50699-53-1Relevant academic research and scientific papers
Discovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3
Li, Yingxiu,Ye, Tianyu,Xu, Le,Dong, Yuhong,Luo, Yong,Wang, Chu,Han, Yufei,Chen, Ke,Qin, Mingze,Liu, Yajing,Zhao, Yanfang
, (2019/08/12)
Hybridization strategy is an effective strategy to obtain multi-target inhibitors in drug design. In this study, we assembled the pharmacophores of momelotinib and tandutinib to get a series of 4-piperazinyl-2-aminopyrimidine derivatives. All compounds were tested for the inhibition of JAK2 and FLT3 enzymes, of which, compounds with potent enzyme activities were assayed for antiproliferative activities against three cancer cell lines (HEL, MV4-11, and HL60). The structure-activity relationship studies were conducted through variations in two regions, the “A” phenyl ring and “B” phenyl ring. Compound 14j showed the most balanced in vitro inhibitory activity against JAK2 and FLT3 (JAK2 IC50 = 27 nM, FLT3 IC50 = 30 nM), and it also showed potent inhibition against the above tested cell lines. In the cellular context, 14j strongly induced apoptosis by arresting cell cycle in the G1/S phase, and was selected as a promising JAK2/FLT3 dual inhibitor.
Synthesis and antimicrobial activity of novel 1-[3-(1,8-naphthyridin-2-yl)phenyl]-3-arylurea derivatives
Bhasker, G Vijaya,Satyanarayana,Latha,Laxminarayana,Chary, M Thirumala
, p. 771 - 774 (2018/03/13)
2-Aminonicotinaldehyde (1) and 1-(3-nitrophenyl)ethanone (2) react each other in presence of piperidine to form 2-(3-nitrophenyl)-1,8-naphthyridine (3). Compound 3 on reduction with hydrazine hydrate offered 3-(1,8-naphthyridin-2-yl)aniline (4), which on
N-(3,5-dimethyladamantane-1-yl)-N'-substituted phenylurea compound as well as preparation method and application thereof
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Paragraph 0136; 0137, (2017/12/28)
The invention belongs to the technical field of medicinal chemistry, in particular to N-(3,5-dimethyladamantane-1-yl)-N'-substituted phenylurea compounds as well as preparation methods and application thereof. The compounds have the structure shown in the formula I. The compounds are proved that the compounds can improve the image recognition memory, the working and learning memory, the spatial learning and memory ability of model rats and has good anti-alzheimer effects by the new object discrimination experiments, Y-maze experiments, positioning navigation and space exploration experiments in mats. The formula I is shown in the description.
NOVEL UREA DERIVATIVES AS TEC KINASE INHIBITORS AND USES THEREOF
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Page/Page column 53, (2013/03/26)
Provided are urea compounds of formula (I) as Tec kinase inhibitors, in particular ITK (interleukin-2 inducible tyrosine kinase) inhibitors. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders mediated by ITK.
Discovery of CC chemokine receptor-3 (CCR3) antagonists with picomolar potency
De Lucca, George V.,Ui, Tae Kim,Vargo, Brian J.,Duncia, John V.,Santella III, Joseph B.,Gardner, Daniel S.,Zheng, Changsheng,Liauw, Ann,Wang, Zhang,Emmett, George,Wacker, Dean A.,Welch, Patricia K.,Covington, Maryanne,Stowell, Nicole C.,Wadman, Eric A.,Das, Anuk M.,Davies, Paul,Yeleswaram, Swamy,Graden, Danielle M.,Solomon, Kimberly A.,Newton, Robert C.,Trainor, George L.,Decicco, Carl P.,Ko, Soo S.
, p. 2194 - 2211 (2007/10/03)
Starting with our previously described20 class of CC chemokine receptor-3 (CCR3) antagonist, we improved the potency by replacing the phenyl linker of 1 with a cyclohexyl linker and by replacing the 4-benzylpiperidine with a 3-benzylpiperidine. The resulting compound, 32, is a potent and selective antagonist of CCR3. SAR studies showed that the 3-acetylphenyl urea of 32 could be replaced with heterocyclic ureas or heterocyclic-substituted phenyl ureas and still maintain the potency (inhibition of eotaxin-induced chemotaxis) of this class of compounds in the low-picomolar range (IC50 = 10-60 pM), representing some of the most potent CCR3 antagonists reported to date. The potency of 32 for mouse CCR3 (chemotaxis IC50 = 41 nM) and its oral bioavailability in mice (20% F) were adequate to assess the efficacy in animal models of allergic airway inflammation. Oral administration of 32 reduced eosinophil recruitment into the lungs in a dose-dependent manner in these animal models. On the basis of its overall potency, selectivity, efficacy, and safety profile, the benzenesulfonate salt of 32, designated DPC168, entered phase I clinical trials.
