13142-01-3

Upstream product

• 100-28-7 4-Nitrophenyl isocyanate 
• 108-42-9 3-chloro-aniline 
• 50625-49-5 m-Chlorobenzoyl azide 
• 100-01-6 4-nitro-aniline 
• 2733-41-7 4-nitrobenzoyl azide 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 2909-38-8 m-chlorophenyl isocyanate 
• 619-50-1 4-nitrobenzoic acid methyl ester 
• 636-97-5 N-amino-(4-nitrophenyl)carboxamide 

Downstream Products

• 926194-05-0 3-(4-aminophenyl)-(3-chlorophenyl)urea 
• 1416274-94-6 C₁₅H₁₃Cl₂N₃O₂ 
• 1416274-97-9 N-(4-(3-(3-chlorophenyl)ureido)phenyl)-2-(piperazin-1-yl)acetamide 
• 1416275-00-7 C₂₃H₂₈ClN₅O₄ 
• 1416275-03-0 N-(4-(3-(3-chlorophenyl)ureido)phenyl)-2-(4-(2-hydrazinyl-2-oxoethyl)piperazin-1-yl)acetamide 
• 1627523-18-5 1-(3-chlorophenyl)-3-(4-((6-nitroquinoxalin-2-yl)amino)phenyl)urea 

Relevant 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

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.

Design, synthesis and evaluation of acridine derivatives as multi-target Src and MEK kinase inhibitors for anti-tumor treatment

Clinical studies have shown enhanced anticancer effects of combined inhibition of Src and MEK kinases. Development of multi-target drugs against Src and MEK is of potential therapeutic advantage against cancers. As a follow-up of our previous studies, and by using molecular docking method, we designed and synthesized a new series of 9-anilinoacridines containing phenyl-urea moieties as potential novel dual Src and MEK inhibitors. The anti-proliferative assays against K562 and HepG-2 tumor cells showed that most of the derivatives displayed good cytotoxicity in vitro. In particular, kinase inhibition assays showed that compound 8m inhibited Src (59.67%) and MEK (43.23%) at 10 μM, and displayed moderate inhibitory activity against ERK and AKT, the downstream effectors of both Src and MEK. Moreover, compound 8m was found to induce K562 cells apoptosis. Structure-activity relationships of these derivatives were analyzed. Our study suggested that acridine scaffold, particularly compound 8m, is of potential interest for developing novel multi-target Src and MEK kinase inhibitors.

Increasing the binding affinity of VEGFR-2 inhibitors by extending their hydrophobic interaction with the active site: Design, synthesis and biological evaluation of 1-substituted-4-(4-methoxybenzyl)phthalazine derivatives

A series of anilinophthalazine derivatives 4a-j was initially synthesized and tested for its VEGFR-2 inhibitory activity where it showed promising activity (IC50 = 0.636-5.76 μM). Molecular docking studies guidance was used to improve the binding affinity for series 4a-j towards VEGFR-2 active site. This improvement was achieved by increasing the hydrophobic interaction with the hydrophobic back pocket of the VEGFR-2 active site lined with the hydrophobic side chains of Ile888, Leu889, Ile892, Val898, Val899, Leu1019 and Ile1044. Increasing the hydrophobic interaction was accomplished by extending the anilinophthalazine scaffold with a substituted phenyl moiety through an uriedo linker which should give this extension the flexibility required to accommodate itself deeply into the hydrophobic back pocket. As planned, the designed uriedo-anilinophthalazines 7a-i showed superior binding affinity than their anilinophthalazine parents (IC50 = 0.083-0.473 μM). In particular, compounds 7g-i showed IC50 of 0.086, 0.083 and 0.086 μM, respectively, which are better than that of the reference drug sorafenib (IC50 = 0.09 μM).

Synthesis and cytotoxic activity of biphenylurea derivatives containing indolin-2-one moieties

In our endeavor towards the development of potent anticancer agents, two different sets of biphenylurea-indolinone conjugates, 5a-s and 8a,b were synthesized. The in vitro cytotoxicity of the synthesized compounds was examined in two human cancer cell lin

Synthesis and in vitro antiproliferative activity of novel pyrazolo[3,4-d]pyrimidine derivatives

A novel series of pyrazolo[3,4-d]pyrimidine derivatives were designed, synthesized and evaluated for their antiproliferative activity. Among the five compounds selected by NCI, compound 11a showed a distinctive pattern of selectivity on cell line panels and was further screened for a 5-log dose range, where it showed potent antiproliferative activity with median growth inhibition (GI50) equal to 1.71 μM against the CNS cancer SNB-75 cell line. The tested derivative showed remarkably the highest cell growth inhibition against non-small cell lung cancer HOP-62, CNS cancer SNB-75, breast cancer HS578T, and melanoma MALME-3M cell lines. Flow cytometric analysis revealed that compound 11a could significantly induce apoptosis in A549 cells in vitro at low micromolar concentrations. Further investigation showed that compound 11a induced significant cell cycle arrest at G0/G1 phase partly due to its ability to downregulate cyclin D1 and upregulate p27kip1 levels.

Indoline ureas as potential anti-hepatocellular carcinoma agents targeting VEGFR-2: Synthesis, in vitro biological evaluation and molecular docking

In our effort to develop potent and effective agents with anti-proliferative activity towards HepG2 hepatocellular carcinoma cells with potential inhibitory activity against VEGFR-2, a novel series of 1-(4-((2-oxoindolin-3-ylidene)amino)phenyl)-3-arylurea

Design, synthesis and biological evaluation of type-II VEGFR-2 inhibitors based on quinoxaline scaffold

In an effort to develop ATP-competitive VEGFR-2 selective inhibitors, a series of new quinoxaline-based derivatives was designed and synthesized. The target compounds were biologically evaluated for their inhibitory activity against VEGFR-2. The design of the target compounds was accomplished after a profound study of the structure activity relationship (SAR) of type-II VEGFR-2 inhibitors. Among the synthesized compounds, 1-(2-((4-methoxyphenyl)amino)-3- oxo-3,4 dihydroquinoxalin-6-yl)-3-phenylurea (VIIa) displayed the highest inhibitory activity against VEGFR-2. Molecular modeling study involving molecular docking and field alignment was implemented to interpret the variable inhibitory activity of the newly synthesized compounds.

Design, synthesis and anticancer activities of diaryl urea derivatives bearing N-acylhydrazone moiety

A new series of diaryl urea derivatives bearing N-acylhydrazone moiety were designed and synthesized. All the target compounds were evaluated for their cytotoxic activities in vitro against human lung adenocarcinoma epithelial cell line (A549), human breast cancer cell line (MDA-MB-231) and human leukemia cell line (HL-60) by standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Several compounds (1a, 1f and 1h) were further evaluated against human embryonic fibroblast, lung-derived cell line (WI38). The pharmacological results indicated that some compounds exhibited promising anticancer activities. In particular, compound 1f showed the most potent cytotoxicity against the tested three cell lines with IC50 values of 0.41 μM, 0.24 μM and 0.23 μM, respectively.

Nucleophilic Substitutions at Carbonic Acid Derivatives. XX. Aminolysis of Bis(trichlormethyl)carbonate

The rate constants for the two steps of the reaction of bis(trichlormethyl)carbonate with substituted anilines have been determinated by conductivity measurements.The first relatively fast step of the reaction is the nucleophilic attack of the amine to the bis(trichloromethyl)carbonate leading to trichloromethylurethane through a six or four centers transition state in wich the carbon-nitrogen bond is formed parallel with the transfer of the proton.In this reaction a phosgene molecule is also produced, which reacts very fast with amine to form a N,N'-diarylurea.The s econd, much slower step, is the nucleophilic attack of the amine to the trichloromethylurethane.Through a similar transition state in which the proton transfer has even a higher importance, a N,N'-disubstituted urea and an other molecule of phosgene are formed.