New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety

Abstract

New 1′-homocarbanucleoside analogs with an optically active substituted bicyclo[2.2.1]heptane skeleton as sugar moiety were synthesized. The pyrimidine analogs with uracil, 5-fluorouracil, thymine and cytosine and key intermediate with 6-chloropurine (5) as nucleobases were synthesized by a selective Mitsunobu reaction on the primary hydroxymethyl group in the presence of 5-endo-hydroxyl group. Adenine and 6-substituted adenine homonucleosides were obtained by the substitution of the 6-chlorine atom of the key intermediate 5 with ammonia and selected amines, and 6-methoxy- and 6-ethoxy substituted purine homonucleosides by reaction with the corresponding alkoxides. No derivatives appeared active against entero, yellow fever, chikungunya, and adeno type 1viruses. Two compounds (6j and 6d) had lower IC50 (15 ± 2 and 21 ± 4 µM) and compound 6f had an identical value of IC50 (28 ± 4 µM) to that of acyclovir, suggesting that the bicyclo[2.2.1]heptane skeleton could be further studied to find a candidate for sugar moiety of the nucleosides.

A Molecular Docking of New 9β-Halogenated Prostaglandin Analogs with an Ester Group at C-6 Atom of the α-Side Chain

“…The docking score (PLANTPLP score) is a function described in Korb et al [20]. "For a strong binding, the score has a negative value; for weak or non-existing binding, the score has a less negative or even positive value" [21]. https://doi.org /10.37358/Rev.…”

1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Scaffold

“…Indeed, the primary alcohol reacted selectively to give the key nucleoside intermediate 5G isolated by simple crystallization in 71.3 % yield (Scheme 1). For comparison, 6chloropurine reacted with diol 2 in the same Mitsunobu reaction in 67.6 % yield [4,5].…”

Nitrogen-Based Heterocyclic Compounds: A Promising Class of Antiviral Agents against Chikungunya Virus

“…Therefore, D-6′-fluorinated-aristeromycin analogs (Figure 3) were designed to assess the inhibition of the human SAH and correlate the potential antiviral activity against CHIKV by a probable inhibition of nsP1. It was found that the 6-amino-purines (24,25,26) showed interesting results for SAH inhibition or for anti-CHIKV activity when compared with aristeromycin and also with other purines (27 and 28), pyrimidines (29)(30)(31)(32)(33), and phosphoramidates (34,35,36) as summarized in Table 2. These data confirmed the antiviral activity against CHIKV and also suggested that the observed activity may be due to an indirect effect on the activity of nsP1.…”

“…Moreover, this class of molecules is usually reported as being druggable and safe for human use, which makes it more attractive for further development. Therefore, in the present review, we will summarize natural and synthetic nitrogen-based heterocyclics and their derivatives with reported anti-CHIKV activity [ 9 , 11 , 19 , 25 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ] and explore the potential of these molecules as an interesting class for antiviral drug development.…”