Abstract
Background: Among the wide range of heterocycles, tetrahydrobenzothienopyridine derivatives acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs containing the thiophene nucleus were known in the market.
Method: A series of tetrahydrobenzothienopyridine derivatives were synthesized from the reaction of 2-amino- 3-benzoyl-4,5-dihydrobenzo[b]thiophen-6(7H)-one, synthesized and used for further heterocyclization reactions through reaction with different reagents.
Results: Antiproliferative evaluations and c-Met kinase, Pim-1 kinase inhibitions were performed where some compounds revealed high activities.
Conclusion: The inhibition of the newly synthesized compounds towards c-Met kinase, the five c-Metdependent cancer cell lines (A549, HT-29, MKN-45, U87MG, and SMMC-7721) and one c-Met-independent cancer cell line (H460) were investigated using foretinib as a standard drug. The results showed that compounds 6b, 7e, 9b, 9e, 16c and 20d were more active than foretinib. Furthermore, compounds 6b, 13b, 16b and 16c were selected to examine their Pim-1 kinase inhibition activity, where compounds 16b and 16c were of high potencies with IC50 values of 0.28 and 0.32 µM, while compounds 6b and 13b were less effective (IC50 > 10 µM).
Keywords: Thienopyridine, pyran, pyridine, thiophene, thiazole, kinase inhibitor.
Anti-Cancer Agents in Medicinal Chemistry
Title:New Approaches for the Uses of Cyclohexan-1,4-dione for the Synthesis of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-b]pyridine Derivatives used as Potential Anti-prostate Cancer Agents and Pim-1 Kinase Inhibitors
Volume: 18 Issue: 12
Author(s): Rafat M. Mohareb*, Nadia Y. Megally Abdo and Karam A. EL-Sharkawy
Affiliation:
- Department of Chemistry, Faculty of Science, Cairo University, Giza,Egypt
Keywords: Thienopyridine, pyran, pyridine, thiophene, thiazole, kinase inhibitor.
Abstract: Background: Among the wide range of heterocycles, tetrahydrobenzothienopyridine derivatives acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs containing the thiophene nucleus were known in the market.
Method: A series of tetrahydrobenzothienopyridine derivatives were synthesized from the reaction of 2-amino- 3-benzoyl-4,5-dihydrobenzo[b]thiophen-6(7H)-one, synthesized and used for further heterocyclization reactions through reaction with different reagents.
Results: Antiproliferative evaluations and c-Met kinase, Pim-1 kinase inhibitions were performed where some compounds revealed high activities.
Conclusion: The inhibition of the newly synthesized compounds towards c-Met kinase, the five c-Metdependent cancer cell lines (A549, HT-29, MKN-45, U87MG, and SMMC-7721) and one c-Met-independent cancer cell line (H460) were investigated using foretinib as a standard drug. The results showed that compounds 6b, 7e, 9b, 9e, 16c and 20d were more active than foretinib. Furthermore, compounds 6b, 13b, 16b and 16c were selected to examine their Pim-1 kinase inhibition activity, where compounds 16b and 16c were of high potencies with IC50 values of 0.28 and 0.32 µM, while compounds 6b and 13b were less effective (IC50 > 10 µM).
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Mohareb M. Rafat *, Abdo Y. Megally Nadia and EL-Sharkawy A. Karam , New Approaches for the Uses of Cyclohexan-1,4-dione for the Synthesis of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-b]pyridine Derivatives used as Potential Anti-prostate Cancer Agents and Pim-1 Kinase Inhibitors, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (12) . https://dx.doi.org/10.2174/1871520618666180604091358
DOI https://dx.doi.org/10.2174/1871520618666180604091358 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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