Professional Documents
Culture Documents
Jutti Levita
for Molecular Pharmacology and Medicinal Chemistry
References
Korolkovas, A., 1970, Essentials of Molecular
Pharmacology: Background for Drug Design,
Wiley-Interscience
STEREOCHEMISTRY 3
CONSIDERATIONS
The molecule with two tetrahedral centers is viewed along the C-C axis. The
atom in front is represented as a three-way branch, the atom in the back as a
circle with three outgoing bonds. This projection is most useful inconsideration of
steric relation between ligands linked to adjacent tetrahedral centers and is most
popular.
Sawhorse projection:
The C-C bond is viewed at an angle. The atom shown on the left of the
projection is also the one in the front. This projection is difficult to use with
acyclic molecules but is most popular for representation of cyclic molecules
e.g. saturated six-membered rings.
Haworth projection:
The difference in the pharmacological activity of many
stereoisomers is the best evidence for the existence of a
receptor due to 3 factors:
Conformer
Bacteriostatic activity of 9-
aminoacridine is directly related to a
minimal planar surface of about 38
2.
H3 C H3 C
S-Ibuprofen R-Ibuprofen
O O
NHCH3 NHCH3
Cl Cl
S-(+)-Ketamine R-(-)-Ketamine
2-4 times more potent than Causes spontaneous motor
R-(-)-ketamine in activity and post-emergent
anaesthesia distress
Influence of Stereochemistry
on Pharmacological Activity
Phentolamine
OH
H H
Adrenaline HO N
CH3
HO
Salbutamol H
OH
H
(Ventolin) HOCH2 N CH3
C
(Anti-asthmatic) CH3
(selective -Blocker) HO CH3
CH3
Propranolol H
(non selective -Blocker) O N CH3
H
OH
-Adrenoceptor
H-Bonding
region Ionic
H-Bonding
region bonding
Van der Waals region
bonding region
H-Bonding
region
-Adrenoceptor
H-Bonding
region
Ionic
H-Bonding bonding
region region
a-Adrenoceptor
HO N
CH3
HO
ADRENALINE
OH
H H
-Adrenoceptor
HO N
CH3
HO
ADRENALINE
OH
H H
HOCH2 N CH3
-Adrenoceptor C
CH3
CH3
HO
SALBUTAMOL
OH
H H
a-Adrenoceptor
HOCH2 N CH3
C
CH3
CH3
HO
SALBUTAMOL
OH
H H
HOCH2 N CH3
a-Adrenoceptor
C
CH3
CH3
HO
SALBUTAMOL
Optical Isomerisms in Drugs