Fundamentals of Medicinal Chemistry

CONH 2

N

CH 3

CONH 2

H

H 2 N

CH 3

NN

NH

N

NH

O

NH CH

3

HO

CH 3

HO CH 3

O

O

O

NH

O

NH N

S

N

S

COR

O

O

OH

HO

HO

OH OCONH^2

OH

OH

Bleomycin A 2

R = −NHCH 2 CH 2 CH 2 S(CH 2 ) 2

+

Figure 7.15 The bleomycins. The drug bleomycin sulphate is a mixture of a number of

bleomycins

occuring glycoproteins that exhibit antitumour activity. Their action is not

understood, but the nucleic acid fragments produced cannot be rejoined by

DNA ligases. Unfortunately, they exhibit a number of unwanted side effects.

However, other classes of drug are in the development stage.

7.6 Antiviral drugs

It has been found that viruses (Appendix 10) utilize a number of virus specific

enzymes during replication. These enzymes and the processes they control are

significantly different from those of the host cell to make a useful target for

medicinal chemists. Consequently, antiviral drugs usually act by either inhibit-

ing viral nucleic acid synthesis, inhibit attachment to and penetration of the host

cell or inhibit viral protein synthesis.

7.6.1 Nucleic acid synthesis inhibitors

These drugs usually act by inhibiting the polymerases or reverse transcriptases

required for nucleic acid synthesis. They are usually analogues of the purine and

pyrimidine bases found in the nucleic acids (Figure 7.16). Their general mode of

action often involves conversion to the corresponding triphosphate by the host

ANTIVIRAL DRUGS 155