Quantative SARs Flashcards
How is biological activity quantified?
As log 1/C
What is P?
The partition co-efficient
What’s done in a QSAR study?
Single systematic changes at a single position, then measure drug properties
Also monitor hydrophobic, electronic and steric properties too
What occurs in studies where there is a small range of log P when plotted graphically?
A straight line graph is obtained
What is the relation as log P increases with respect to serum albumin binding?
Drugs bind to serum albumin protein more - log P increases
What is pi?
It is the substituent hydrophobicity constant, it is a measure of how hydrophobic a substituent is relative to hydrogen
How is the hydrophobicity constant found?
A standard compound is measured with, and without, the substituent
What equation gives the hydrophobicity constant?
LogPx - LogPH
Where PH is the partition coefficient for the standard compound, Px is with the substituent
What does a positive change of a substituents hydrophobicity constants mean?
It means the molecule is MORE hydrophobic, and so is more lipophilic
How do you find log P of a new compound?
Just add up the hydrophobicity constants of the components in the structure.
What’s the difference between logP and hydrophobicity constants?
Hydrophobicity constants are a measure of the hydrophobicity of a particular region on a candidate drug molecule
LogP is a measure of a drugs overall hydrophobicity
What is sigma?
The Hammett constant - it is a measure of the electron withdrawing / donating ability of a substituent
If an EWG is added to benzoic acid, what will happen to the position of equilibrium?
Position of equilibrium will move to the right, as the EWG can stabilise the -ve charge
If an EDG is added to benzoic acid, what will happen to the position of equilibrium?
The position of equilibrium will move to the left - forming a less powerful acid as the -ve charge is destabilised.
Will benzoic acids have a larger or smaller Hammett constant with EWGs?
EWGs will have a larger Hammett constant
A smaller Hammett constant is with EDGs
What is the typical form of a Hansch equation?
What is the equation for finding the Hammett constant of a given molecule?
Where KH indicates that the benzoic acid is unsubstituted
What is KH equal to wrt benzoic acids?
Product / reactant = KH
It is an equilibrium constant
What is the Hammett constant for hydrogen?
0 - by definition
Where is the functional group for Hammett substituent constants?
At the meta or para positions on aromatic ring of benzoic acids
What is given by the symbol Es?
The Taft Steric Parameter - it relates to the importance of size and shape of a drug molecule
What does the Craig plot show?
The Hammett substituent constant is on the y-axis
A substituents hydrophobicity constant is therefore on the x-axis
It shows there is no relationship between the two parameters.
What is a Topliss Scheme?
It is a flow diagram that allows med-chemists to decide what substituents to place in an aromatic ring of a lead compound.
What’s the first stage of a Topliss Scheme?
It involves preparing a 4-chloro analogue of the lead compound
