61343-99-5Relevant articles and documents
Design, synthesis and structure-activity relationship study of novel urea compounds as FGFR1 inhibitors to treat metastatic triple-negative breast cancer
Akwii, Racheal,Alvina, Karina,Ashraf-Uz-Zaman, Md,Farshbaf, Mohammad Jodeiri,German, Nadezhda A.,Kallem, Raja Reddy,Mikelis, Constantinos M.,Putnam, William,Sajib, Md Sanaullah,Shahi, Sadisna,Trippier, Paul C.,Wang, Wei,Zhang, Ruiwen
supporting information, (2020/10/12)
Triple-negative breast cancer (TNBC) is an aggressive type of cancer characterized by higher metastatic and reoccurrence rates, where approximately one-third of TNBC patients suffer from the metastasis in the brain. At the same time, TNBC shows good responses to chemotherapy, a feature that fuels the search for novel compounds with therapeutic potential in this area. Recently, we have identified novel urea-based compounds with cytotoxicity against selected cell lines and with the ability to cross the blood-brain barrier in vivo. We have synthesized and analyzed a library of more than 40 compounds to elucidate the key features responsible for the observed activity. We have also identified FGFR1 as a molecular target that is affected by the presence of these compounds, confirming our data using in silico model. Overall, we envision that these compounds can be further developed for the potential treatment of metastatic breast cancer.
Computational study and synthesis of a new class of anticonvulsants with 6 Hz psychomotor seizure test activity: 2-(1,3-benzodioxol-5-yloxy)-N'-[substituted]-acetohydrazides
Kumar, Praveen,Tripathi, Laxmi
, p. 1175 - 1193 (2021/12/21)
Background: About 50 million epileptic cases worldwide and 12 million in India are re-ported. Currently, available drugs yield adequate control of seizure in 60-70% of patients and show many toxic effects. These actualities provoked the search for novel, more efficacious and safer anti-convulsants. Objective: The concatenation of 2-(1,3-benzodioxol-5-yloxy)-N'-[substituted]-acetohydrazides SA 1-10 was designed by molecular hybridization, optimized by computational study and synthesized with the objective of obtaining a prototype of potent anticonvulsant molecules especially active against partial seizures. Methods: Computational study was performed to calculate the pharmacophoric design, projection of the pharmacokinetic parameters and docking scores of the titled compounds with molecular targets of epilepsy. The anticonvulsant activity was ascertained by 6 Hz psychomotor seizure test. Minimal motor impairment showing neurotoxicity was assessed using the Rotarod test. Results: Titled compounds possessed the indispensable elements of pharmacophore and displayed good binding affinity with molecular targets of epilepsy, such as GABA (A) alpha-1 & delta receptor, glutamate receptor, Na+/H+ exchanger and GABA-aminotransferase in docking studies. The most potent compound of the concatenation was 2-(1,3-benzodioxol-5-yloxy)-N'-[4-(4-chlorophenoxy)benzylidene]-acetohydrazide SA 4, showing 100% protection at four different time points with ED50 value 146.8 mg/kg at a TPE of 1 h in mice. Conclusion: The protection shown in 6 Hz test is implicated as the compound's ability to control partial seizures. Thus, the titled compounds can be considered as potential prototype candidates for antiepileptic therapy against partial seizures.
Chlorination of Conjugated Nitroalkenes with PhICl 2and so 2Cl 2for the Synthesis of α-Chloronitroalkenes
Fadeeva, Anastasia A.,Ioffe, Sema L.,Tabolin, Andrey A.
supporting information, p. 2679 - 2688 (2020/11/02)
Chlorination of conjugated nitroalkenes with iodobenzene dichloride or sulfuryl chloride to give target α-chloronitroalkenes in good yields is described. Details of the procedure depend on the donating ability of the nitroalkene substituents. The activity of the described chlorinating agents increases in order 'PhICl 2/Py' 2Cl 2' 2Cl 2/HCl' with the former producing the best yields for highly donating substrates and the latter for non-activated groups. An autocatalytic role of hydrogen chloride and the chemoselectivity of chlorination were also demonstrated.
