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Medicinal Chemistry Research

, Volume 27, Issue 2, pp 618–633 | Cite as

The uses of cyclohexan-1,4-dione for the synthesis of thiophene derivatives as new anti-proliferative, prostate anticancer, c-Met and tyrosine kinase inhibitors

  • Rafat M. Mohareb
  • Fatima Al-Omran
  • Rehab A. Ibrahim
Original Research

Abstract

A series of heterocyclic compounds derived from the dihydrobenzo[b]thiophene derivatives were synthesized all the synthesized compounds were determined by elemental analysis, 1H NMR, 13C NMR, and MS. The newly synthesized compounds were evaluated for their in-vitro cytotoxic activity against c-Met kinase, and the six typical cancer cell lines (A549, H460, HT-29, MKN-45, U87MG, and SMMC-7721). All target compounds were initially tested for their anti-proliferative activity against human prostatic cancer PC-3 cell line. The most promising compounds were 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 7b, 7c, 11c, 11d, and 11f were further investigated against tyrosin kinase (c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR). Compounds 5e, 5f, 5h, 11d, and 11f were selected to examine their Pim-1 kinase inhibition activity where compounds 5e, 5h, and 11f showed high activities.

Keywords

Thiophene Thiazole Pyrazole Anti-proliferative Tyrosine kinases 

Notes

Acknowledgements

R. M. Mohareb would like to thank the Alexander von Humboldt Foundation in Bonn, Germany for affording him regular fellowship for doing research and completing this work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Rafat M. Mohareb
    • 1
  • Fatima Al-Omran
    • 2
  • Rehab A. Ibrahim
    • 3
  1. 1.Chemistry DepartmentFaculty of Science Cairo UniversityNew CairoEgypt
  2. 2.Department of ChemistryFaculty of Science, Kuwait UniversitySafatKuwait
  3. 3.Institute of Engineering and TechnologyNew CairoEgypt

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