1. Case study of
stereochemistry
and drug design
PREPARED BY: ARZOO DHARASANDIYA GUIDED BY: UTTAM MORE
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
SHREE DHANVANTRY PHARMACY COLLEGE
2. Recemic switches
• A "racemic switch" is the redevelopment in single-enantiomer form of a drug that
was first approved as a racemate.
• Sometimes, the pharmaceutical activity is in only one enantiomer and the other
is inactive, or the "other" enantiomer has a different kind of activity from the first.
• Esmoprazole is the S-enantiomer of omeprazole.it is the most successful
racemic switches launched.
3. Racemic switches
Generelly the (±)-ibuprofen racemate is used ,but only (S)-
enantiomer has the anti-inflammatory action.
5. Difference between (+)prorpranolol and (-
)propranolol
• 1. The optical isomers of propranolol have been compared for their β-blocking
and antiarrhythmic activities.
• 2. the protein binding of propranolol to AGP is stereoselective for the S-
enantiomer, whereas binding to HSA favors (R)-propranolol.
• In whole plasma the binding to AGP is dominant so that the free fraction of the
R-enantiomer is greater than that of (S)-propranolol.
6. Stereoselective vascular effects of the (R)- and
(S)-enantiomers of propranolol and atenolol.
• The drugs are believed to be contraindicated when peripheral vascular disease
exists, presumably due to unopposed alpha-adrenergic vasoconstriction.
• However, little is known about direct vascular effects of beta-blockers or of
stereoselective effects on peripheral arteries.
• Therefore, we investigated the effects on forearm blood flow (FBF) of brachial
artery infusions of the (R)- and (S)- enantiomers of propranolol and their
inhibitory effects on isoprenaline (Iso)-induced vasodilatation by forearm venous
occlusion plethysmography in 12 healthy subjects.
• Only (R)-propranolol caused an increase in FBF (+21%, p < 0.05), whereas (S)-
propranolol had no direct effect on peripheral arteries.
• Our results indicate that the optically pure (R)- and (S)-enantiomers of
propranolol and atenolol do not exert direct vasoconstrictive effects.
8. • Thalidomide exists in two mirror-image forms: it is a racemic mixture of (R)- and
(S)-enantiomers.
• The (R)-enantiomer, shown in the figure, has sedative effects, whereas the (S)-
isomer is teratogenic.
• Under biological conditions, the isomers interconvert, so separating the isomers
before use is ineffective.
• he direct target of thalidomide had been a long-standing question. We identified
cereblon as a primary direct target protein for thalidomide teratogenicity using
new affinity bead technology in 2010.
9. • Thalidomide, sold under the brand name Immunoprin, among others, is
an immunomodulatory drug and the prototype of thethalidomide class of drugs.
Today, thalidomide is used mainly as a treatment of certain cancers (multiple
myeloma) and of a complication of leprosy.
12. naproxen
• (S)-(+)-naproxen is used to treat arthritis pain, but (R)-(–)-naproxen causes liver
poisoning with no analgesic effect.
• Mechanism of liver damage
• The mechanism of hepatotoxicity from naproxen is not known, but it is
metabolized by the cytochrome P450 system and idiosyncratic injury may be
due to a toxic metabolite. Cross sensitivity to hepatic injury with fenoprofen
suggests that the propionic acid may be responsible for the injury.
15. QUININE & quinidine
Quinine is a medication used to
treat malaria and babesiosis.
Quinidine is
a pharmaceutical agent that acts as
a class I antiarrhythmic agent (Ia) in
the heart.[1] It is
a stereoisomer of quinine
17. • When it comes to contraindications,
the amphetamine is noted to
increase cardiac output and blood
pressure.
• Thus, this drug is often prohibited
for use by people who are suffering
from heart diseases and
hypertension.
• There are some indications that
people who take the drugs together
with MAOI or monoamine oxidase
inhibitors can lead to life threatening
situations.
• On the other hand, the
dextroamphetamine is noted to have
contraindications of advanced
arteriosclerosis, symptomatic
cardiovascular diseases,
hypersensitivity and glaucoma.
• It is also noted that persons who
have taken MAOI drugs with the
dextroamphetamine can have
effects of hypertensive crises.
18.
19. • This drug is available as a mixture of both (S)-(–)-ketamine, also known
as esketamine, and (R)-(–)-ketamine, also known as arketamine.
• Pure esketamine is also available.
• The two have different dissociative and hallucinogenic properties, with
esketamine being more potent in isolation as a dissociative.
• The two enantiomers have inverse effects on the rate of glucose metabolism in
the frontal cortex.
21. OTHER EXAMPLES
CH3
HCCH2
CH3
CH3
H C CH2
H3C
S limonene (lemons) R limonene (oranges)
The more common R-
isomer possesses a
strong smell of
oranges.
The other mirror-image
isomer (or enantiomer), S-
limonene, has a pine or
turpentine-like odour.
22. O
CH3
H C CH2
H3C
O
CH3
HCH2C
CH3
S caravone
Caraway
seed
R caravan
spearment
Caraway Seed has a warm, pungent, slightly
bitter flavour with aniseed overtones.
Sweet spearmint, fresh herbalcaraway, fresh herbal
23. references
• i. Text book of organic chemistry – K.S. Mukherjee
• ii. Advanced Organic Chemistry – Jerry March
• iii. Organic Chemistry – Morrison and Boyd
• iv. STEREOCHEMISTRY BY FOYE
