February 13, 2018

Nicholas Schmidt

Medicinal Chemistry 2 (CHM 352)

Homework Assignment 2 – Antiviral Medications

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Acyclovir (Zovirax) is the most commonly prescribed antiviral medication for herpes

simplex virus (HSV) infections, such as genital herpes, shingles, chicken pox, and encephalitis

caused by HSV. Acyclovir’s mechanism of action is to target the viral thymidine kinase, so it can

be phosphorylated to mimic the nucleotide guanine in infected cells. When incorporated into

viral DNA, synthesis is unable to continue as acyclovir cannot accept another nucleotide,

meaning acyclovir is a chain terminator. Acyclovir is synthesized by 9-(2-

propionyloxyethoxymethyl)guanine, like many purine derivatives. Acyclovir is available as a

tablet, powder for solution, capsule, ointment, suspension, or injection, or mixture. Many

companies manufacture acyclovir, such as Mylan Pharmaceuticals Inc., Dava Pharmaceuticals

Inc., Glaxosmithkline, and others. Side effects with acyclovir are minimal, with nausea and

diarrhea being most common, but cessation of acyclovir treatment have been associated with

nephrotoxicity and neurotoxicity.

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Oseltamivir (Tamiflu) is the most commonly prescribed antiviral medication to treat

influenza Type A and Type B infections (also known as the flu) in patients older than one year

old. Its mechanism of action is to inhibit viral neuraminidase, thereby stopping the maturation of

viral proteins and preventing the replication of the virus. According the a patent on carbocylic

compounds, oseltamivir and other neuraminidase inhibitors are synthesized from a compound

identified as STR74 or STR75. Oseltamavir is formulated as an oral capsule or a power for

suspension. The only manufacturer of oseltamivir is Hoffmann la Roche Inc. Osmeltamivir’s

adverse effects include nausea and vomiting, but more serious effects such as liver inflammation,

seizure, and abnormal heart rhythms have been reported.

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Sofosbuvir (Sovaldi) is the one of the most commonly prescribed antiviral medications to

treat chronic Hepatitis C, caused by the Hepatitis C Virus (HCV). Sofosbuvir acts by inhibiting

the non-structural protein 5B (HCV NS5B) as a chain terminator, preventing HCV viral

replication. Synthesis of sofosbuvir is done with β-d-2′-Deoxy-2′-α-fluoro-2′-β-C-methyl

nucleosides, which are modified into various HCV NS5B inhibitors, including

sofosbuvir. Sofosbuvir is available as a tablet, either with or without film coating. Sofosbuvir is

currently manufactured exclusively by Gilead. Sofosbuvir has minimal side effects, the most

common being headache and fatigue.

References

Schaeffer, H. J. Patent US4294831 - Purine derivatives

https://www.google.com/patents/US4294831?dq=4294831&hl=en&sa=X&ved=0ahUKE

wjG9eqGjZzZAhWRqlMKHZPYByUQ6AEIKTAA (accessed Feb 10, 2018).

Sofosbuvir https://www.drugbank.ca/drugs/DB08934 (accessed Feb 10, 2018).

Oseltamivir https://www.drugbank.ca/drugs/DB00198 (accessed Feb 10, 2018).

Bischofberger, N. W.; Kim, C. U.; Lew, W.; Liu, H.; Williams, M. A. Patent US5763483 -

Carbocyclic compounds

https://www.google.com/patents/US5763483?dq=5763483&hl=en&sa=X&ved=0ahUKE

wiM6u_EkZzZAhUBn1MKHZtmC48Q6AEIKTAA (accessed Feb 10, 2018).

Aciclovir https://www.drugbank.ca/drugs/DB00787 (accessed Feb 10, 2018).