-a] thieno [3, 2-d] pyrimidin-8-one derivatives
Zheng, Youguang,Wu, Xiaoqing,Xue, Bai,Li, Mingdong,Ji, Min
, p. 285 - 290 (2010)
Several novel quinazolino [3, 4-a] thieno [3, 2-d] pyrimidin-8-one derivatives were synthesized. All of the compounds were determined against MiaPaCa2 and DU145 cells in vitro, and the crystal structures of analog 8 and 20 in the active site of the EGFR c
Design, synthesis and biological evaluation of 4-aniline quinazoline derivatives conjugated with hydrogen sulfide (H2S) donors as potent EGFR inhibitors against L858R resistance mutation
An, Lin,Gao, Cai-Yun,Li, Cheng-Lin,Liu, Yi,Meng, Long,Wu, Xiao-Qing,Xu, Liang,Zhang, Ling,Zhang, Wu-Qi,Zheng, You-Guang
, (2020/07/03)
In this study, a series of 4-aniline quinazoline derivatives bearing hydrogen sulfide (H2S) donors were designed, synthesized and evaluated for biological activities. The synthesized compounds were screened for the enzymatic activities against EGFR and EGFR mutants by kinase target-based cell screening method. The results demonstrate that most compounds exhibit selectively inhibitory activities against TEL-EGFR-L858R–BaF3, especially compound 9h with GI50 = 0.008 μM (TEL-EGFR-L858R–BaF3), 0.0069 μM (TEL-EGFR-C797S–BaF3), >10 μM (BaF3), >10 μM (TEL-EGFR-BaF3) and 6.03 μM (TEL-EGFR-T790M-L858R–BaF3). The results from anti-proliferative assays in two NSCLC cell lines indicate that synthetic derivatives (9g, 9h, 15e and 15f) with H2S donor ACS81 display greater anti-proliferative potency against NSCLC cell line H3255 bearing EGFR mutant (L858R) with GI50 values ranging from 0.3486 to 1.348 μM. In addition, compound 9h exhibits weak anti-proliferative effects on other tumor cells (HepG2, MCF-7, HT-29 and A431) and has lower toxic effect on HUVEC cells than AZD9291 (positive control). Meanwhile, compound 9h inhibits the phosphorylation of EGFR in H3255 cells in a dose-dependent manner. Cell cycle analysis reveals that compound 9h suppresses the proliferation of cells by inducing cell cycle arrest in G0-G1 phase. The result of H2S release evaluation suggests that the H2S release of compound 9h is significantly more and faster than other compounds.
Design, synthesis, evaluation and molecular modeling study of 4-N-phenylaminoquinolines for Alzheimer disease treatment
Zhu, Jun,Wang, Li-Ning,Cai, Rong,Geng, Shang-Qi,Dong, Ya-Fei,Liu, Yu-Ming
, p. 1325 - 1329 (2019/04/08)
Dual binding site acetylcholinesterase (AChE) inhibitors and butyrylcholinesterase (BChE) inhibitors have recently emerged as two classes of new anti-Alzheimer agents to positively modify the disease's course. In this work, a new series of 4-N-phenylaminoquinolines was synthesized and evaluated for their abilities to inhibit AChE and BChE. Compound 11b showed significant inhibitory activities on AChE and BChE with IC50 values of 0.86 and 2.65 μM, respectively, a lot better than that of reference drug galanthamine. Furthermore, docking study showed that compound 11b interacted simultaneously not only with active and peripheral sites of AChE, but also with all five regions of BChE active site. These findings suggest that these derivatives could be regarded as promising starting points for further drug discovery developments.
New 4-N-phenylaminoquinoline derivatives as antioxidant, metal chelating and cholinesterase inhibitors for Alzheimer's disease
Cai, Rong,Wang, Li-Ning,Fan, Jing-Jing,Geng, Shang-Qi,Liu, Yu-Ming
, (2019/10/09)
A series of new 4-N-phenylaminoquinoline derivatives were designed, synthesized, and their anticholinesterase activities, 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, metal-chelating ability were tested. Among them, compounds 11j, 11k and 11l had comparable inhibition activities to reference drug galantamine both in AChE and in BChE. Especially, compound 11j revealed the most potent inhibition to eeAChE and eqBChE with IC50 values of 1.20 μM and 18.52 μM, respectively. Furthermore, both kinetic analysis of AChE inhibition and molecular docking study indicated that compound 11j was mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE, and propidium iodide displacement assay showed significant displacement of propidium iodide with compound 11k (25.80%) from PAS of eeAChE. More importantly, compound 11l displayed excellent DPPH radical scavenging activity (84% at 1 mg/mL), and its EC50 value was 0.328 μM. In addition, compounds 11a, 11j, 11k and 11l exhibited obvious biometal chelating abilities toward Al3+, Fe2+, Cu2+ and Zn2+ ions. Taken together, 4-N-phenylaminoquinoline derivatives targeting multiple pathogenetic factors deserve further investigation for treatment of AD.
1,3-disubstituted urea and thiourea derivative and application thereof
-
, (2019/01/23)
The invention discloses a 1,3-disubstituted urea and thiourea derivative and application thereof in the field of pharmaceutical chemistry. A structural formula of the derivative is as shown in the specification, and the derivative gives play to an antitumor function through inhibition of tyrosine protein kinase activity, wherein main tyrosine protein kinase inhibited by the derivative includes c-Met, IGF-1R, Src, c-Kit and the like. The derivative can be used for preparation of medicines for preventing or treating hyperplastic diseases, lung cancers, liver cancers, gastric cancers, colon cancers and breast cancers.
TRICYCLIC COMPOUNDS AS HISTONE METHYLTRANSFERASE INHIBITORS
-
, (2019/03/05)
The present disclosure provides tricyclic compounds of formula (I) that are histone methyltransferases G9a and/or GLP inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of G9a and/or GLP such as cancers and hemoglobi
Synthesis of 4-N-anilinoquinoline compounds and application in preparation of anti-Alzheimer's disease drugs
-
, (2018/04/03)
The invention discloses synthesis of 4-N-anilinquinoline compounds and application in preparation of anti-Alzheimer's disease drugs. The synthesis method comprises taking acetone as a solvent, dissolving 6-methoxy-7-(3-chloropropoxy)-3-nitro-4-N-substituted anilinoquinoline, dropwise adding morpholine, and then performing heating for a reaction, after the reaction is finished, performing cooling to room temperature, and performing drying and purification to obtain the target compound. The 4-N-anilinquinoline compounds include nine kinds of compounds, and the nine kinds of compounds have dual inhibitory activity on acetylcholinesterase and butyrylcholinesterase, have appropriate lipophilicity, can be used to prepare anti-Alzheimer's drugs, and open up a new way for development of novel drugs for treating Alzheimer's disease.
Development of a series of novel 4-anlinoquinazoline derivatives possessing quinazoline skeleton: Design, synthesis, EGFR kinase inhibitory efficacy, and evaluation of anticancer activities in?vitro
Chang, Jin,Ren, Hongyu,Zhao, Mingxia,Chong, Yan,Zhao, Wenwen,He, Yong,Zhao, Yunling,Zhang, Huabei,Qi, Chuanmin
, p. 669 - 688 (2017/07/17)
4-anilinoquinazoline-based derivatives represent an attractive scaffold for small molecular EGFR-TKIs in the field of medicinal chemistry. A series of novel heterocyclic substituted derivatives have been designed, synthesized and evaluated their antitumor
Design and synthesis of a novel photoaffinity probe for labelling EGF receptor tyrosine kinases
Zheng, You-Guang,Wu, Xiao-Qing,Su, Jun,Jiang, Ping,Xu, Liang,Gao, Jian,Cai, Bin,Ji, Min
, p. 954 - 959 (2017/07/24)
The epidermal growth factor receptor (EGFR) and HER2 are two important tyrosine kinases that play crucial roles in signal transduction pathways that regulate numerous cellular functions including proliferation, differentiation, migration, and angiogenesis
HISTONE METHYLTRANSFERASE INHIBITORS
-
, (2017/09/08)
The present disclosure provides certain compounds of formula (I) that are histone methyltransferases G9a and/or GLP inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of G9a and/or GLP such as cancers and hemoglobinpathies such as beta-thalassemia and sickle cell disease. Also provided are pharmaceutical compositions containing such compounds as well as processes and intermediates for preparing such compounds.
