Study Set Content:
1R,2S - Ephedrine
If the priority sequence proceeds to the right, or in a clockwise direction, the chiral center is designated with an
R-absolute configuration
when the priority sequence proceeds to the left, or in a counterclockwise direction
S
d-designation using the Fisher system. With the CIP system, norepinephrine is assigned the
R-absolute configuration.
In many instances, two molecules can have different absolute configurations as designated by the CIP system, but the same relative orientation of the functional groups relevant for biologic activity
In many instances, two molecules can have different absolute configurations as designated by the CIP system, but the same relative orientation of the functional groups relevant for biologic activity
Both R-norepinephrine and S-propranolol, however, shows that the hydroxyl group, basic amine, and aromatic rings of both compounds occupy the same regions in
3D space
The more potent enantiomer must be involved in a minimum of three intermolecular interactions with the surface of the biologic target and that the less potent enantiomer only interacts with two sites.
The Easson-Stedman Hypothesis
can achieve the same interactions with the receptor as S- (+)epinephrine
N-methyldopamine
N-methyldopamine can achieve the same interactions with the receptor as S- (+)epinephrine; therefore, it is not surprising that its vasopressor response is the same as that of S-(+)-epinephrine and less than that o
R-(−)- epinephrine.
are molecules that are nonsuperimposable, non–mirror images. This type of isomer can result from the presence of more than one chiral center in the molecule, double bonds, or ring systems.
Diastereomers
Examples of chiral drugs with 2 or more asymmetric centers
Isomethadol
Morphine
Chloramphenicol
Labetalol
Enlapril
Restricted bond rotation caused by carbon–carbon double bonds (alkenes or olefins) and similar systems, such as imines (C=N), can produce
stereoisomers
ouble bonds (alkenes or olefins) and similar systems, such as imines (C=N), can produce stereoisomers. These are also referred to as
geometric isomers,
Restricted bond rotation caused by carbon–carbon double bonds (alkenes or olefins) and similar systems, such as imines (C=N), can produce stereoisomers. These are also referred to as geometric isomers, although they more properly are classified as
diastereomers
from the German zusammen, meaning “together”
cis- or Z-isomer
when they are on opposite sides, the designation is
trans- or E-
(from the German entgegen, meaning
opposite
Takes place via rotation about one or more single bonds. Such bond rotation results in non-identical spatial arrangement of atoms in a molecule.
Conformational isomerism
An (blank) in the length of an alkyl chain (homologation), branching, and alteration of ring size can have a profound effect on the potency and pharmacologic activity of the molecule.
increase or decrease
A change in the length of an alkyl chain by one CH2 unit or branch alters the (blank) of the molecule and, therefore, its properties of absorption, distribution, and excretion.
lipophilic character
