Quantative SARs

Question 1

How is biological activity quantified?

Answer 1

As log 1/C

Question 2

What is P?

Answer 2

The partition co-efficient

Question 3

What’s done in a QSAR study?

Answer 3

Single systematic changes at a single position, then measure drug properties

Also monitor hydrophobic, electronic and steric properties too

Question 4

What occurs in studies where there is a small range of log P when plotted graphically?

Answer 4

A straight line graph is obtained

Question 5

What is the relation as log P increases with respect to serum albumin binding?

Answer 5

Drugs bind to serum albumin protein more - log P increases

Question 6

What is pi?

Answer 6

It is the substituent hydrophobicity constant, it is a measure of how hydrophobic a substituent is relative to hydrogen

Question 7

How is the hydrophobicity constant found?

Answer 7

A standard compound is measured with, and without, the substituent

Question 8

What equation gives the hydrophobicity constant?

Answer 8

LogPx - LogPH

Where PH is the partition coefficient for the standard compound, Px is with the substituent

Question 9

What does a positive change of a substituents hydrophobicity constants mean?

Answer 9

It means the molecule is MORE hydrophobic, and so is more lipophilic

Question 10

How do you find log P of a new compound?

Answer 10

Just add up the hydrophobicity constants of the components in the structure.

Question 11

What’s the difference between logP and hydrophobicity constants?

Answer 11

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

Question 12

What is sigma?

Answer 12

The Hammett constant - it is a measure of the electron withdrawing / donating ability of a substituent

Question 13

If an EWG is added to benzoic acid, what will happen to the position of equilibrium?

Answer 13

Position of equilibrium will move to the right, as the EWG can stabilise the -ve charge

Question 14

If an EDG is added to benzoic acid, what will happen to the position of equilibrium?

Answer 14

The position of equilibrium will move to the left - forming a less powerful acid as the -ve charge is destabilised.

Question 15

Will benzoic acids have a larger or smaller Hammett constant with EWGs?

Answer 15

EWGs will have a larger Hammett constant

A smaller Hammett constant is with EDGs

Question 16

What is the typical form of a Hansch equation?

Answer 16

Question 17

What is the equation for finding the Hammett constant of a given molecule?

Answer 17

Where KH indicates that the benzoic acid is unsubstituted

Question 18

What is KH equal to wrt benzoic acids?

Answer 18

Product / reactant = KH

It is an equilibrium constant

Question 19

What is the Hammett constant for hydrogen?

Answer 19

0 - by definition

Question 20

Where is the functional group for Hammett substituent constants?

Answer 20

At the meta or para positions on aromatic ring of benzoic acids

Question 21

What is given by the symbol Es?

Answer 21

The Taft Steric Parameter - it relates to the importance of size and shape of a drug molecule

Question 22

What does the Craig plot show?

Answer 22

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.

Question 23

What is a Topliss Scheme?

Answer 23

It is a flow diagram that allows med-chemists to decide what substituents to place in an aromatic ring of a lead compound.

Question 24

What’s the first stage of a Topliss Scheme?

Answer 24

It involves preparing a 4-chloro analogue of the lead compound