372 Chemotherapy

NH2 HN

N N N

N O H2N N N
HO HO
O

S
Lamivudine Abacavir

Classification According to the Treatment Protocol

According to the treatment protocol antiviral agents are classified as follows:
I. Treatment of respiratory virus infection
Adamantane derivatives: Amantadine, Rimantadine
II. Treatment of herpes and cytomegalo viruses infection.
a. Purine nucleotides: Acyclovir, Ganciclovir, Vidarabine.
b. Pyrimidine nucleosides: Trifluouridine, Idoxuridine.
c. Phosphorus derivatives: Foscarnet sodium.
III. Treatment of HIV infections
a. RT inhibition.
1. Purine derivatives: Didanosine.
2. Pyrimidine derivative: Zidovudine, Stavudine.
3. Non-nucleosides: Nevirapine, Delaviridine, Efavirenz.
b. Protease inhibition: Saquinavir, Indinavir, Ritonavir, Nelfinavir, Amprenavir, Lopinavir.
c. Integration inhibition: Zintevir.

SYNTHESIS AND DRUG PROFILE

I. Nucleotide analogues
a. Purine nucleosides and nucleotides
i. Acyclovir (Ocuvir, Zovirax, Cyclovir)
O

N
HN

H2N N
N
CH2OCH2CH2OH

2-Amino-9-((2-hydroxyethoxy)methyl)-1H-purin-6(9H)-one
 Antiviral Agents 373

Synthesis
O O
(i) [(CH3)3Si]2N2
N N
HN (C2H5)3N HN

(ii) C6H5COOCH2CH2OCH2Cl
H2N N H 2N N N
N 2-(chloromethoxy)
H ethyl benzoate CH2OCH2CH2OCOC6H5
2-Amino-1H-purin-6(9H)-one –HCl

NaOH
–C6H5COONa

N
HN

H2N N N

CH2OCH2CH2OH
Acyclovir

Metabolism: The bioavailability of acyclovir is 15%–30 % and it is metabolized to 9-carboxy-methoxyme-

thyl guanine, which is inactive.
Properties and uses: Acyclovir is a white crystalline powder, slightly soluble in water, soluble in dimethyl
sulphoxide and in dilute mineral acids and alkali hydroxides, and very slightly soluble in ethanol. It is a
purine nucleoside analogue, used as antiviral agent against herpes viruses.

Assay: Dissolve the sample in anhydrous acetic acid and titrate with 0.1 M perchloric acid. Determine the
end point potentiometrically. Perform a blank titration.
Dose: For herpes virus infections the administered dose for immuno-suppressed patients is up to 10 mg/kg
body weight every 8 h.
Dosage forms: Acyclovir cream B.P., Acyclovir eye ointment B.P., Acyclovir intravenous infusion B.P.,
Acyclovir oral suspension B.P., Acyclovir tablets B.P., Dispersible acyclovir tablets B.P.

Metabolism of Valacyclovir: The related analogue 6-deoxy acyclovir is a prodrug form of acyclovir that is
activated through metabolism by xanthine oxidase.
Metabolism of Cidofovir: It is metabolized by phosphorylation and it gives cidofovir diphosphate.

Metabolism of Famciclovir: It is a prodrug of penciclovir, which is formed in vivo by hydrolysis of acetyl

groups and oxidation at the 6th position by the mixed function oxidase. Penciclovir and its metabolite pen-
ciclovir triphosphate posseses antiviral activity.