Fundamentals of Medicinal Chemistry

Table 7.1 Some of the classes of compound that are used as antifungal agents. Note the common structural

features.

Class General structure Examples

Azoles based

on 1,3- diazoles

N N

Ph

Cl

N NCH 2 OCH 2

H

Cl

Cl

Cl

N NCH

2

H

Cl

Cl

Cl

SCH 2

Clotrimazole Econazole Sulconazole

R

1

N

3

N

Azoles based

on 1,2,4-triazoles N

1

R

4

2

N

N

N NCH 2 CH 2 N

N

F

N

N

OH

F

N NCH

(^2) O
O
Cl Cl
CH 2 O N
N
CH 3
NCH
CH 3
Terconazole Fluconazole
Allylamines
R 3
R 2
N R 1
N
CH 3
CH 3
CH 3
CH 3 N CH 3
CH 3
SC
O
Naftifine Terbinafine Tolnaftate
N Ph
CH 3
Phenols
R
OH
CH 3
OH
CH 3
N
OH
Cl
I
CH 3
O N
CH 3
Ciclopirox
OH
HO
(CH 2 ) 5 CH 3
Hexylresorcinol Chloroxylenol Clioquinol

by bothfungistaticandfungicidalaction. Fungistatic action occurs when the

drug prevents the fungus reproducing with the result that it dies out naturally,

whilst fungicidal action kills the fungus. The suffixes-staticand -cideor -cidal

are widely used in other contexes to indicate these general types of action. Some

of the fungicides that act by disrupting the integrity of the cell membranes of

fungi are listed in Table 7.1.

7. 2. 1. 1 Azoles

Active azoles are usually derivatives of either 1,3-imidazoles or 1,2,4-imadazoles

that exhibit fungistatic activity at nanomolar concentration and fungicidal

activity at higher micromolar concentrations. Azoles are active against most

fungi that infect the skin and mucous membrane as well as some systemic fungal

infections, bacteria, protazoa and helminthi species. They are believed to mainly

EXAMPLES OF DRUGS THAT DISRUPT CELL MEMBRANES AND WALLS 133