Synthesis and Antifungal Activity of Pyrimidine Derivatives Containing an Amide Moiety

Abstract

In this study, 17 novel pyrimidine derivatives containing an amide moiety were synthesized. Then their in vitro antifungal activities against Botryosphaeria dothidea (B. dothidea), Phomopsis sp., and Botrytis cinereal (B. cinereal) were determined. A preliminary biological test showed that compounds 5-bromo-2-fluoro-N-(2-((2-methyl-6-(trifluoromethyl)pyrimidin-4-yl)oxy)phenyl)benzamide (5f) and 5-bromo-2-fluoro-N-(3-((2-methyl-6-(trifluoromethyl)pyrimidin-4-yl)oxy)phenyl)benzamide (5o) exhibited higher antifungal activity against Phomopsis sp., with an inhibition rate of 100% compared to that of Pyrimethanil at 85.1%. In particular, compound 5o exhibited excellent antifungal activity against Phompsis sp., with the EC50 value of 10.5 μg/ml, which was even better than that of Pyrimethanil (32.1 μg/ml). As far as we know, this is the first report on the antifungal activities against B. dothidea, Phomopsis sp., and B. cinereal of this series of pyrimidine derivatives containing an amide moiety.

An overview on synthesis and biological activity of pyrimidines

“…93) exhibited excellent antifungal activity against Phompsis sp. with the EC50 value of 10.5 µg /ml, which were even better than that of Pyrimethanil [41].…”

“…Compound 5-bromo-2-fluoro-N-(3-((2-methyl-6-(trifluoromethyl)pyrimidin-4-yl)oxy)phenyl)benzamide (93) exhibited excellent antifungal activity against Phompsis sp. with the EC50 value of 10.5 µg /ml, which were even better than that of Pyrimethanil[41].…”

“…Scheme 11 Synthesis of 2-Thioxo-1,2,3,4-tetrahydropyrimidine derivatives (41) Othman et al; reported the reaction of 2-methoxyaniline (42) with chloroacetonitrile in ethanol leading to the formation of the key intermediate 2-((2-methoxyphenyl)amino) acetonitrile (43), which was treated with different aromatic aldehydes namely; benzaldehyde and/or 4-methylbenzaldehyde in glacial acetic acid to produce the corresponding acrylonitrile derivatives (44), which were subsequently reacted with urea and/or thiourea in refluxing ethanol containing a catalytic amount of HCl to afford the pyrimidine derivatives (45) [18].…”

Design, Synthesis, and Bioactivities of Novel Trifluoromethyl Pyrimidine Derivatives Bearing an Amide Moiety

“…Based on the aforementioned considerations and our previous works (Wu et al, 2019;Wu et al, 2020;Wu et al, 2021;Yu et al, 2021), the amide is linked to the trifluoromethyl pyrimidine backbone through an oxygen ether. Finally, we designed and synthesized a novel series of trifluoromethyl pyrimidine derivatives containing an amide moiety due to the molecularly active splicing strategy (Figure 1).…”

Synthesis, antimicrobial activity, and molecular docking studies of new fused pyrimidinethiones

“…Polyfunctional reagent cyanothioacetamide (1) is broadly utilized in synthetic organic chemistry [1][2][3] as sulfur and nitrogen heterocyclic compounds, which often have biological activities [4]. Pyrimidines have received attention in medicinal chemistry due to their wide-spread pharmacological properties including antimicrobial [5], antithrombotic [6], antiplatelet [7], antitrypanosom [8], antiproliferative [9], anticancer [10], antifungal [11], antidepressant [12], antiparasitic [12], and herbicidal activity [13]. Inspired from the above observation and in continuation our previous work [14][15][16][17][18][19][20][21][22], we decided to explore the possibility of synthesizing new fused pyrimidines via the reaction of compounds 3 [23] and 4 with some nucleophile reagents.…”