osimertinib has been researched along with pyrimidine* in 4 studies
4 other study(ies) available for osimertinib and pyrimidine
| Article | Year |
|---|---|
Design, synthesis and biological evaluation of novel 2,4-diaryl pyrimidine derivatives as selective EGFR
Lung cancer is the leading cause of cancer deaths. It has been demonstrated that epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) are efficacious in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). In this work, a new series of 2,4-diaryl pyrimidine derivatives containing cyclopropyl moiety were designed, synthesized and evaluated as novel selective EGFR Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Design; ErbB Receptors; Humans; Male; Mice; Mice, Nude; Models, Molecular; Molecular Structure; Neoplasms, Experimental; Protein Kinase Inhibitors; Pyrimidines; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship | 2021 |
Structural modifications on indole and pyrimidine rings of osimertinib lead to high selectivity towards L858R/T790M double mutant enzyme and potent antitumor activity.
EGFR inhibitors represent a significant milestone for treatment of non-small cell lung cancer, however, they suffer from the acquired drug resistance. Utilizing osimertinib as the lead compound, this work has explored the structural modifications on the indole and pyrimidine rings of osimertinib to generate novel osimertinib derivatives. The in vitro enzymatic and cellular studies showed that the derivatives possessed high selectivity towards double mutant EGFR and potent antitumor activity. Particularly, compound 6b-1, the most active compound, exhibited excellent inhibitory activity against double mutant EGFR (IC Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Cell Proliferation; Dose-Response Relationship, Drug; Drug Discovery; Drug Screening Assays, Antitumor; ErbB Receptors; Humans; Indoles; Molecular Docking Simulation; Molecular Structure; Mutation; Protein Kinase Inhibitors; Pyrimidines; Structure-Activity Relationship; Tumor Cells, Cultured | 2021 |
Design, synthesis and antitumor activity of novel thiophene-pyrimidine derivatives as EGFR inhibitors overcoming T790M and L858R/T790M mutations.
Five series of novel thiophene-pyrimidine derivatives (9a-h, 10a-f, 11a-f, 12a-f, 13a-f) have been synthesized and tested for their anti-proliferative activity against several cancer cell lines in which EGF is highly expressed. Most of the target compounds showed excellent activity against one or more cancer cell lines. The most promising compound 13a, of which IC Topics: Antineoplastic Agents; Cell Line, Tumor; Chemistry Techniques, Synthetic; Dose-Response Relationship, Drug; Drug Design; ErbB Receptors; Humans; Mutation; Protein Kinase Inhibitors; Pyrimidines; Structure-Activity Relationship; Thiophenes | 2020 |
Design, synthesis and biological evaluation of WZ4002 analogues as EGFR inhibitors.
A series of thirty two anilinopyrimidines derived from WZ4002 has been synthesized and evaluated for percentage inhibition of six different EGFR kinases using LanthaScreen binding assay method (EGFR d746 - 750) or Z'LYTE assay method (EGFR-WT, EGFR d746 - 750, EGFR T790M, EGFR T790M L858R, EGFR C797S and EGFR T790M L858R C797S). Ortho-hydroxyacetamide 10 exhibited complete inhibition of all the six kinases at 10µM. Against the triple mutant, EGFR T790M C797S L858R, compounds 9-12 exhibited complete inhibition at 10µM and nearly complete inhibition at 1µM. The target compounds were also evaluated using the MTT assay to determine their cytotoxic activity against human non-small cell lung cancer cells (PC9, PC9GR and H460) and mouse leukemic cells (Ba/F3 WT and Ba/F3T 3151). Overall, 7, 9-12, 30 and 31 were found to be the most potent compounds across all five cell lines. Topics: Acrylamides; Animals; Cell Line, Tumor; Cell Survival; Drug Design; Drug Screening Assays, Antitumor; ErbB Receptors; Humans; Mice; Mutagenesis, Site-Directed; Protein Kinase Inhibitors; Pyrimidines; Structure-Activity Relationship | 2017 |