181374-43-6Relevant articles and documents
Discovery of Novel Dihydrothiopyrano[4,3-d]pyrimidine Derivatives as Potent HIV-1 NNRTIs with Significantly Reduced hERG Inhibitory Activity and Improved Resistance Profiles
Wang, Zhao,Zalloum, Waleed A.,Wang, Wenbo,Jiang, Xiangyi,De Clercq, Erik,Pannecouque, Christophe,Kang, Dongwei,Zhan, Peng,Liu, Xinyong
, p. 13658 - 13675 (2021)
Enlightened by the available structural biology information, a novel series of dihydrothiopyrano[4,3-d]pyrimidine derivatives were rationally designedviascaffold hopping and molecular hybridization strategies. Notably, compound 20a yielded exceptionally potent antiviral activities (EC50= 4.44-54.5 nM) against various HIV-1 strains and improved resistance profiles (RF = 0.5-5.6) compared to etravirine and rilpivirine. Meanwhile, 20a exhibited reduced cytotoxicity (CC50= 284 μM) and higher SI values (SI = 5210-63992). Molecular dynamics simulations were performed to rationalize the distinct resistance profiles. Besides, 20a displayed better solubility (sol. = 12.8 μg/mL) and no significant inhibition of the main CYP enzymes. Furthermore, 20a was characterized for prominent metabolic stability andin vivosafety properties. Most importantly, the hERG inhibition profile of 20a (IC50= 19.84 μM) was a remarkable improvement. Overall, 20a possesses huge potential to serve as a promising drug candidate due to its excellent potency, low toxicity, and favorable drug-like properties.
Discovery of thiapyran-pyrimidine derivatives as potential EGFR inhibitors
Chu, Cilong,Xiao, Zhen,Xu, Shan,Yang, Feiyi,Yang, Zunhua,Zhang, Qian,Zheng, Pengwu,Zhou, Lingjia,Zhou, Zhihui,Zhu, Wufu
, (2020)
A series of novel thiapyran-pyrimidine derivatives (10a–10h, 11a–11g, 12a–12f, 13a–13f, 14a–14f) were synthesized and their antiproliferative activities were tested. Most of the target compounds showed good activity on one or more cancer cell lines but low activity on human normal cell LO2. The most promising compound 13a exhibited the similar IC50 values on A549 and H1975 cell lines to the lead drug Olmutinib, and exhibited excellent activity and selectivity on EGFRT790M/L858R in the kinase experiment. AO and Hoechst33258 staining indicated that 13a could effectively induce H1975 cells apoptosis. Cell cycle and apoptosis analysis suggested that 13a could block cancer cells in G2/M phase and induce into late apoptosis in a manner of concentration-dependent. The structure–activity relationship of 13a was analyzed to explore its mechanism. All the results showed that 13a was a promising EGFR inhibitor.
Design, synthesis, biological evaluation and docking studies of novel 2-substituted-4-morpholino-7,8-dihydro-5 H -thiopyrano[4,3- d ]pyrimidine derivatives as dual PI3Kα/mTOR inhibitors
Lei, Fei,Sun, Chengyu,Xu, Shan,Wang, Qinqin,Ouyang, Yiqiang,Chen, Chen,Xia, Hui,Wang, Linxiao,Zheng, Pengwu,Zhu, Wufu
, p. 27 - 35 (2016)
Four series of 2-substituted-4-morpholino- 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives (9-28) were designed, synthesized and their structures were confirmed by 1H NMR, 13C NMR and MS spectrum. All compounds were evaluated for the IC50 values against three cancer cell lines (A549, PC-3 and MCF-7). And four selected compounds (10, 11, 24, 27) were further evaluated for the IC50 values against PI3Kα and mTOR kinases. Seven of the target compounds exhibited moderate to excellent antitumor activities against these three cancer cell lines. The most promising compound 11 showed good antitumor potency for A549, PC-3 and MCF-7 cell lines with IC50 values of 0.52 ± 0.10 1/4M, 1.41 ± 0.10 1/4M, 4.82 ± 0.24 1/4M and moderate antitumor activities against PI3Kα/mTOR with IC50 values of 6.72 ± 0.30 1/4M and 0.94 ± 0.10 1/4M. Structure-activity relationships (SARs) and docking studies indicated that aryl urea scaffolds had a significant impact on the antitumor activities, and aryl pyridine urea scaffolds produced the best potency. Variations in substitutions of the aryl group had a significant impact on the activity and 3-Cl-4-F or 3-CF3-4-Cl substitution was more preferred.
Synthesis and anticancer activity of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety
Sun, Chengyu,Chen, Chen,Xu, Shan,Wang, Jianqiang,Zhu, Yan,Kong, Dejia,Tao, Hong,Jin, Mengjia,Zheng, Pengwu,Zhu, Wufu
, p. 3862 - 3869 (2016)
Herein, we designed and synthesized of a novel series of 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety (10a–j, 13a–j). All the compounds were evaluated for the IC50values against five cancer cell lines (A549, PC-3, MCF-7, Hela and HepG2). Seven of the target compounds exhibited moderate to excellent cytotoxicity. For these compounds, we tested their inhibitory activities against mTOR kinase, and four of them were tested their inhibitory activities against PI3Kα kinase in further. The results indicated that the optimized compound 10j showed excellent inhibitory activity and cytotoxicity against mTOR kinase, PI3Kα kinase and five cancer cell lines with IC50values of 1.1?μM, 0.92?μM and 8.77–14.3?μM. Structure–activity relationships (SARs) and docking studies indicated that the thiopyrano[4,3-d]pyrimidine scaffolds exerted little effect on antitumor activities of target compounds. Substitutions of chromone moiety at C-6 position with carboxyl were benefit to the antitumor activities.
Design, synthesis, anticancer activity and docking studies of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives as mTOR inhibitors
Zhu, Wufu,Sun, Chengyu,Xu, Shan,Wu, Chunjiang,Wu, Jielian,Xu, Mengze,Zhao, He,Chen, Le,Zeng, Weipeng,Zheng, Pengwu
, p. 6746 - 6754 (2014)
A series of 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives (7a-q, 10a-q) were designed, synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR, MS and HRMS spectrum. All the compounds were evaluated for t
2-Aryl-4-aromatic methylaminopyrimidine compounds and their applications
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Paragraph 0057; 0063-0064, (2022/01/12)
The present invention relates to 2- aryl-4-aromatic methylaminopyrimidine compounds shown in general formula I and their applications, wherein substituents X,R1,R2 have the meaning given in the specification. The present invention al
Preparation and application of 2-aminopyrimidine heterocyclic compounds containing 4-acylamino phenoxy
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, (2020/10/14)
The invention relates to preparation and application of 2-aminopyrimidine heterocyclic compounds containing 4-acylamino phenoxy as shown in general formulas I and II, and pharmaceutically acceptable salts, hydrates, solvates and prodrugs of the compounds. Substituents X, R1 and R2 have meanings given in the specification. The compounds shown in the general formulas I and II have a strong effect ofinhibiting EGFR, EGFRT790M/L858R and EGFRT790M kinase; the compounds have very low inhibitory activity on human normal hepatocyte LO2. The invention also relates to application of the compounds and pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof in preparation of drugs for treating diseases caused by abnormal activation and high expression of EGFR kinase and positive mutation of T790M and L858R, particularly application in preparing medicines for treating and/or preventing cancers.
A phenyl acrylamide structure containing substituted pyrimidine compound and use thereof (by machine translation)
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Paragraph 0056; 0097; 0098, (2019/02/10)
The invention discloses a containing substituted phenyl acrylamide structure of the pyridine compound, its geometric isomer and its pharmaceutically acceptable salt, hydrate, solvate or prodrug. The invention containing substituted phenyl acrylamide structure of pyrimidines, and its pharmaceutically acceptable salt, hydrate or solvate thereof as an active ingredient, with a pharmaceutically acceptable carrier or excipient mixed preparation composition in, and prepared into a clinically acceptable dosage form. The compounds of the invention in preparing and treating and/or preventing proliferative disorders application of the medicament, for treating and/or preventing cancer of application of the medicament, for treating and/or preventing lung cancer, prostate cancer, breast cancer and applied in the medicine of cervical cancer. (by machine translation)
Rare aryl amide structure heterocyclic compound and its preparation method and application
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, (2017/08/26)
The invention discloses a biaryl amide structure containing heterocyclopyrimidine compound as well as a geometrical isomer, a pharmaceutically acceptable salt, a hydrate, a solvate or a prodrug and a preparation method of the heterocyclopyrimidine compound. The biaryl amide structure containing heterocyclopyrimidine compound as well as the pharmaceutically acceptable salt, the hydrate or the solvate of the heterocyclopyrimidine compound are taken as active components and mixed with a pharmaceutically acceptable carrier or excipient for preparation of composition and clinically acceptable dosage forms. The invention further discloses applications of the compound to preparation of drugs for treating and/or preventing hyperplastic diseases, preparation of drugs for treating and/or preventing cancer and preparation of drugs for treating and/or preventing prostate cancer, lung cancer and liver cancer.
[...] -containing heterocyclic structure and preparation and application of compound miazines
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, (2016/12/01)
The invention belongs to the field of chemic synthesis and relates to a heterocyclopyrimidine compound containing an aryl hydrazone structure, as well as a stereomer and pharmaceutically acceptable salt, hydrate, solvate or prodrug of the heterocyclopyrim
