New Acyclic Quinoxaline Nucleosides. Synthesis and Anti-Hiv Activity

Abstract

A series of acyclonucleosides substituted 1-(4,5-dihydroxypentyl) (13-8) and 2-(4,5-dihydroxypentyloxy)quinoxalines (19-24) were synthesized by the sharpless asymmetric dihydroxylation of the derivatives 1-6 and 7-12, respectively. Treatment of the quinoxaline base 26 with (R)-2,2-dimethyl-1,3-dioxolan-4-ylmethyl-p-toluenesulfonate (27) in the presence of NaH/DMF furnished 28. Acid hydrolysis of 28 gave 1-(2,3-dihydroxypropyl)-6,7-dimethyl-quinoxaline-2-one (29). Alternatively, 29 was prepared by sharpless dihydroxylation of 30. All the compounds were evaluated for their in vitro anti-HIV-1 and HIV-2 in MT-4 cell and found inactive, except 29, which showed inhibition of HIV-1 with EC50 value of 0.15 +/- 0.1 microg/ml and a therapeutic index (SI) of 73.

A Comprehensive In Silico Perspective For Discovery of Novel Inhibitory Candidates Targeting Versatile Transcriptional Repressor MBD2

“…Here, we have realized that numerous hit compounds (see Supplementary Table S1) and also unlisted ones consists of remarkable groups such as pyridine, quinoxaline, imidazole, isoquinoline, which are incorporated either in nucleosides and nucleotide analogs, or at least related structures to directly nucleotides or DNA-related constructs [44][45][46] . For instance, quinoxaline and isoquinoline derivatives have been demonstrated to bind and act as antagonists of cyclic nucleotide-related enzymes such as cyclic nucleotide phosphodiesterase 47 and P2X7 nucleotide receptor 48,49 , suggesting these groups might be attractive for DNA-or nucleotide-recognizing domains.…”

A Comprehensive In Silico Perspective For Discovery of Novel Inhibitory Candidates Targeting Versatile Transcriptional Repressor MBD2

“…Certain ligands have been listed in Supplementary Table S1 as hitter ligands by ltering according to resulted binding a nity and physicochemical properties such as complexity, molecular weight, tPSA, and also convenience to be purchasable or synthesizable for de facto attempts. Here, we have realized that numerous hit compounds (see Supplementary Table S1) and also unlisted ones consist of remarkable groups such as pyridine, quinoxaline, imidazole, isoquinoline, which are incorporated either in nucleosides and nucleotide analogs, or at least related structures to directly nucleotides or DNA-related constructs (Ali et al, 2008;García et al, 2008;Röthlisberger et al, 2017). For instance, quinoxaline and isoquinoline derivatives have been demonstrated to bind and act as antagonists of cyclic nucleotide-related enzymes such as cyclic nucleotide phosphodiesterase (Parra et al, 2001) and P2X7 nucleotide receptor (Humphreys et al, 1998;Watano et al, 2002), suggesting these groups might be attractive for DNA-or nucleotide-recognizing domains.…”

Novel Synthetic Routes to Prepare Biologically Active Quinoxalines and Their Derivatives: A Synthetic Review for the Last Two Decades

“…Quinoxalines have various pharmacological applications such as anti-inflammatory, antidepressant-tranquillizing, antitumor, and anti-hepatitis B virus (HBV) activity. The biological significance of quinoxaline derivatives prompted Ali et al [54] to synthesize some homo unsaturated acylnucleosides quinoxaline derivatives.…”