Synthesis of some new thienopyridine and pyridothienopyrimidine derivatives with expected antitumor activity

Abstract

The thioxopyridine derivative (2) on treatment with ethyl chloroacetate gave the corresponding ethyl 3-aminothieno [2,3-b]pyridin-2carboxylate (3). Condensation of 3 with Ac 2 O gave the corresponding 4-H-pyrido[3',2':4,5]thieno[3,2-d] [1,3]oxazine derivative (4). Reaction of 4 with bifunctional groups gave 3,4dihydropyrido[3',2':4,5]thieno[3,2-d]pyrimidines (5 a,b) and 2-carbamoyl-3-acetamidothieno[2,3-b]pyridine derivative (6). Intramolecular cyclization of 6 by Ac 2 O/AcOH gave (7). Reaction of 5b with different electrophilic reagents were studied. Also, 5a upon treatment with ethyl chloroacetate and/or methyl iodide (K 2 CO 3) furnished the corresponding Nethylacetate (13) and N-methyl derivative (16) respectively. Hydrazinolysis of 13 gave the corresponding acetohydrazide (14) which on treatment with benzaldehyde furnished the corresponding 1H-pyrazol-4-yl derivative (15). The IR, 1 H NMR and MS spectra of newly derivatives were discussed. The antitumor activity against the liver tumor cell line HepG 2 of the prepared compounds were tested. Compounds 8a, 14 were more potent (IC 50 = 2.75 and 2.12 g/ml) than the standard drug (IC 50 = 4.60 g/ml).

Synthesis and Biological Evaluation of New Pyridothienopyrimidine Derivatives as Antibacterial Agents and Escherichia coli Topoisomerase II Inhibitors

“…On the other hand, many reports have documented the important biological activities of thieno[2,3- b ]pyridine derivatives in anticancer [ 19 , 20 , 21 ], antimicrobial [ 22 , 23 ], antiviral [ 24 , 25 ], anti-inflammatory [ 26 ] and osteogenic [ 27 ] activities. As a result, thieno[2,3- b ]pyridine compounds and their fused derivatives with the bioactive pyrimidine ring [ 28 , 29 ] have attracted great interest in the last decade; several pyrido[3’,2’:4,5]thieno[3,2- d ]pyrimidine derivatives were synthesized and gave significant pharmacological properties as antimicrobial [ 30 , 31 , 32 ], anticancer [ 33 , 34 ] and protein kinase inhibitors [ 35 , 36 ]. Moreover, some thieno[2,3- b ]pyridine derivatives [ 37 ] and pyrimidine-based compounds [ 38 , 39 ] have been discovered in recent years as potent DNA gyrase and/or topoisomerase IV inhibitors, which encourage the design and synthesis of novel thienopyridine-fused pyrimidine compounds to obtain enhanced antibacterial activity ( Figure 1 ).…”