Download - Stereochemistry in Pharmacy and Drug Therapy
Stereochemistry Importance of Chirality in Pharmacy
R/S notation E/Z notation
Enantiomers
(S)-(+)-Lactic acid (R)-(-)-Lactic acid
DiastereomersD-Threose D-Erythreose
Racemate/ Racemic mixture Enantiopure/ Enantiomerically pure
Racemate vs Enantiopure
In a survey of 1850 drugs: 1327 were synthetically obtained 528 contained one or more chiral centers 88.4% were used as a racemate
Racemate
Enantiomers in Biological Systems
Thalidomide
Thalidomide became an over the counter drug in Germany on October 1, 1957.
Shortly after the drug was sold, in Germany, between 5,000 and 7,000 infants were born with phocomelia (malformation of the limbs).
Throughout the world, about 10,000 cases were reported of infants with phocomelia due to thalidomide; only 50% of the 10,000 survived.
Contergan
Today, thalidomide is being marketed by Celgene mainly as a treatment of certain cancers and of a complication of leprosy.
Contergan
To separate unwanted effects if they reside exclusively in one enantiomer
Less drug dosage Easier assessment of
drugs
Enantiopure
Escitalopram
Complexity of process Cost Thermodynamically unstable causing
racemization to occur◦ e.g. Thalidomide undergoes racemization in
aqueous media
Disadvantages
Enantiomerically pure drugs are genarally preferred over racemates
Disadvantage lies at the cost and the technology needed to separate the enantiomers
Conclusion