Synthesis and Antiviral Activity of 1-[(1,5-Dialkyl-1H-1,2,4-triazol-3-yl)methyl]thymines

Abstract

Cycloaddition of the intermediates 2 with 1‐(cyanomethyl)‐thymine 3 furnished the 1,2,4‐triazolium salts 4, which rearranged spontaneously to the protonated salts 5. Hydrolysis of 5, in situ, afforded the title compounds 6. Compounds 6a‐c were screened against HIV‐1 (IIIB), HIV‐2 (ROD), and human cytomegalovirus (HMCV) and showed poor or no activity, respectively.

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

“…Compounds 8a-d were identified by the 1 H and 13 C NMR spectra, which are in agreement with those of the triazole analogues obtained previously [14][15][16][17][18][19][20][21][22][23][24][25]. The CH 2 signal appeared as a singlet at the Similarly, the 1,5-dialkyl-3-((thiophene-2yl)methyl)-1H-1,2,4-triazoles 10b-d were prepared by cycloaddition of the intermediates 4 with nitrile 9 in the presence of SbCl 5 in 77%, 85%, and 70% yields, respectively (Scheme 2).…”

“…Recently, the short-lived reactive intermediates 1-(chloroalkyl)-1-aza-2-azoniaallene salts (4) were used by Jochims and coworkers [13] in the syn- thesis of various 1,2,4-triazole compounds via cycloaddition with various unsaturated precursors in the presence of SbCl 5 . In our recent work, these cations have been utilized in the synthesis of new types of 1,2,4-triazoles such as C-nucleosides [14,15], acyclic C-nucleosides [16], pyrimidines [17], N-alkylphthalimides [18], D-mannopentitol-1yl-1,2,4-triazoles [19], 1H-indoles [20], quinolones [20], benzotriazoles [21], 3 -triazolo-thymidines [22], acetic acid alkylidene hydrazides [23], and 1,4-disubstituted piperazines [24,25]. The reactive intermediates (4) were obtained from the α,αdichloroazo compounds 3 [13] by treatment with SbCl 5 at −60 • C. At approximately −30 • C, the colour changed from orange to brown, indicating that cumulenes 4a-d underwent cycloaddition reactions with nitrile 5 to give inseparable 1,2,4-triazolium hexachloroantimonates 6a-d. After increase in the temperature above −30 • C, compounds 6a-d rearranged via [1,2]-migration [26,27] of the alkyl group at C-3 to N-5 accompanied by the elimination of CR 1 R 2 Cl group at N-1 leading to the protonated 1,5-dialkyl-3-((thiophene-3yl)methyl)-1H-1,2,4-triazolium salts 7a-d.…”

Synthesis and anti‐HIV Activity of Substituted 1,2,4‐Triazolo‐thiophene Derivatives.

“…Compounds 8a-d were identified by the 1 H and 13 C NMR spectra, which are in agreement with those of the triazole analogues obtained previously [14][15][16][17][18][19][20][21][22][23][24][25]. The CH 2 signal appeared as a singlet at the region δ H 3.93-4.17 ppm.…”

1,2,4-Triazoles: Synthetic approaches and pharmacological importance. (Review)

“…Extensive work has demonstrated the feasibility of using synthetic nucleoside and non-nucleoside analogues as anticancer and antiviral chemotherapeutic agents, and some of them are anti-HIV drugs, with 1-substituted pyrimidines being among the most widely studied [150]. Based on these biological data, the 1-[(1,5-dialkyl-1H-1,2,4-triazol-3-yl)methylthymines 116 [151] have been prepared from cycloaddition of the 1-cyanothymine 115 [152] with the reactive cumulenes 93, as potential anti-HIV agents since some acyclic 1,2,4-triazole C-nucleosides [153] showed remarkable antiviral properties against HSV-1 and -2 along with other viruses (Scheme 28). Tumor necrosis factor alpha (TNF-α) is an important cytokine secreted by activated monocytes/macrophages and possesses favorable biological activities, including direct tumor toxicities [154,155].…”