928708-60-5Relevant articles and documents
Synthesis, antimycobacterial and anticancer activity of novel indole-based thiosemicarbazones
Mashayekhi, Vida,Haj Mohammad Ebrahim Tehrani, Kamaleddin,Azerang, Parisa,Sardari, Soroush,Kobarfard, Farzad
, (2021/09/08)
Based on the structural elements of bioactive indole-based compounds, a series of novel 1-substituted indole-3-carboxaldehyde thiosemicarbazones were synthesized as potential antimycobacterial and anticancer agents. The derivatives were prepared via a two
Synthesis and antimycobacterial activity of novel thiadiazolylhydrazones of 1-substituted indole-3-carboxaldehydes
Haj Mohammad Ebrahim Tehrani, Kamaleddin,Mashayekhi, Vida,Azerang, Parisa,Sardari, Soroush,Kobarfard, Farzad,Rostamizadeh, Kobra
, p. 224 - 236 (2014/02/14)
A series of novel thiocarbohydrazones of substituted indoles and their corresponding thiadiazole derivatives were prepared, and their structures were confirmed by different analytical and spectroscopic methods. The derivatives were prepared by a sequential synthetic strategy including substitution at N-1 position of indole ring by various aliphatic and benzylic substituents, followed by condensation with thiocarbohydrazide, and finally cyclization by triethyl orthoformate. The derivatives were tested for their antimycobacterial activity against Mycobacterium bovis BCG, and the results revealed that among the synthesized compounds, thiadiazole derivatives 4e, 4f, 4n, 4p, 4q, and 4t exhibited the highest activity with IC50 value of 3.91 μg/mL. The results indicate that the thiadiazole moiety plays a vital role in exerting antimycobacterial activity. A series of indole-based thiadiazole derivatives with various substitutions at N-1 position of indole ring have been synthesized and tested for their antimycobacterial activity. Compounds 4e (R = butyl), 4f (R = pentyl), 4n (R = 4-fluorobenzyl), 4p (R = 4-chlorobenzyl), 4q (R = 4-bromobenzyl) and 4t (R = 4-methoxybenzyl) were the most potent derivatives with IC50 value of 3.91 μg/mL.
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 and structure-activity relationships of potent and selective inhibitors of blood coagulation factor Xa
Ewing, William R.,Becker, Michael R.,Manetta, Vincent E.,Davis, Roderick S.,Pauls, Henry W.,Mason, Helen,Choi-Sledeski, Yong Mi,Green, Daniel,Cha, Don,Spada, Alfred P.,Cheney, Daniel L.,Mason, Jonathan S.,Maignan, Sebastien,Guilloteau, Jean-Pierre,Brown, Karen,Colussi, Dennis,Bentley, Ross,Bostwick, Jeff,Kasiewski, Charles J.,Morgan, Suzanne R.,Leadley, Robert J.,Dunwiddie, Christopher T.,Perrone, Mark H.,Chu, Valeria
, p. 3557 - 3571 (2007/10/03)
The discovery of a series of non-peptide factor Xa (FXa) inhibitors incorporating 3-(s)-amino-2-pyrrolidinone as a central template is described. After identifying compound 4, improvements in in vitro potency involved modifications of the liphophilic group and optimizing the angle of presentation of the amidine group to the S1 pocket of FXa. These studies ultimately led to compound RPR120844, a potent inhibitor of FXa (K1 = 7 nM) which shows selectivity for FXa over trypsin, thrombin, and several fibrinolytic serine proteinases. RPR120844 is an effective anticoagulant in both the rat model of FeCl2-induced carotid artery thrombosis and the rabbit model of jugular vein thrombus formation.