Chirality in drug design

Question 1

Enantiomers definition

Answer 1

A pair of stereoisomers that are non-identical mirror images of each other

Question 2

Diastereoisomers definition

Answer 2

A pair of non-identical stereoisomers that are not mirror images of each other

Question 3

Meso compound

Answer 3

A non-optically active stereoisomer containing a plane of symmetry

Question 4

R/S chiral centres

Answer 4

Classifies a chiral centre by the groups around it, within a pair of enantionmers one will be R and the other S

Question 5

D/L chiral centres

Answer 5

Classifies a chrial centre by comparison to a reference compound (glyceraldehyde). Within a pair of enantiomers, one will be D, the other L

Question 6

d/l chiral centres

Answer 6

Classifies a molecule that may contain more than one chiral centre by the direction that it rotates polarised light
d- dextrorotatory (clockwise)
l- levorotatory (anti-clockwise)
Does not correlate with D/L, rarely used today

Question 7

+/- chiral centres

Answer 7

Same as d/l. d = +, l = -

Used in preference to avoid confusion with D/L

Question 8

Two approaches to obtaining pure chiral molecules:

Answer 8

Chrial separation- use a physical method, e.g. chromatography, to separate the desired stereoisomer from a mixture
The chiral pool- use a starting material that already contains a chiral centre

Question 9

Eutomers and distomers

Answer 9

For a pair of stereoisomers: the isomer with the greater activity is the eutomer, the isomer with lower activity is the distomer

Question 10

Chiral switch

Answer 10

The development of a single isomer drug from a previously marketed racemate

Question 11

Advantages of the chiral switch

Answer 11

Improved biological activity
Modified dosage
More selective (no off-target binding)
Reduced side effects
Simpler pharmacokinetics
An opportunity to market a new product