Synthesis, Antimicrobial, and Anti-inflammatory Activities of Novel 5-(1-Adamantyl)-4-arylideneamino-3-mercapto-1,2,4-triazoles and Related Derivatives

Abstract

The reaction of 5-(1-adamantyl)-4-amino-3-mercapto-1,2,4-triazole (5) with various aromatic aldehydes in ethanol or acetic acid yielded the corresponding 4-arylideneamino derivatives 6a–v. Treatment of the 4-(2,6-difluoro- and dichlorobenzylideneamino) derivatives 6o and 6q with 1-substituted piperazines, and formaldehyde solution in ethanol afforded good yields of the corresponding 5-(1-adamantyl)-4-(2,6-dihalobenzylideneamino-2-(4-substituted-1-piperazinylmethyl)-1,2,4-triazoline-3-thiones 7a–p. 5-(1-Adamantyl)-4-arylideneamino-2-(4-ethoxycarbonyl-1-piperidylmethyl)-1,2,4-triazoline-3-thiones 8a–n, were similarly prepared via the reaction of the corresponding arylideneamino derivative with ethyl 4-piperidinecarboxylate and formaldehyde solution in ethanol. Compounds 6a–v, 7a–p and 8a–n were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Several derivatives showed good or moderate activities, particularly against the tested Gram-positive bacteria. In addition, the in vivo anti-inflammatory activity of 21 compounds was determined using the carrageenan-induced paw oedema method in rats. Compounds 7d, 7g, 7i, 7j, 7l, 8c, 8e and 8l showed good or moderate dose-dependent activity in this area.

Ethyl 2-(3-methyl-5-sulfanylidene-4,5-dihydro-1H-1,2,4-triazol-4-yl)acetate

“…For background information on the title compound, see: Saadeh et al (2010); Akhtar et al (2008); Al-Omar et al (2010). For the biological activity of 1,2,4-triazoline-thiones, see: Pitucha et al (2010).…”

Synthesis and Crystallographic Insight into the Structural Aspects of Some Novel Adamantane-Based Ester Derivatives

“…To date, seven adamantane derivatives have been applied in clinical usage to treat acne vulgaris [1], Alzheimer's disease [2], as an anti-viral [3][4][5][6][7] and for type-2 diabetes [8][9][10], while the others are in development as potential therapeutics for iron overload disease, neurological conditions, malaria, tuberculosis and cancers [11]. Previous studies on adamantyl-based compounds revealed their antioxidant and anti-inflammatory properties [12][13][14]. As a reactive oxygen species, hydrogen peroxide is generated as a by-product of biological reaction.…”

Crystal structure of 3-(adamantan-1-yl)-1-[(4-benzylpiperazin-1-yl)methyl]-4-[(E)-(2,6-difluorobenzylidene)amino]-1H-1,2,4-triazole-5(4H)-thione, C31H36F2N6S

“…1,2,4-Triazole derivatives were also recognized as a structural motif of particular value in medicinal chemistry possessing diverse biological activities [21][22][23]. In the present study, we report the crystal structure together with the synthesis of the title 1,2,4-triazole-N-Mannich base which was reported to exhibit marked antifungal activity [17]. This contribution is part of study on admantyl-based drugs [24] There is one complete molecule in the asymmetric unit of the title structure.…”

“…Several adamantane-based drugs are currently used as e cient therapies for the control central nervous disorders [9][10][11][12]. In addition, potent antimicrobial [13][14][15][16][17][18], anti-in ammatory [16][17][18] and anticancer [19,20] activities were reported for adamantane-based derivatives. 1,2,4-Triazole derivatives were also recognized as a structural motif of particular value in medicinal chemistry possessing diverse biological activities [21][22][23].…”