253870-02-9Relevant articles and documents
Synthesis, biological evaluation, and in silico study of pyrazoline-conjugated 2,4-dimethyl-1H-pyrrole-3-carboxylic acid derivatives
Rasal, Nishant K.,Sonawane, Rahul B.,Jagtap, Sangeeta V.
, (2020/10/22)
A potential molecular hybridization strategy was used to develop 24 novel pyrazoline-conjugated 2,4-dimethyl-1H-pyrrole-3-carboxylic acid and amide derivatives. The preliminary in vitro antimicrobial assay delivered four potential derivatives with growth inhibition in the range of 50.87–56.60% at the concentration of 32 μg/ml. In the search of an anticancer candidate, all derivatives were screened by NCI-60 at 10 μM concentration, revealing that 12 derivatives were potential agents against the various types of cancer cell lines, with growth inhibition in the range of 50.21–108.37%. The in vitro cytotoxicity assay against the cell line HEK293 (human embryonic kidney cells) and the hemolysis assay of the representative potent compounds propose their potential for a good therapeutic index. In silico studies of the most potent derivatives qualified their significant pharmacokinetic properties with good predicted oral bioavailability and their adherence to Lipinski's rule of five for druglikeness. A molecular docking study against VEGFR-2 with the best-scored conformations reinforced their anticancer potency. The docking study of the most potent compound against VEGFR-2 with the best-scored conformations displayed a binding affinity (?9.5 kcal/mol) comparable with the drug sunitinib (?9.9 kcal/mol) and exhibited that tighter interactions at the active adenosine triphosphate site might be responsible for anticancer potency.
Enhanced fluorescence sensor for targeting recognition of receptor tyrosine kinase and application of fluorescence sensor in cell membrane fluorescence imaging
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, (2019/02/13)
The invention discloses an enhanced fluorescence sensor for targeting recognition of receptor tyrosine kinase and application of the fluorescence sensor in cell membrane fluorescence imaging, and belongs to the technical field of bioluminescence sensing. Effective parts of sunitinib are adopted as recognition groups of the fluorescence sensor SP1, pyrene is adopted as a fluorescent group, and connection is formed through linking groups; and the receptor tyrosine kinase which is protein on cell membranes is abundantly enriched in the process of generation of tumor cells and vessels. The fluorescent sensor SP1 can effectively act on the intracellular domains of the cell membranes of the receptor tyrosine kinase, and compared with amino acids, inorganic salts and other interfering substancesin cells, the fluorescence sensor SP1 exhibits high selectivity and a targeted recognition effect on the receptor tyrosine kinase; the SP1 has good selectivity and high sensitivity in recognition of the receptor tyrosine kinases, fluorescence imaging of the receptor tyrosine kinase can be achieved in the cells, tissue and living bodies, and the enhanced fluorescence sensor has potential application prospects in early cancer diagnosis, visualization therapy and other fields.
Preparation method of sunitinib intermediate
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Page/Page column 4-6, (2019/05/04)
The invention discloses a preparation method of a sunitinib intermediate. The method includes the following steps of 1, synthesis of 2, 4-dimethylpyrrole-3, 5-diethyl dicarboxylate, 2, synthesis of 4-ethoxycarbonyl-3, 5-dimethylpyrrole-2-carboxylic acid, 3, synthesis of 2, 4-dimethyl-3-ethyl pyrrole-2-carboxylate, 4, synthesis of 2, 4-dimethyl-5-aldehyde-1H-pyrrole-3-ethyl formate, and 5, synthesis of 2,4-dimethyl-5-aldehyde-1H-pyrrole-3-carboxylic acid. The method has the advantages that the raw materials are cheap, the environmental pollution is small, the industrial production is easy to achieve, the processing steps are fewer, the operation is simple, the reaction yield is very high, the mass production of enterprise is facilitated, and application and popularization are facilitated.