An Efficient Access to Pyrimidine‐based Polyfunctional Heterocycles with Anticipated Antibacterial Activity

Abstract

6‐Amino‐2‐thioxotetrahydropyrimidine‐5‐carbonitrile derivative 2 was synthesized in a good yield via refluxing a mixture of arylidene 1 and thiourea in a highly basic sodium ethoxide solution. Subsequently, the synthesized pyrimidine‐2‐thione derivative 2 was allowed to interact with diversified nucleophiles and electrophiles under various reaction conditions in order to have a feasible access to further new and assorted fused heterocycles. Finally, the biological activity of the newly synthesized fused pyrimidines was screened in vitro against four different Gram‐positive and Gram‐negative bacterial strains. All the developed heterocycles were adequately characterized utilizing 1H‐NMR, 13C‐NMR, Fourier transform infrared, elemental analysis, and electrospray ionization–mass spectrum and tested for their antibacterial activity.

Pyrazolo[3,4‐d]pyrimidine‐based scaffolds as antibacterial agents: Synthetic strategies, reactions, and in vitro biological evaluation

“…Encouraged by the above‐mentioned facts and as a part of our ongoing endeavors to develop valuable heterocyclic building blocks, [ 22, 23 ] feasible and straightforward synthetic routes were utilized to assemble novel fused and attached pyrazolo[3,4‐ d ]pyrimidine derivatives, aiming to promote their synthetic potential and investigate the associated biological activities.…”

“…[20] Noteworthy, pyrazolo [3,4-d]pyrimidines emerged as vital pharmaceutically relevant molecules in view of their presence as part of several approved marketed drugs such as parsaclisib, ibrutinib (Imbruvica), allopurinol (Zyloric), umbralisib (Ukoniq). [21] 2 | RESULTS AND DISCUSSION Encouraged by the above-mentioned facts and as a part of our ongoing endeavors to develop valuable heterocyclic building blocks, [22,23] feasible and straightforward synthetic routes were utilized to assemble novel fused and attached pyrazolo [3,4-d]pyrimidine derivatives, aiming to promote their synthetic potential and investigate the associated biological activities.…”

A review on pyrimidine‐based derivatives: Synthesis and their biological application

“…These interactions are essential for the proper functioning of nucleic acids, the transmission of genetic information, and a wide range of other cellular processes (Figure 3) [46]. Additionally, pyrimidine derivatives have a wide range of biological properties in the therapeutic industry, including antimicrobial [47], antibacterial [48], antifungal [49], anti-inflammatory [50], antitumor [8], anticancer [51], antioxidant [52], antihypertension [53], anti-HIV [54], antimalarial [55], antiviral [56], insecticide [57], antiplasmodial [58] activities.…”

Recent Development of Pyrimidine‐Containing Antimicrobial Agents

“…As fused pyrimidine heterocycles possess many pharmacological and therapeutic merits, hydrogenation derivatization of pyrimidine ring is also a strategy to explore new antibacterial agents. Thus, Mourad et al [47] designed and synthesized a series of 6-amino-2-thioxotetrahydropyrimidine-5-carbonitrile derivatives and evaluated their antibacterial activity. In this series, compound 80 ( Figure 13) was found to exhibit potent antibacterial activity against four tested strains of B. subtilis, Staphylococcus enteritis, P. aeruginosa and E. coli with activity indexes of 100-116.6 % (norfloxacin: 100 %).…”

“…As fused pyrimidine heterocycles possess many pharmacological and therapeutic merits, hydrogenation derivatization of pyrimidine ring is also a strategy to explore new antibacterial agents. Thus, Mourad et al . designed and synthesized a series of 6‐amino‐2‐thioxotetrahydropyrimidine‐5‐carbonitrile derivatives and evaluated their antibacterial activity.…”