Design, Synthesis, and Antiviral Evaluation of Purine-β-lactam and Purine-aminopropanol Hybrids

Abstract

Purine-β-lactam chimera were prepared as a novel class of hybrid systems through N-alkylation of 6-benzylamino- or 6-benzyloxypurine with (ω-haloalkyl)-β-lactams, followed by reductive ring opening of the β-lactam ring by LiEt(3)BH to provide an entry into the class of purine-aminopropanol hybrids. Both new types of hybrid systems were assessed for their antiviral activity and cytotoxicity, resulting in the identification of eight purine-β-lactam hybrids and two purine-aminopropanol hybrids as promising lead structures.

Unpacking the Pathogen Box—An Open Source Tool for Fighting Neglected Tropical Disease

“…MMV688352 ( 638 ) was developed as part of a wider study, which sought to identify purine‐containing β‐lactam antivirals, where it showed encouraging activity against human respiratory syncytial virus, coxsackie B virus, and chikungunya virus, but was inactive against dengue . Chang et al.…”

Benzouracil–coumarin–arene conjugates as inhibiting agents for chikungunya virus

“…10 Arbidol was found to have an IC50 of 12.2 µM. In 2012, D'Hooghe et al 11 reported that two purine-β-lactam hybrids possess anti-CHIKV activity with EC50 of 17.11 and 13.01 µM, respectively, and selectivity 3 indices (SIs) of >5.75 and >4, respectively. Additionally, purine-aminopropanol exhibits an EC50 of 11.51 µM with an SI > 6.15.…”

The medicinal chemistry of Chikungunya virus

“…23) from Anacolosa pervilleana, namely Madagascan plant. Purine-based inhibitors D' Hooghe et al 100 reported the design and synthesis of a novel series of purine-b-lactam hybrids and purine-aminopropanol hybrids and their potential antiviral activities. 77,99 2.8.7.…”

“…77,99 2.8.7. 77,100 a All data are mean values ± standard deviation for at least three independent experiments. In total, nine different viruses were included in this study.…”