Title:Synthesis of Thiazole, Thiophene, Pyran and Pyridine Derivatives Derived from 3-phenyl-1H-pyrazol-5(4H)-one with Anti-proliferative, Tyrosine Kinase and PIM-1 Kinase Inhibitions
Volume: 17
Issue: 4
Author(s): Rafat Milad Mohareb*Ibram Refat Mikhail
Affiliation:
- Department of Chemistry, Faculty of Science, Cairo University, Giza, A.R.,Egypt
Keywords:
Pyrazole derivatives, pyran, pyridine, antiproliferative activity, structure-activity relationship, tyrosine kinase inhibition.
Abstract:
Background: A wide range of pyrazole derivatives gained special attention due to their
wide range of pharmacological activities especially the therapeutic activities. Many pharmacological
drugs containing the pyrazole nucleus are known in the market.
Methods: The 3-phenyl-1H-pyrazol-5(4H)-one was the key starting compound for many heterocyclic
reactions to produce substituted and fused pyrazole derivatives.
Results: Antiproliferative activities of the produced compounds against six cancer cell lines A549,
HT-29, MKN-45, U87MG, and SMMC-7721 and H460 were measured through which compounds
showed high inhibitions. The most promising compounds were tested against tyrosine kinases (c-Kit,
Flt-3, VEGFR-2, EGFR, and PDGFR). Structure-Activity Relationship (SAR) was rationalized by
looking at the varying structural features of the molecules. In addition, the most active compounds
were selected for Pim-1 inhibition.
Conclusion: Thirty-nine pyrazole derivatives were synthesized. Nine of them 8b, 9, 12b, 12d, 14b,
15b, 18d, 18f, 19b, and 21d were the most active compounds toward the selected cancer cell lines.
Compounds 12b, 14b, 18d, 18f, and 21d showed high inhibitions toward the tyrosine kinases,
whereas compounds 14b, 18d, and 18f were the most potent inhibitors of Pim-1.