Structural and Synthetic Aspects of Small Ring Oxa- and Aza-Heterocyclic Ring Systems as Antiviral Activities

Abstract

Antiviral properties of different oxa- and aza-heterocycles are identified and properly correlated with their structural features and discussed in this review article. The primary objective is to explore the activity of such ring systems as antiviral agents, as well as their synthetic routes and biological significance. Eventually, the structure-activity relationship (SAR) of the heterocyclic compounds, along with their salient characteristics are exhibited to build a suitable platform for medicinal chemists and biotechnologists. The synergistic conclusions are extremely important for the introduction of a newer tool for the future drug discovery program.

Keywords: Structure Activity Relationship (SAR); antiviral agents; heterocycles; natural products; synthetic methods.

Figure 1

Global mortality rate per year due to different viral infections [13].

Figure 2

First FDA-approved antiviral drug Idoxuridine.

Figure 3

Representative examples of antiviral drug candidates.

Figure 3

Representative examples of antiviral drug candidates.

Figure 4

Representative nucleoside drugs.

Figure 4

Representative nucleoside drugs.

Figure 5

Representative natural products having antiviral activities.

Figure 6

Chemical structure of darunavir (1).

Figure 7

The interaction of darunavir with HIV-1 PR.

Scheme 1

Synthesis of darunavir.

Figure 8

Fluoroquinolone-isatin-thiosemicarbazone hybrid (2), a potential anti-HIV agent.

Scheme 2

Synthesis of fluoroquinolone-isatin-thiosemicarbazone hybrid.

Figure 9

Chemical structure of amprenavir (3).

Figure 10

H-bonds and water-mediated interactions formed by amprenavir with the active site.

Scheme 3

Synthesis of amprenavir.

Figure 11

Chemical structure of asunaprevir (4).

Figure 12

Structure of HCV NS3/4A protease in complex with asunaprevir.

Scheme 4

Synthesis of anti-HCV agent asunaprevir.

Figure 13

3-(1,2,4-oxadiazole)-quinolone derivative (5) with anti-HCV activities.

Scheme 5

Synthesis of 3-(1,2,4-oxadiazole)-quinolone derivatives.

Figure 14

Chemical structure of grazoprevir (7).

Scheme 6

Synthesis of grazoprevir.

Figure 15

Chemical structure of lamivudine (6).

Scheme 7

Synthesis of anti-HBV agent lamivudine.

Figure 16

Chemical structure of entecavir (28).

Figure 17

Entecavir triphosphate docking with HBVpol.

Scheme 8

Synthesis of entecavir.

Scheme 9

Synthesis of dehydro-andrographolide (35) and andrographolide (36) derivatives.

Figure 18

Chemical structure of ribavirin (10).

Scheme 10

Synthesis of ribavirin.

Figure 19

Chemical structure of iso-Valganciclovir hydrochloride (21).

Scheme 11

Synthesis of iso-valganciclovir hydrochloride.

Figure 20

Chemical structure of ganciclovir (22).

Scheme 12

Synthesis of Ganciclovir.

Figure 21

1,2,4-triazol-quinoxalin derivative (19), a new anti-human-cytomegalovirus (HCMV) agent.

Scheme 13

Synthesis of 1,2,4-triazol-quinoxalin derivative.

Figure 22

Anti Ebola agent remdesivir (15).

Scheme 14

Synthesis of remdesivir.