Synthesis and Antiviral Activity of 1,5-and 1,3-Dialkyl-1,2,4-triazoleC-Nucleosides Derived from 1-(Chloroalkyl)-1-aza-2-azoniaallene Salts

Abstract

Reactions of alpha,alpha'-dichloroazo compounds 2 with SbCl5 gave 1-(chloroalkyl)-1-aza-2-azoniaallene salts 3 as reactive intermediates. Cycloadditions of 3 with the ribofuranosyl cyanide 4 afforded the beta-D-ribofuranosyl-1,2,4-triazolium salts 5, which rearranged spontaneously to salts 6. Hydrolysis of 6 gave the 1,2,4-triazole C-nucleosides 7, which yielded the free nucleosides 8 after deblocking. Analogously, 12 was prepared from the cycloaddition of 4 with the alpha-chloroazo compound 10 in the presence of SbCl5. Deblocking of 12 with sodium methoxide afforded 13. Compounds 8a,b,e,f and 13 were tested against HIV-1, HIV-2, HSV-1 and HSV-2 and were found to be inactive.

Synthesis of 3′‐1,2,4‐triazolo‐ and 3′‐1,3,4‐thiadiazoliminothymidines

“…Our work here is concerned with the synthesis of new 3 -azole analogues from the cycloaddition of 5 -acetyl-3 -deoxy-3 -isothiocyanatothymidine 9 and 3 -cyano-analogue 19, prepared from the antiviral nucleoside CNT [4,5], with some reactive cumulenes. In our recent work, these cumulenes have been used in the synthesis of new types of 1,2,4-triazole compounds such as C-ribonucleosides [15,16], acyclic C-nucleosides and homo-C-analogues [17], (D-manno-pentitol-1-yl)-anaslogues [18], as well as those 1,2,4-triazoles attached to thymine [19], phthalimide [20], indole [21], quinolone [21], and benzotriazole [22].…”

New benzylpiperazine derivatives bearing mono‐ and bis‐dialkyl substituted 1,2,4‐triazoles

“…Such examples of our recent work are 1,2,4-triazole C-nucleosides [28,29], acyclic C-nucleosides [30], pyrimidines [31], N-alkylphthalimides [32], Dmanno-pentitol-1-yl-1,2,4-triazoles [33], 1H-indoles as well as quinolines [34], benzotriazoles [35], 3 -triazolothymidines [36], N,N -trisubstituted 1,2,4-triazolo-piperazines [37], and 1,2,4-triazole derivatives of acetic acid alkylidene hydrazides [38]. In the present study, we prepared the 3-[4-(chloromethyl)-phenyl]-1,5-dimethyl-1H-1,2,4-triazole 6a and 6c, according to our reported method during the preparation of 6b and 6d [34], from the cycloaddition of 3 to 4-cyanobenzyl chloride 1.…”

“…These compounds were identified by homo-and heteronuclear NMR spectroscopic methods, HMBC [41], and mass spectra. EXPERIMENTAL [28][29][30][31][32][33][34][35][36][37] …”

Synthesis and anti‐HIV activity of substituted 1,2,4‐triazolo‐thiophene derivatives

“…• C. [1,2,4]triazolo [1,5-a] From 3b (1.20 g) [4][5]6,7, [1,2,4]triazolo [1,5-a]pyridine-2-yl)methyl)thiophene-2-yl)(4-nitro-phenyl)methanone (12). From 3c (1.17 g) and the nitrile 11 (1.36 …”

“…The 1,2,4-triazole moiety is present, for example, in certain antiasthmatic [1], antiviral (ribavirin) [2], antifungal (fluconazole) [3], antibacterial [4], and hypnotic [5] (triazolam) drugs. Owing to its broad spectrum of biological activity [6][7][8][9][10][11][12], the 1,2,4-triazole ring system represents an attractive target for the elaboration of solid-phase synthesis and the production of combinatorial libraries.…”