340319-18-8Relevant articles and documents
Synthesis and anti-proliferative activity of aromatic substituted 5-((1-benzyl-1H-indol-3-yl)methylene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H) -trione analogs against human tumor cell lines
Madadi, Nikhil Reddy,Penthala, Narsimha Reddy,Janganati, Venumadhav,Crooks, Peter A.
, p. 601 - 603 (2014/01/23)
Based on previous SAR studies on N-benzylindole and barbituric acid hybrid molecules, we have synthesized a series of aromatic substituted 5-((1-benzyl-1H-indol-3-yl)methylene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H) -trione analogs (3a-i) and evaluated th
New nucleotide-competitive non-nucleoside inhibitors of terminal deoxynucleotidyl transferase: Discovery, characterization, and crystal structure in complex with the target
Costi, Roberta,Cuzzucoli Crucitti, Giuliana,Pescatori, Luca,Messore, Antonella,Scipione, Luigi,Tortorella, Silvano,Amoroso, Alessandra,Crespan, Emmanuele,Campiglia, Pietro,Maresca, Bruno,Porta, Amalia,Granata, Ilaria,Novellino, Ettore,Gouge, Jéro?me,Delarue, Marc,Maga, Giovanni,Di Santo, Roberto
supporting information, p. 7431 - 7441 (2013/10/21)
Terminal deoxynucletidyl transferase (TdT) is overexpressed in some cancer types, where it might compete with pol μ during the mutagenic repair of double strand breaks (DSBs) through the nonhomologous end joining (NHEJ) pathway. Here we report the discove
Design, synthesis and anticancer activity of 4-morpholinothieno[3,2-d]- pyrimidine derivatives bearing arylmethylene hydrazine moiety
Zhu, Wufu,Zhai, Xin,Fu, Qiangqiang,Guo, Fei,Bai, Mei,Wang, Jianqiang,Wang, Haiyan,Gong, Ping
experimental part, p. 1037 - 1045 (2012/10/08)
Three series of 4-morpholinothieno[3,2-d]pyrimidine derivatives containing arylmethylene hydrazine moiety (11a-f, 13a-k and 15a-h) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. The synthesized compounds were evaluated for their cytotoxicity against three cancer cell lines (H460, HT-29, MDA-MB-231). Most of them exhibited moderate to significant cytotoxicity and high-selectivity against one or more cell lines, especially compounds 11c, 13b, 15f and 15g possessing dramatically increased cytotoxicity as compared with the positive controls, which were further evaluated for six other cancer cell lines and one normal cell line. The most promising compound 11c, bearing 3,4-methylenedioxy phenyl group, showed remarkable cytotoxicity against H460, HT-29 and MDA-MB-231 cell lines with IC50 values of 0.003 μM, 0.42 μM and 0.74 μM, which was 1.6- to 290-fold more potent than GDC-0941.
Design, synthesis and 3D-QSAR analysis of novel 2-hydrazinyl-4- morpholinothieno[3,2-d]pyrimidine derivatives as potential antitumor agents
Zhu, Wufu,Liu, Yajing,Zhai, Xin,Wang, Xiao,Zhu, Yan,Wu, Di,Zhou, Hongyu,Gong, Ping,Zhao, Yanfang
, p. 162 - 175 (2013/01/15)
A series of 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidine derivatives were synthesized and evaluated for their cytotoxic activities against five cancer cell lines. Most of them exhibited moderate to significant cytotoxic activities and high-selectivity against one or more cell lines, and nearly all of them had higher potency than positive controls against MDA-MB-231 cell line. The most promising compound 15f showed strong cytotoxic activities against H460, HT-29 and MDA-MB-231 cell lines, which were 1.7- to 66.5-folds more active than 2-(1H-Indazol-4-yl)-6-((4-(methylsulfonyl)-1-piperazinyl)methyl)-4-(4- morpholinyl)thieno[3,2-d]pyrimidine(GDC-0941). To investigate the SARs of thieno[3,2-d]pyrimidine derivatives in more details, CoMFA (q2 = 0.436, r2 = 0.937) and CoMSIA (q2 = 0.706, r2 = 0.947) models on H460 cell line were established. The generated 3D-QSAR models can be used for further rational design of novel thienopyrimidines as highly potent and selective cytotoxic agents.
Synthesis and biological evaluation of novel 6-hydrazinyl-2,4-bismorpholino pyrimidine and 1,3,5-triazine derivatives as potential antitumor agents
Zhu, Wufu,Liu, Yajing,Zhao, Yanfang,Wang, Haiyan,Tan, Li,Fan, Weijie,Gong, Ping
, p. 812 - 821,10 (2020/09/09)
A series of 6-hydrazinyl-2,4-bismorpholino pyrimidine and 1,3,5-triazine derivatives (5a-5l and 8a-8o) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. All the synthesized compounds were evaluated for antiproliferative activity against three cancer cell lines (H460, HT-29, and MDA-MB-231). Several potent compounds were further evaluated against two other cell lines (U87MG, H1975). Most of the prepared compounds, particularly compounds 5c and 5j with IC50 values (0.07 and 0.05 μM, respectively) in the nM range, exhibited moderate to excellent antiproliferative activity and high selectivity against the H460 cancer cell line as compared with compound 1. The most promising compound 5j, possessing a cyano group at the 3-position of the benzene ring, showed strong antiproliferative activity against H460, HT-29, and MDA-MB-231 cell lines with IC50 values of 0.05, 6.31, and 6.50 μM, which were 4.6- to 190.4-fold more active than compound 1 (9.52, 29.24, and 36.21 μM), respectively. Copyright
Design, synthesis and biological evaluation of thiazole- and indole-based derivatives for the treatment of type II diabetes
Xu, Qinyuan,Huang, Li,Liu, Juan,Ma, Liang,Chen, Tao,Chen, Jinying,Peng, Fei,Cao, Dong,Yang, Zhuang,Qiu, Neng,Qiu, Jingxiang,Wang, Guangcheng,Liang, Xiaolin,Peng, Aihua,Xiang, Mingli,Wei, Yuquan,Chen, Lijuan
experimental part, p. 70 - 81 (2012/07/30)
Present studies have shown that the lipid carrier has a significant role in several aspects of metabolic syndrome in A-FABP/ap2-deficient mice, including type 2 diabetes and atherosclerosis. 38 Thiazole- and indole-based derivatives were synthesized and investigated for their inhibitory effects on the production of LPS-stimulated TNF-α. Among them, 12b exhibited an excellent inhibitory efficiency compared to BMS309403 (95% vs. 85%) at the concentration of 10 μM and a binding affinity for ap2 with the apparent Ki values 33 nM. Oral administration of 12b at a dosage of 50 mg/kg effectively reduced the levels of plasma blood glucose, triglycerides, insulin, total cholesterol and alanine aminotransferase in high-fat/diet-induced obesity model. The results highlighted that 12b was a potent anti-diabetic agent.
Synthesis and in vitro screening of novel N-benzyl aplysinopsin analogs as potential anticancer agents
Penthala, Narsimha Reddy,Yerramreddy, Thirupathi Reddy,Crooks, Peter A.
scheme or table, p. 1411 - 1413 (2011/04/23)
A series of novel substituted (Z)-5-((1-benzyl-1H-indol-3-yl)methylene) imidazolidin-2,4-diones (3a-f) and (Z)-5-((1-benzyl-1H-indol-3-yl)methylene)-2- iminothiazolidin-4-ones (3g-o) have been synthesized utilizing microwave irradiation. These analogs wer
Novel substituted (Z)-5-((N-benzyl-1H-indol-3-yl)methylene)imidazolidine-2,4-diones and 5-((N-benzyl-1H-indol-3-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-triones as potent radio-sensitizing agents
Reddy, Y. Thirupathi,Sekhar, Konjeti R.,Sasi, Nidhish,Reddy, P. Narsimha,Freeman, Michael L.,Crooks, Peter A.
scheme or table, p. 600 - 602 (2010/04/26)
A series of (Z)-5-((N-benzyl-1H-indol-3-yl)methylene)imidazolidine-2,4-dione (9a-9m) and 5-((N-benzyl-1H-indol-3-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-trione (10a-10i) derivatives that incorporate a variety of aromatic substituents in both the indole and N-benzyl moieties have been synthesized. These analogs were evaluated for their radiosensitization activity against the HT-29 cell line. Three analogs, 10a, 10b, and 10c were identified as the most potent radiosensitizing agents.
Microwave assisted synthesis and in vitro cytotoxicities of substituted (Z)-2-amino-5-(1-benzyl-1H-indol-3-yl)methylene-1-methyl-1H-imidazol-4(5H)-ones against human tumor cell lines
Penthala, Narsimha Reddy,Yerramreddy, Thirupathi Reddy,Crooks, Peter A.
scheme or table, p. 591 - 593 (2010/04/05)
The synthesis of several novel substituted (Z)-2-amino-5-(1-benzyl-1H-indol-3-yl)methylene-1-methyl-1H-imidazol-4(5H)-ones structurally related to aplysinopsin have been carried out under microwave irradiation and conventional heating methods. The analogs 3a, 3b, 3d-3g, 3k and 3l were evaluated for their in vitro cytotoxic activity against an NCI 60 human tumor cell line panel. Compound 3f exhibited good growth inhibitory properties against all but four of the human cancer cell lines examined, and afforded LC50 values a cytotoxic agent. Thus, the aplysinopsin analog 3f was regarded as a useful lead compound for further structural optimization.
Aplysinopsin analogs: Synthesis and anti-proliferative activity of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-diones
Thirupathi Reddy,Narsimha Reddy,Koduru, Srinivas,Damodaran, Chendil,Crooks, Peter A.
scheme or table, p. 3570 - 3574 (2010/07/17)
A series of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-dione (3) analogs structurally related to aplysinopsin, and that incorporate a variety of substituents in both the indole and N-benzyl moieties have been synthesized under microwave irradiation and conventional heating methods These analogs were evaluated for their anti-proliferative activity against MCF-7 and MDA-231 breast cancer cell lines, and A549 and H460 lung cancer cell lines. Two analogs, 3f and 3j had IC50 values of 4.4 and 5.2 μM, respectively, compared to 5-fluorouracil (IC50 = 15.2 μM) against MCF-7 cells.
