Synthesis and antitumor activity of some novel thiophene, pyrimidine, coumarin, pyrazole and pyridine derivatives
Date
2017
Authors
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
Croatian Pharmaceutical Society
Series Info
Acta Pharmaceutica
67
67
Scientific Journal Rankings
Abstract
2-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.
Description
Scopus
Keywords
October University for Modern Sciences and Arts, University for Modern Sciences and Arts, MSA University, جامعة أكتوبر للعلوم الحديثة والآداب, antitumor activity, coumarin, pyrazole, pyridine, pyrimidine, thiophene, 2 (1 amino 2 cyanoethylideneamino) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (1 amino 2 cyanoethylideneamino) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (2 cyano 3 phenylacrylamido) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (2 cyano 3 phenylacrylamido) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (2 cyanoacetamido) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (2 cyanoacetamido) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (3 (oxazol 2 yl carbamoyl) 5,6 dihydro 4h cyclopenta[b]thiophen 2 ylamino) 2 oxo n phenylacetohydrazonoyl cyanide, 2 (3 (thiazol 2 yl carbamoyl) 5,6 dihydro 4h cyclopenta[b]thiophen 2 ylamino) 2 oxo n phenylacetohydrazonoyl cyanide, 2 (4 (amino oxazol 2 yl) 6,7 dihydro 5h cyclopenta[4,5]thieno[2,3 d]pyrimidin 2 yl) acetonitrile, 2 (4 (aminothiazol 2 yl) 6,7 dihydro 5h cyclopenta[4,5]thieno[2,3 d]pyrimidin 2 yl) acetonitrile, 2 (4 amino 5 cyano 6 hydroxylpyridin 2 ylamino) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (4 oxo 3 (oxazol 2 yl) 3,4,6,7 tetrahydro 5h cyclopenta[4,5]thieno[2,3 d]pyrimidin 2 yl)acetonitrile, 2 (4 oxo 3 (thiazol 2 yl) 3,4,6,7 tetrahydro 5h cyclopenta[4,5]thieno[2,3 d]pyrimidin 2 yl)acetonitrile, 2 (4,6 diamino 5 cyanopyridin 2 ylamino) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (4,6 diamino 5 cyanopyridin 2 ylamino) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (5 amino 1h pyrazol 3 ylamino) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (5 amino 1h pyrazol 3 ylamino) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (6 amino 2 oxo 2,5 dihydropyrimidin 4 ylamino) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (6 amino 2 oxo 2,5 dihydropyrimidin 4 ylamino) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (6 amino 2 thioxo 2,5 dihydropyrimidin 4 ylamino) n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 (6 amino 2 thioxo 2,5 dihydropyrimidin 4 ylamino) n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 amino n (oxazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 amino n (thiazol 2 yl) 5,6 dihydro 4h cyclopenta[b]thiophene 3 carboxamide, 2 cyano n (oxazol 2 yl)acetamide, 2 cyano n (thiazol 2 yl)acetamide, antineoplastic agent, doxorubicin, n (3 (oxazol 2 yl carbamoyl) 5,6 dihydro 4h cyclopenta[b]thiophen 2 yl 2 oxo 2h chromene 3 carboxamide, n (3 (thiazol 2 yl carbamoyl) 5,6 dihydro 4h cyclopenta[b]thiophen 2 yl 2 oxo 2h chromene 3 carboxamide, unclassified drug, unindexed drug, antineoplastic agent, coumarin derivative, pyrazole derivative, pyridine derivative, pyrimidine derivative, thiophene derivative, antineoplastic activity, Article, carbon nuclear magnetic resonance, catalysis, cell growth, cell migration, cell proliferation, cell viability, controlled study, cyclization, drug synthesis, human, human cell, mass spectrometry, proton nuclear magnetic resonance, structure activity relation, synthesis, tumor cell line, Antineoplastic Agents, Cell Line, Tumor, Coumarins, Humans, Pyrazoles, Pyridines, Pyrimidines, Structure-Activity Relationship, Thiophenes