Pyrimidine-5-carbonitriles – part III: synthesis and antimicrobial activity of novel 6-(2-substituted propyl)-2,4-disubstituted pyrimidine-5-carbonitriles

Abstract

The reaction of 6-(2-methylpropyl or 2-phenylpropyl)-2-thiouracil-5-carbonitriles (4a,b) with various arylmethyl halides, 2-bromoethyl methyl ether, benzyl chloromethyl ether, and 2-bromomethyl-5-nitrofuran in N,N-dimethylformamide or acetone yielded the corresponding substituted thio-3,4-dihydro-4-oxopyrimidine-5-carbonitrile analogues 5a–h, 6a,b, 7, and 8a,b, respectively. Treatment of 5c with phosphorus oxychloride and N,N-dimethylaniline yielded the 4-chloropyrimidine derivative 9, which was allowed to react with various arylthiols, arylamines, and 1-substituted piperazines to yield the respective 4-arylthio 10a–d, 4-arylamino 11a–d, and 4-piperazino 12a,b derivatives. The newly synthesized compounds were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 5e, 5f, 5g,h, 7, 8a,b, and 12a display marked antibacterial activity, particularly against the Gram-positive bacteria. None of these compounds are active against C. albicans.

Crystal structure of 2-[(4-fluorobenzyl)sulfanyl]-4-(2-methylpropyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile, C16H16FN3OS

“…A large number of pyrimidine-based antimetabolites are currently used as potent and selective anticancer activity [10][11][12]. In addition, marked antibacterial and antifungal activities were observed for several pyrimidine-5-carbonitrile derivatives [13][14][15][16][17]. Here, we report the crystal structure of the recently synthesized [16] title compound (C 16 H 16 FN 3 OS).…”

Crystal structure of 6-oxo-4-propyl-2-(propylthio)-1,6-dihydropyrimidine-5-carbonitrile, C11H15N3OS

“…Large array of pyrimidine-based analogues have emerged as useful therapies against human immunode ciency viruses (HIV) [5][6][7][8], hepatitis B viruses (HBV) [9], herpes simplex viruses (HSV) [10,11], in uenza viruses [12] and varicella-zoster virus (VZV) [13]. Moreover, several pyrimidine derivatives were reported to display antibacterial [14][15][16][17] and antifungal [18] activities. Taking into consideration the diverse chemotherapeutic properties of pyrimidine-5-carbonitrile derivatives, we report herein the synthesis and the crystal structure of the title compound.…”

Crystal structure of 5-ethyl-6-[(3-methylphenyl)sulfanyl]pyrimidine-2,4(1H,3H)-dione, C13H14N2O2S

“…In addition, numerous pyrimidine-related derivatives displayed marked activities against herpes simplex viruses (HSV) [8], and hepatitis B viruses (HBV) [9]. Moreover, potent anticancer [10,11] and antimicrobial activities [12][13][14][15] were observed among several pyrimidine-2,4-dione derivatives. In the present investigation, we report the crystal structure of the title compound, which was proved to exhibit marked anti-HIV-1 activity [7].…”