Fundamentals of Medicinal Chemistry

its polarity and its relative solubilities in aqueous media and lipids. The stereo-

chemistry of the drug is particularly important, as stereoisomers often have

different biological effects, which range from inactive to highly toxic (see

Table 2.1).

Table 2.1 Variations in the biological activities of stereoisomers

First stereoisomer Second stereoisomer Example

Active Activity of same type

and potency

The R and S isomers of the antimalarial

chloroquine have equal potencies.

Cl N

NHCH(CH 3 )CH 2 CH 2 CH 2 N(C 2 H 5 ) 2

Active Activity the same type

but weaker

The E isomer of diethylstilbesterol, an estrogen

is only 7%as active as the Z isomer

HO

OH

C 2 H 5

C 2 H 5

Active Activity of a different

type

S-Ketamine is an anaesthetic

R-Ketamine has little anaesthetic action but is

a psychotic

Ketamine

Cl

O NHCH 3

Active No activity S-a-Methyldopa is a hypertensive drug but the

R isomer is inactive.

S- -Methyldopa NH

CH (^22)
CH 3
HO
HO
COOH
Active Active but different side
effects
Thalidomide: the S isomer is a sedative and has
teratogenic side effects. The R isomer is also a
sedative but has no teratogenic activity.
S-Thalidomide
NH
O
OO
N
H
O
54 AN INTRODUCTION TO DRUGS AND THEIR ACTION