Organic Chemistry

Section 30.13 Economics of Drugs • Governmental Regulations 1225

30.12 Antiviral Drugs

Relatively few clinically useful drugs have been developed for viral infections. This

slow progress is due to the nature of viruses and the way they replicate. Viruses are

smaller than bacteria. A virus consists of nucleic acid—either DNA or RNA—

surrounded by a coat of protein. A virus penetrates a host cell or merely injects its nu-

cleic acid into the cell. In either case, the nucleic acid is transcribed and is integrated

into the host genome.

Most antiviral drugsare analogs of nucleosides, interfering with DNA or RNA

synthesis. In this way, they prevent the virus from replicating. For example, acyclovir,

the drug used against herpes viruses, has a three-dimensional shape similar to guanine.

Acyclovir can, therefore, fool the virus into incorporating it instead of guanine into the

virus’s DNA. Once this happens, the DNA strand can no longer grow, because

acyclovir lacks a group. The terminated DNA binds to DNA polymerase and

inactivates it irreversibly (Section 27.7).

Cytarabine, used for acute myelocytic leukemia, competes with cytosine for incor-

poration into viral DNA. Cytarabine contains an arabinose rather than a ribose

(Table 22.1). The group in the -position prevents the bases in DNA from

stacking properly (Section 27.7).

Ribarvirin is a broad-spectrum antiviral agent that inhibits viral mRNA synthesis

(Section 27.10). A step in the metabolic pathway responsible for the synthesis of

guanosine triphosphate (GTP) converts inosine monophosphate (IMP) into xanthosine

monophosphate (XMP). Ribarvirin is a competitive inhibitor of the enzyme that cat-

alyzes that step. Thus, ribarvirin interferes with the synthesis of GTP and, therefore,

with all nucleic acid synthesis.

Idoxuridine is approved in the United States only for the topical treatment of ocular

infections, although it is used for herpes infections in other countries. Idoxuridine has

an iodo group in place of the methyl group of thymine. The drug is incorporated into

DNA in place of thymine. Chain elongation can continue because idoxuridine has a

group. The DNA that has incorporated idoxuridine, however, is more easily

broken and is also not transcribed properly.

30.13 Economics of Drugs • Governmental Regulations

The average cost of launching a new drug is $100–$500 million. This cost has to be

amortized quickly by the manufacturer because the starting date of a patent is the date

the drug is first discovered. A patent is good for 20 years from the date it is applied for,

but because it takes an average of 12 years to market a drug after its initial discovery,

the patent protects the discoverer of the drug for an average of only 8 years. It is only

during the 8 years of patent protection that marketing the drug can provide enough

profit so that costs can be recovered and income can be generated to carry out research

3 ¿-OH

2 ¿-OH b

3 ¿-OH

HOCH 2 CH 2 OCH 2

O

idoxuridine

Herplex

approved for topical

ophthalmic use

N

I

HN

O

acyclovir

Aclovir

used against

herpes simplex infections

N N

HN N

O

H 2 N

ribavirin

Viramid

a broad-spectrum

antiviral agent

N

N

NH 2

HO HO HO

cytarabine

Cytosar

used against acute

myelocytic leukemia

N

N

NH 2

O

O

OH

HO

O

OH

O

HO OH

N

C

O

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