Uses of dimedone to synthesis pyrazole, isoxazole and thiophene derivatives with antiproliferative, tyrosine kinase and Pim-1 kinase inhibitions
| Autor: | Fatma M. Manhi, Amal Abdelwahab, Rafat M. Mohareb, Mahmoud Ali Abdelaziz Mahmoud |
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| Rok vydání: | 2020 |
| Předmět: |
biology
010405 organic chemistry Stereochemistry Kinase Organic Chemistry Pyrazole 01 natural sciences 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry.chemical_compound chemistry Dimedone biology.protein Thiophene Bioorganic chemistry General Pharmacology Toxicology and Pharmaceutics Isoxazole Tyrosine kinase Platelet-derived growth factor receptor |
| Zdroj: | Medicinal Chemistry Research. 29:1536-1551 |
| ISSN: | 1554-8120 1054-2523 |
| DOI: | 10.1007/s00044-020-02579-4 |
| Popis: | We are aiming in this work to synthesize target molecules not only possess antitumor activities but also kinase inhibitors. The target molecules were obtained from dimedone, which reacted with triethoxymethane to produce a product that is capable for many heterocyclization reactions to give fused pyrazole, thiophene and isoxazole derivatives. Compounds 7b, 7c, 7d, 9b, 11, 12c, 12d, 14b, 16b, 17c, 17d, 18c, 18d, and 18e were the most cytotoxic compounds, their further tests toward the five tyrosine kinases c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR and Pim-1 kinase showed that compounds 7b, 7d, 11, 12c, 14b, 16b, 17d, 18d, and 18e were the most potent of the tested compounds toward the five tyrosine kinases and compounds 7b, 7d, 14b, 16b, and 18e were of the highest inhibitions toward Pim-1 kinase. PAINS the most cytotoxic compounds showed zero PAINS alert, therefore, these compounds can be used as useful drugs in the future. |
| Databáze: | OpenAIRE |
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