Acyclovir: Chemical Structure, SAR, Mechanism of Action, Synthesis & Uses

Chemical Formula:

• C8H11N5O3

Structure of Acyclovir

SAR:

• Acyclovir is an antiviral medication primarily used for the treatment of herpes simplex virus infections.

• It is a guanosine analogue.

• The presence of an acyclic side chain attached to the guanine base is what allows the drug to be selectively phosphorylated by viral thymidine kinase, which is the key to its selective activity.

• Once this phosphorylation occurs, acyclovir acts as a chain terminator due to its lack of a 3' hydroxyl group for the attachment of further nucleotides.

Mechanism of Action:

• Acyclovir is a nucleoside analogue antiviral agent that primarily works against herpes simplex viruses (HSV-1, HSV-2) and varicella-zoster virus (VZV).

• Acyclovir is converted into its active form, acyclovir triphosphate, by viral and cellular thymidine kinases.

• The active form inhibits viral DNA polymerase by incorporating itself into the growing viral DNA strand, leading to chain termination and preventing viral replication.

Synthesis:

The synthesis of Acyclovir can be conducted in two steps:

• Reaction of guanine with 1,3-dibromopropane yields 9-(3-bromopropyl)guanine:

• Guanine + 1,3-Dibromopropane → 9-(3-Bromopropyl)guanine

• Subsequent reaction with hydroxylamine results in Acyclovir:

• 9-(3-Bromopropyl)guanine + NH2OH → Acyclovir + HBr

Uses:

Acyclovir is used to treat:

• Herpes simplex infections (oral and genital)

• Varicella-z