Physicochemical Properties 1

Question 1

what drug properties do physicochemical properties relate to?

Answer 1

1. activity
2. pharmacokinetics
3. formulation
4. toxicology
5. overall drug-likeness

Question 2

what must an ideal oral drug be able to do?

Answer 2

1. bind
2. dissolve
3. survive pH range
4. survive intestinal bacteria
5. cross membranes
6. survive liver metabolism.
7. avoid active transport to bile
8. avoid excretion by kidneys
9. partition into target organ
10. avoid partition into undesired places.

Question 3

what must be known about the drug molecule before it can be given to a patient?

Answer 3

1. solubility
2. logP
3. stability
4. metabolism
5. pKA
6. solid state properties

Question 4

define a physicochemical property?

Answer 4

• a parameter derived from physical and chemical properties of a molecule
• turning the molecular structure into numbers that correlate to the drug’s properties

Question 5

what factors are included in the physicochemical property of a molecule?

Answer 5

• solubility
• stability
• solid-state properties
• partition coefficient
• ionisation constant

Question 6

What is SAR and QSAR?

Answer 6

SAR: structure-activity relationship
QSAR: quantitative structure-activity relationship (using maths to link chemical structure to pharmacological activity)

Question 7

What is Lipinski’s rule of 5 for an orally available compound?

Answer 7

1. no more than 5 Hbond donors in the molecule
2. no more than 10 hydrogen bond acceptors
3. molecular mass less than 500
4. logP less than 5

Question 8

What does Lipinski’s rule tell us?

Answer 8

it’s a guideline to determine how drug-like a compound is

Question 9

What is lipophilicity?

Answer 9

the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents

Question 10

What is use to determine how lipophilic a compound is?

Answer 10

the partition coefficient (P)

Question 11

how do you calculate partition coefficient?

Answer 11

(conc of drug in octanol) divided by (conc of drug in water)

Question 12

what two methods can be used to determine logP?

Answer 12

1. shake flask method

2. chromatography

Question 13

What is the relationship between drug binding and logP?

Answer 13

as logP increases, binding increases

Question 14

what is a ‘substituent hydrophobicity constant’?

Answer 14

a measure of a substituents hydrophobicity relative to hydrogen

Question 15

what does a positive ‘substituent hydrophobicity constant’ imply?

Answer 15

that the substituents are more hydrophobic than H.

Question 16

what does a negative ‘substituent hydrophobicity constant’ imply?

Answer 16

that the substituents are less hydrophobic than H.

Question 17

how do you calculate logP using ‘substituent hydrophobicity constant’?

Answer 17

clogP = logP (of main chain e.g. benzene) + total substituent hydrophobicity constant for all substituents attached.

Question 18

what is the ‘distribution coefficient (D)’?

Answer 18

• the ratio of the sums of all forms (ionised and unionised) of the compound in each of the two phases.
• it is quoted at the pH of the aqueous phase

Question 19

what equation is used to calculate logD?

Answer 19

logD = (conc of drug in octanol) divided by (sum of ionised and unionised drug concentrations in water)

Question 20

When do you use logP and logD?

Answer 20

logP and logD can both be used depending on compound type or drug target

Question 21

when do you use logP and not logD?

Answer 21

1. when comparing neutral molecules

2. when comparing a mixture of neutral and charged molecules

Question 22

when do you used logD and not logP?

Answer 22

when comparing all charged molecules