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).