Drug Structures Flashcards
What is stereoisomerism?
Different configurations about one or more atoms (chiral centres)
Define enantiomers or optical isomers.
Non-superimposable mirror images (known as diastereomers)
Have identical chemical & physical properties but will rotate polarised light in opposite directions
Is glycine chiral or achiral?
Achiral
What is conformational isomerism?
Molecules that exist in different forms due to the rotation of bonds
Why is optical isomerism important in drug binding?
It affects the binding affinity to receptors
What are the two types of attachment in drug-receptor binding?
- Three-point attachment: High Affinity
- Two-point attachment: Low Affinity
How are enantiomeric pairs classified based on optical activity?
+/−
What does the D/L classification relate to?
Relationship to glyceraldehyde (AA and sugars)
What is the R/S Cahn Ingold Prelog system used for?
To classify enantiomers unambiguously as R (rectus) or S (sinister)
Who introduced the D/L classification system?
Emil Fischer in 1891
What does the lower case d/l denote?
The same as +/−
Give an example of an anomaly in stereochemistry.
L-nicotine
What is a chiral centre?
Usually a carbon with four different groups attached
How are substituents prioritized at the chiral centre?
Using the atomic NUMBER of atoms bonded to the chiral centre
How are double bonds treated in stereochemistry?
Like two single bonds
What is an example of a drug with stereoselective action?
Noradrenaline
What is the significance of the S form of Citalopram?
Only the S form is an antidepressant
Which compounds are associated with carvone?
- Caraway
- Spearmint
What is geometric isomerism?
cis-trans isomerism (E/Z)
Occurs where there is a double bond/ring structure that prevents the rotation of a bond
Importance of optical isomerism in drug binding
When a drug is optically active, one enantiomer will bind tighter to its protein target than the other
When trying to fit the ‘wrong’ optical isomer of a drug into the protein binding site, there’s not a good match between the bonding residues in the drug and the binding site = weak binding reaction
General principle of 3 point binding
If a protein selects between optical isomers of a drug, the drug must make at least 3 points of attachment to the protein
How are enantiomers classified by optical activity?
(+) enantiomer will rotate light clockwise
(-) enantiomer will rotate light anticlockwise
How are enantiomers classified based on D/L?
- First find chiral centre (carbon with 4 different groups attached)
- Prioritise the substituents (using the atomic number of atoms bonded to the chiral centre)
- Double bonds are treated like 2 single bonds
- If 2 atoms are the same, look at what is bonded to the substituent (e.g. if it is a H group, if Cl is bonded to the H it will take higher priority)
- Work along chain until you find the point of difference (where the groups differ)
How are drug structures represented?
Wedged line = group is facing forward
Dashed line = group is going backward
Normal line = in the plane of the screen
What is meant by implicit and explicit in drug representations?
Implicit refers to an unlabelled atom
Explicit refers to being represented as a letter e.g. C for carbon
Noradrenaline drug structure
R form is the natural form (OH group is facing forward)
45x more potent than the S form in binding beta2 receptors
Citalopram/escitalopram
Only the S form is an antidepressant —> binds to SERT 50x higher than the R form
Originally sold as a racemic mixture
Escitalopram = pure S form (has lower risk of side effects)
