Mohareb R.M.Abdo N.Y.M.El-Sharkawy K.A.Department of ChemistryFaculty of ScienceCairo UniversityGizaEgypt; Chemistry DepartmentFaculty of EducationAlexandria UniversityAlexandria21526Egypt; Department of Pharmaceutical ChemistryCollege of PharmacyJazan UniversityP.O. Box 114Jazan45142Saudi Arabia; Department of ChemistryFaculty of BiotechnologyOctober University for Modern Sciences and Arts (MSA)El-Wahat Road6th October CityCairoEgypt2020-01-092020-01-09201818715206https://doi.org/10.2174/1871520618666180604091358PubMedID29866019https://t.ly/2dX8kScopusBackground: 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 ?M, while compounds 6b and 13b were less effective (IC50 > 10 ?M). � 2018 Bentham Science Publishers.EnglishKinase inhibitorPyranPyridineThiazoleThienopyridineThiophene2 amino 3 benzoyl 4 5 dihydrobenzo[b]thiophen 6(7h) one2 amino 7 oxo 4 phenyl 5 6 7 8 tetrahydrobenzo[4 5]thieno[2 3b]pyridine 3 carbonitrile2 amino 7 oxo 4 phenyl 8 (2 phenylhydrazono) 5 6 7 8 tetrahydrobenzo[4 5]thieno[2 3 b]pyridine 3 carbonitrile2 amino 7 oxo 4 phenyl 8 2 amino 8 (2 (4 chlorophenyl)hydrazono) 7 oxo 4 phenyl 5 67 8 tetrahydrobenzo [4 5]thieno[2 3 b]pyridine 3 carbonitrile2 amino 8 (2 (4 methoxyphenyl)hydrazono) 7 oxo 4 phenyl 5 6 7 8 tetrahydrobenzo [4 5]thieno[2 3 b]pyridine 3 carbonitrile2 hydroxy 7 oxo 4 phenyl 5 6 7 8 tetrahydrobenzo[4 5]thieno[2 3 b]pyridine 3 carbonitrile2 hydroxy 7 oxo 4 phenyl 8 (2 phenylhydrazono) 5 6 7 8 tetrahydrobenzo[4 5]thieno[2 3 b]pyridine 3 carbonitrile2 hydroxy 8 (2 (4 methoxyphenyl)hydrazono) 7 oxo 4 phenyl 5 6 7 8 tetrahydrobenzo[4 5]thieno[2 3 b]pyridine 3 carbonitrile3 9 diamino 1 (4 bromophenyl) 7 phenyl 1 4 5 6 tetrahydropyrido[3 2 :4 5]thieno[2 3 f]quinoline 2 8 dicarbonitrile3 9 diamino 1 (4 bromophenyl) 7 phenyl 5 6 dihydro 1hchromeno[6 5 :4 5]thieno[2 3 b]pyridine 2 8 dicarbonitrile3 9 diamino 1 (4 chlorophenyl) 7 phenyl 1 4 5 6 tetrahydropyrido[3 2 :4 5]thieno[2 3 f]quinoline 2 8 dicarbonitrile3 9 diamino 1 (4 chlorophenyl) 7 phenyl 5 6 dihydro 1hchromeno[6 5 :4 5]thieno[2 3 b]pyridine 2 8 dicarbonitrile3 9 diamino 1 7 diphenyl 1 4 5 6 tetrahydropyrido[3 2 :4 5]thieno[2 3 f]quinoline 2 8 dicarbonitrile3 amino 1 (4 bromophenyl) 9 hydroxy 7 phenyl 5 6 dihydro 1hchromeno[6 5 :4 5] thieno[2 3 b]pyridine 2 8 dicarbonitrile3 amino 1 (4 chlorophenyl) 9 hydroxy 7 phenyl 5 6 dihydro 1hchromeno[6 5 :4 5] thieno[2 3 b]pyridine 2 8 dicarbonitrile3 amino 9 hydroxy 1 7 diphenyl 1 4 5 6 tetrahydropyrido[2 :4 5]thieno[2 3 f]quinoline 2 8 dicarbonitrile3 amino 9 hydroxy 1 7 diphenyl 5 6 dihydro 1h chromeno[6 5 :4 5]thieno[2 3 b]pyridine 2 8 dicarbonitrile5 6 7 8 tetrahydrobenzo[4 5]thieno[2 3 b]pyridine5 6 dihydro 1h chromeno[6 5 :4 5]thieno[2 3 b]pyridine8 (2 (4 chlorophenyl)hydrazono) 2 hydroxy 7 oxo 4 phenyl 5 6 7 8 tetrahydrobenzo [4 5]thieno[2 3 b]pyridine 3 carbonitrile8 (2 2 hydroxy 8 (2 (4 methoxyphenyl)hydrazono) 7 oxo 4 phenyl 5 6 7 8 tetrahydrobenzo[4 5]thieno[2 3 b]pyridine 3 carbonitrileandrogen receptorantineoplastic agentcclohexane 1 4 dioneprotein kinase Pim 1protein tyrosine kinasescatter factor receptortetrahydrobenzothienopyridinethienopyridine derivativeunclassified drugunindexed drugantineoplastic agentcyclohexanone derivativeprotein kinase inhibitorprotein kinase Pim 1pyridine derivativeantineoplastic activityantiproliferative activityArticlecancer cell linecell growthcell proliferationcolon cancercontrolled studydrug synthesiselemental analysisenzyme activityenzyme substrateGI50humanhuman cellIC50infrared spectroscopylung cancerMTT assaynon small cell lung cancerprostate cancerprotein expressionradiosensitivitystomach cancerantagonists and inhibitorschemical structurechemistrydose responsedrug effectdrug screeningmetabolismstructure activity relationsynthesistumor cell lineAntineoplastic AgentsCell Line, TumorCell ProliferationCyclohexanonesDose-Response Relationship, DrugDrug Screening Assays, AntitumorHumansMolecular StructureProtein Kinase InhibitorsProto-Oncogene Proteins c-pim-1PyridinesStructure-Activity RelationshipArticlehttps://doi.org/10.2174/1871520618666180604091358PubMedID29866019