13143-24-3Relevant academic research and scientific papers
Discovery of N-phenyl-(2,4-dihydroxypyrimidine-5-sulfonamido) phenylurea-based thymidylate synthase (TS) inhibitor as a novel multi-effects antitumor drugs with minimal toxicity
Li, Xin-yang,Zhang, Ting-jian,Kamara, Mohamed Olounfeh,Lu, Guo-qing,Xu, Hai-li,Wang, De-pu,Meng, Fan-hao
, (2019/07/16)
Thymidylate synthase (TS) is a hot target for tumor chemotherapy, and its inhibitors are an essential direction for anti-tumor drug research. To our knowledge, currently, there are no reported thymidylate synthase inhibitors that could inhibit cancer cell migration. Therefore, for optimal therapeutic purposes, combines our previous reports and findings, we hope to obtain a multi-effects inhibitor. This study according to the principle of flattening we designed and synthesized 18 of N-phenyl-(2,4-dihydroxypyrimidine-5-sulfonamido)phenyl urea derivatives as multi-effects inhibitors. The biological evaluation results showed that target compounds could significantly inhibit the hTS enzyme, BRaf kinase and EGFR kinase activity in vitro, and most of the compounds had excellent anti-cell viability for six cancer cell lines. Notably, the candidate compound L14e (IC50 = 0.67 μM) had the superior anti-cell viability and safety to A549 and H460 cells compared with pemetrexed. Further studies had shown that L14e could cause G1/S phase arrest then induce intrinsic apoptosis. Transwell, western blot, and tube formation results proved that L14e could inhibit the activation of the EGFR signaling pathway, then ultimately achieve the purpose of inhibiting cancer cell migration and angiogenesis in cancer tissues. Furthermore, in vivo pharmacology evaluations of L14e showed significant antitumor activity in A549 cells xenografts with minimal toxicity. All of these results demonstrated that the L14e has the potential for drug discovery as a multi-effects inhibitor and provides a new reference for clinical treatment of non-small cell lung cancer.
Pyrimidine phenylurea anti-tumor compound and preparation method and application thereof
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Paragraph 0053; 0057, (2018/12/05)
The invention belongs to the field of medicines, and particularly relates to a pyrimidine phenylurea anti-tumor compound and a preparation method and application thereof. A structure general formula of the pyrimidine phenylurea anti-tumor compound is spec
USE OF DDX3X INHIBITORS FOR THE TREATMENT OF PNEUMOVIRUS INFECTIONS
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Page/Page column 30, (2015/10/05)
The invention relates to a DDX3X inhibitorfor use in the treatment of pneumovirus infection in a mammal, wherein the DDX3X inhibitor may be a compound of Formula (I) wherein y, Z, R1, X, L, Ra and Rb are as defined herein.
Discovery of the first small molecule inhibitor of human DDX3 specifically designed to target the RNA binding site: Towards the next generation HIV-1 inhibitors
Radi, Marco,Falchi, Federico,Garbelli, Anna,Samuele, Alberta,Bernardo, Vincenzo,Paolucci, Stefania,Baldanti, Fausto,Schenone, Silvia,Manetti, Fabrizio,Maga, Giovanni,Botta, Maurizio
supporting information; experimental part, p. 2094 - 2098 (2012/04/17)
Efficacy of currently approved anti-HIV drugs is hampered by mutations of the viral enzymes, leading invariably to drug resistance and chemotherapy failure. Recent data suggest that cellular co-factors also represent useful targets for anti-HIV therapy. H
COMPOUNDS WITH DDX3 INHIBITORY ACTIVITY AND USES THEREOF
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Page/Page column 147, (2011/04/25)
The present invention relates to the medical use of the compound of formula 1,2,3 or 4
