133928-61-7Relevant articles and documents
Synthesis and evaluation of new thiourea derivatives as antitumor and antiangiogenic agents
Bai, Wenjing,Huang, Qiang,Ji, Jianxin,Wei, Wei
supporting information, (2020/09/07)
A series of novel thiourea derivatives were synthesized and evaluated by biological activities. Among them, compound 10e containing 3,5-bis(trifluoromethyl)phenyl moiety (R1) at the terminal thiourea and phenylamino (R2) at the terminal acyl position showed the best cytotoxic activities against seven cancer cell lines (NCI-H460, Colo-205, HCT116, MDA-MB-231, MCF-7, HepG2, PLC/PRF/5) and HUVECs. Moreover, compound 10e moderately inhibited various RTKs such as VEGFR2, VEGFR3, and PDGFRβ. Notably, 10e exhibited much better inhibitory effect of tumor formation and antiangiogenic activities than Sorafenib and Regorafenib at the same concentration. Further docking studies suggested that 10e could serve as potential candidate for cancer therapy.
Discovery of novel picolinamide-based derivatives as novel VEGFR-2 kinase inhibitors: Synthesis,: in vitro biological evaluation and molecular docking
Sun, Wuji,Fang, Shubiao,Yan, Hong
supporting information, p. 1054 - 1058 (2018/06/27)
Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in tumor angiogenesis, and inhibition of the VEGFR-2 signaling pathway has emerged as an attractive target for cancer therapy. In our effort, a novel series of picolinamide-based derivatives were designed and synthesized as potent and effective VEGFR-2 inhibitors. All the newly prepared compounds were evaluated in vitro for their antiproliferative activity against A549 and HepG2 cell lines. Among the new compounds, 8j and 8l exhibited better activity against both A549 and HepG2 cell lines. Molecular docking was performed to investigate the binding capacity and binding mode with VEGFR-2 (PDB code: 4ASD).
Novel Antitubercular 6-Dialkylaminopyrimidine Carboxamides from Phenotypic Whole-Cell High Throughput Screening of a SoftFocus Library: Structure-Activity Relationship and Target Identification Studies
Wilson, Colin R.,Gessner, Richard K.,Moosa, Atica,Seldon, Ronnett,Warner, Digby F.,Mizrahi, Valerie,Soares De Melo, Candice,Simelane, Sandile B.,Nchinda, Aloysius,Abay, Efrem,Taylor, Dale,Njoroge, Mathew,Brunschwig, Christel,Lawrence, Nina,Boshoff, Helena I. M.,Barry, Clifton E.,Sirgel, Frederick A.,Van Helden, Paul,Harris, C. John,Gordon, Richard,Ghidelli-Disse, Sonja,Pflaumer, Hannah,Boesche, Markus,Drewes, Gerard,Sanz, Olalla,Santos, Gracia,Rebollo-Lopez, Maria José,Urones, Beatriz,Selenski, Carolyn,Lafuente-Monasterio, Maria Jose,Axtman, Matthew,Lelièvre, Jo?l,Ballell, Lluis,Mueller, Rudolf,Street, Leslie J.,Ghorpade, Sandeep R.,Chibale, Kelly
supporting information, p. 10118 - 10134 (2018/01/10)
A BioFocus DPI SoftFocus library of ～35 000 compounds was screened against Mycobacterium tuberculosis (Mtb) in order to identify novel hits with antitubercular activity. The hits were evaluated in biology triage assays to exclude compounds suggested to function via frequently encountered promiscuous mechanisms of action including inhibition of the QcrB subunit of the cytochrome bc1 complex, disruption of cell-wall homeostasis, and DNA damage. Among the hits that passed this screening cascade, a 6-dialkylaminopyrimidine carboxamide series was prioritized for hit to lead optimization. Compounds from this series were active against clinical Mtb strains, while no cross-resistance to conventional antituberculosis drugs was observed. This suggested a novel mechanism of action, which was confirmed by chemoproteomic analysis leading to the identification of BCG-3193 and BCG-3827 as putative targets of the series with unknown function. Initial structure-activity relationship studies have resulted in compounds with moderate to potent antitubercular activity and improved physicochemical properties.
