Efficient synthesis and molecular docking of novel antibacterial pyrimidines and their related fused heterocyclic derivatives

Abstract

3-(Benzo[d] [1,3]dioxol-5-yl)-1-(thiophen-2-yl)prop-2-en-1-one reacted with each of thiourea and 6-amino-2-thioxo-2,3-dihydropyrimidin-4(1H)-one to give the corresponding pyrimidine-2(1H)-thiones. Then, these compounds reacted with the appropriate hydrazonyl chlorides in dioxane in the presence of triethylamine to afford the corresponding [1,2,4]triazolo[4,3-a]pyrimidines and their related fused pyridines. Moreover, chalcone was cyclocondensed with 2-cyanothioacetamide to give pyridine-2(1H)-thione and taken as a key synthon to novel 2-(methylthio)pyridothienopyrimidin-4(3H)-one derivative. The above derivative reacted with the appropriate hydrazonyl chlorides in dioxane in the presence of triethylamine to yield the corresponding pyridothieno[3,2-d][1,2,4]triazolo[4,3-a]pyrimidines. Study of the in vitro antimicrobial activities of the newly pyrimidines were performed. Pyridothienopyrimidine 24a showed the highest inhibitory activity against all bacteria with MIC values of 3.9, 7.81, 7.81, and 15.62 μg/mL, respectively, against Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Streptococcus mutans, respectively, as compared to reference drugs. Molecular docking was studied to predict of the optimized conformation of pyrimidines as active ligands against the Escherichia coli alkaline phosphatase. The structures of the hybrid molecules were elucidated by IR, Mass, 1 H NMR, and 13 C NMR spectra as well as elemental analyses.

Synthesis and biological activity of 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide derivatives

“…IR (KBr) in cm −1 : 1630 (νС=О), 3280 (νN-H), 1520 (δN-H); 1572-1591 (С=С, С=N), 2960 (νC-H), 1443 (δC=C 6 -CH 3 ), 1167, 1050 (C-O-C). 1 General procedure for the synthesis of compound [3][4][5][6][7][8][9][10][11][12] Appropriate ketone was added to a solution of compound 2 in 5 ml of ethanol (Figure 1). The reaction mixture was boiled for 1 h. The solid obtained by concentration was collected and purified by recrystallization.…”

“…Over the last decade there has been considerable interest in the synthesis and pharmacological study of pyrimidine derivatives [3][4][5][6][7]. The pyrimidine fragment has been gaining special interest as it is part of many biological active compounds: vitamins, nucleotides and nucleosides.…”

Novel Nicotinonitriles and Thieno[2,3‐b]pyridines as Potent Biofilm and COX‐2 Inhibitors: Synthesis, In Vitro and In Silico Studies

“…The most common synthetic route to pyridine-2(1H)-thiones includes the cyclocondensation of the appropriate chalcones with 2-cyanothioacetamide. Thus, the reaction of chalcones 3 a-3 c [49,50] with 2-cyanothioacetamide 4, in boiling ethanol at reflux in the presence of piperidine as an organocatalyst, afforded 6-(4-chlorophenyl)-4-(thiophen-2-yl)-2-thioxo-1,2-dihydropyridine-3-carbonitrile 5 a, 4-(benzo[d] [1,3]dioxol-5yl)-6-(thiophen-2-yl)-2-thioxo-1,2-dihydropyridine-3-carbonitrile 5 b [49] and 4-(3,5-dibromo-4-ethoxyphenyl)-2-thioxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile 5 c, respectively (see Scheme 1 and Experimental section).…”

Discovery of novel 3‐{[(5,5‐dimethyl‐4,5‐dihydroisoxazol‐3‐yl)sulfonyl]methyl}benzo[d]isoxazole analogs as promising very long chain fatty acids inhibitors

“…More than 90% of the world' pesticide patents are about heterocyclic compounds [32–34] . Benzo‐heterocyclic compounds are an important branch of heterocyclic compounds, and they occupy an important position in the research and development of pesticides and medicines [35,36] . There are many benzo five‐membered heterocyclic herbicides on the market, all of which have good herbicidal activity, such as fenoxaprop‐p‐ethyl and metamifop [37–39] .…”

“…[32][33][34] Benzo-heterocyclic compounds are an important branch of heterocyclic compounds, and they occupy an important position in the research and development of pesticides and medicines. [35,36] There are many benzo five-membered heterocyclic herbicides on the market, all of which have good herbicidal activity, such as fenoxaprop-p-ethyl and metamifop. [37][38][39] Benfuresate and ethofumesate are both benzofuran ring herbicides that can control annual or perennial grass weeds.…”