Albratty M.El-Sharkawy K.A.Alam S.Department of Pharmaceutical ChemistryCollege of Pharmacy Jazan UniversityP.O. Box 114Jazan45142Saudi Arabia; Department of Organic ChemistryFaculty of BiotechnologyOctober University for Modern Sciences and Arts (MSA)El-Wahat Road 6October CityEgypt2020-01-092020-01-09201713300075https://doi.org/10.1515/acph-2017-0004PubMedID28231053https://t.ly/W5xwPScopus2-Cyano-N-(thiazol-2-yl) acetamide (2a) and 2-cyano-N-(oxazol- 2-yl) acetamide (2b) were obtained via the reaction of ethyl cyanoacetate with either 2-aminothiazole (1a) or 2-aminooxazole (1b). The formed products were directed toward the reaction with cyclopentanone and elemental sulfur in the presence of triethylamine to give cyclopenta[b]thiophene derivatives (3a,b). The latter products were reacted with either ethyl cyanoacetate or malononitrile to form compounds 4a,b and 5a,b, respectively. Compounds 4a,b were aimed at synthesizing some heterocyclic compounds; thus internal cyclization reactions were introduced to form compounds 6a,b. Also, compounds 4a,b reacted with salicylaldehyde, hydrazine derivatives and either urea or thiourea to produce coumarin derivatives (7a,b), pyrazole derivatives (8a-d) and pyrimidine derivatives (9a-d), respectively. Reaction of either benzaldehyde or benzene diazonium chloride (11) with compounds 4a,b afforded compounds 10a,b and 12a,b, respectively. On the other hand, compounds 5a,b underwent internal cyclization to form pyrimidine derivatives 13a,b. Also, when compounds 5a,b reacted with either ethyl cyanoacetate or malononitrile, they gave pyridine derivatives (15a-d) through the formation of intermediates (14a-d). Finally, formation of fused pyrimidine derivatives (17a,b) was achieved through the reaction of compounds 5a,b and salicylaldehyde applying two different pathways. The first pathway used a catalytic amount of piperidine to form compounds 16a,b; the latter products underwent cyclization to give compounds 17a,b. The second pathway, using a catalytic amount of sodium ethoxide solution directly in one step, afforded compounds 17a,b. Structures of the newly synthesized compounds were established using IR, 1H NMR, 13C NMR and mass spectrometry and their antitumor activity was investigated. Some of these compounds showed promising inhibitory effects on three different cell lines. However, fused pyrimidine acetonitrile derivatives 6a and 6b exerted the highest inhibitory effect, comparable to that of doxorubicin. � by Karam Ahmed El-Sharkawy 2017.EnglishOctober University for Modern Sciences and ArtsUniversity for Modern Sciences and ArtsMSA Universityجامعة أكتوبر للعلوم الحديثة والآدابantitumor activitycoumarinpyrazolepyridinepyrimidinethiophene2 (1 amino 2 cyanoethylideneamino) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (1 amino 2 cyanoethylideneamino) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (2 cyano 3 phenylacrylamido) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (2 cyano 3 phenylacrylamido) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (2 cyanoacetamido) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (2 cyanoacetamido) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (3 (oxazol 2 yl carbamoyl) 5,6 dihydro 4h cyclopenta[b]thiophen 2 ylamino) 2 oxo n phenylacetohydrazonoyl cyanide2 (3 (thiazol 2 yl carbamoyl) 5,6 dihydro 4h cyclopenta[b]thiophen 2 ylamino) 2 oxo n phenylacetohydrazonoyl cyanide2 (4 (amino oxazol 2 yl) 6,7 dihydro 5h cyclopenta[4,5]thieno[2,3 d]pyrimidin 2 yl) acetonitrile2 (4 (aminothiazol 2 yl) 6,7 dihydro 5h cyclopenta[4,5]thieno[2,3 d]pyrimidin 2 yl) acetonitrile2 (4 amino 5 cyano 6 hydroxylpyridin 2 ylamino) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (4 oxo 3 (oxazol 2 yl) 3,4,6,7 tetrahydro 5h cyclopenta[4,5]thieno[2,3 d]pyrimidin 2 yl)acetonitrile2 (4 oxo 3 (thiazol 2 yl) 3,4,6,7 tetrahydro 5h cyclopenta[4,5]thieno[2,3 d]pyrimidin 2 yl)acetonitrile2 (4,6 diamino 5 cyanopyridin 2 ylamino) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (4,6 diamino 5 cyanopyridin 2 ylamino) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (5 amino 1h pyrazol 3 ylamino) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (5 amino 1h pyrazol 3 ylamino) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (6 amino 2 oxo 2,5 dihydropyrimidin 4 ylamino) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (6 amino 2 oxo 2,5 dihydropyrimidin 4 ylamino) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (6 amino 2 thioxo 2,5 dihydropyrimidin 4 ylamino) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 (6 amino 2 thioxo 2,5 dihydropyrimidin 4 ylamino) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 amino n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 amino n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide2 cyano n (oxazol 2 yl)acetamide2 cyano n (thiazol 2 yl)acetamideantineoplastic agentdoxorubicinn (3 (oxazol 2 yl carbamoyl) 5,6 dihydro 4h cyclopenta[b]thiophen 2 yl 2 oxo 2h chromene 3 carboxamiden (3 (thiazol 2 yl carbamoyl) 5,6 dihydro 4h cyclopenta[b]thiophen 2 yl 2 oxo 2h chromene 3 carboxamideunclassified drugunindexed drugantineoplastic agentcoumarin derivativepyrazole derivativepyridine derivativepyrimidine derivativethiophene derivativeantineoplastic activityArticlecarbon nuclear magnetic resonancecatalysiscell growthcell migrationcell proliferationcell viabilitycontrolled studycyclizationdrug synthesishumanhuman cellmass spectrometryproton nuclear magnetic resonancestructure activity relationsynthesistumor cell lineAntineoplastic AgentsCell Line, TumorCoumarinsHumansPyrazolesPyridinesPyrimidinesStructure-Activity RelationshipThiophenesArticlehttps://doi.org/10.1515/acph-2017-0004PubMedID28231053