Nucleic Acids in Chemistry and Biology

at the growing 3-end, this moiety cannot become phosphorylated by the next dNTP monomer. One of the
first compounds to be widely used was AZT (Figure 3.90) as it was found to be the least toxic of several
analogues in clinical use. A range of effective NRTIs is shown in Figure 3.90.
The active species for all nucleoside analogues of this type is the 2-deoxynucleoside 5-triphosphate. Since
the retrovirus does not encode its own kinase and because it is difficult to get highly anionic nucleotides into
cells, it is necessary for the native human cellular thymidine kinase to perform the initial phosphorylation

130 Chapter 3

Table 3.2 Anti-viral compounds in clinical use

Drug Virus

Amantadine, Rimantadine Influenza A
Oseltamivir, Zanamivir Influenza A and B
Zidovudine (AZT), Retrovir® HIV
Didanosine (ddI), Videx® HIV
Zalcitabine (ddC), Hivid® HIV
Stavudine (d4T), Zerit® HIV
Lamivudine (3TC), Epivir®, Zeffix® HIV and HBV
Abacavir, Ziagen® HIV
Emtricitabine, Emtriva® HIV and HBV
Tenofovir disoproxil (oral prodrug of PMPA) HIV and HBV
Nevirapine, Delavirdine, Efavirenz (non-nucleoside HIV
RT inhibitors NNRTIs)
Saquinavir, Ritonavir, Indinavir, Nelfinavir, Amprenavir, HIV protease inhibitors
Lopinavir, Atazanavir
Enfuvirtide HIV viral entry inhibitor
Adefovir dipivoxil (oral prodrug of PMEA) HIV and HBV
Acyclovir (ACV), Zovirax® Herpes Simplex Virus (HSV-1 and HSV-2) and
Varicella Zoster Virus (VZV)
Valaciclovir, Zelitrex®, Valtrex®oral prodrug of acyclovir) HSV-1, HSV-2 and VZV
Penciclovir, Denavir®, Vectavir® HSV-1, HSV-2 and VZV
Famciclovir, Famvir® HSV-1, HSV-2 and VZV
Idoxuridine, Herpid®, Idoxene®, etc. HSV-1, HSV-2 and VZV
Trifluridine (TFT), Viroptic® HSV-1, HSV-2 and VZV
Brivudin (BVDU), Zostex®, Zerpex®, etc. HSV-1 and VZV
Ganciclovir (DHPG), (GCV), Cymevene®, Cytovene® HSV-1 and HSV-2 cytomegalovirus (CMV)
Valganciclovir (VGCV), Valcyte® HSV-1, HSV-2 and CMV
Foscarnet, Foscavir® HSV-1, HSV-2, VZV, CMV and HIV
Cidofovir (HPMPC), (CDV), Vistide® Herpes viruses, papilloma-, polyoma-,
adeno- and poxviruses
Fomiversen, Vitravene® CMV retinitis
Ribavirin Influenza A and B, measles, respiratory
syncytial virus (RSV) and adenovirus

HO O

B

HO O N N

N

N

HN

NH 2

N O OH

N

H 2 N

O

S

X

HO O

Thy

N 3

HO O

Thy

X = H, lamivudine (3TC) (Epivir)

X = F, emtricitabine [(-)FTC]

abacavir (ABC)

(Ziagen)

B = Cyt; zalcitabine (ddC) (Hivid)

B = 6-oxopurine; didanosine (ddI) (Videx)

zidovudine (AZT)

(Retrovir)

stavudine (d4T)

(Zerit)

Figure 3.90 Structures of some licensed nucleoside-based reverse transcriptase inhibitors

http://www.ebook3000.com