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MEDICINAL CHEMISTRY
Figure 1.11 Stereoisomers: a carbon atom bonded to four different substituents in a chiral carbon
or a stereogenic center. Such molecules cannot be superimposed upon their mirror image. A receptor will recognize one stereoisomer but not another. Such stereoisomers are designated as either
R or S. Stereoisomerism may also occur around double bonds, producing cis or trans orientations
of the substituents on either face of the double bond.
Even though enantiomeric drug pairs quite often show different potencies, they are
seldom antagonists of each other, since the differences in their action are due to differences in their binding properties; antagonists (see section 2.4) usually bind more
strongly than agonists, and the less active enantiomer of a pair is typically incapable of
displacing the more active one from the receptor.
Diastereomeric drugs—those having two or more asymmetric centers—are usually
active in only one configuration. Unlike enantiomers, which have identical physicochemical properties, the absorption, distribution, receptor binding, metabolism, and
every other aspect that influences the pharmacological activity of a drug are different
for each diastereomer.
1.4.2 Enantiomers and Pharmacological Activity
Lehman et al. (1986) stated the definitions of stereoselectivity in the following manner:
the better fitting enantiomer (the one with higher affinity for the receptor) is called the
eutomer, whereas the one with the lower affinity is called the distomer. The ratio of