Drug structure activity relationship

Question 1

What is Acetylcholine Pharmacophore

Answer 1

Acetyloxy (COOH3)
Ethylene
4 degree ammonium

Question 2

Describe changing the number of methylene groups

Answer 2

Hydrophobic contributor
Increasing chain length or ring size
- increases hydrophobicity
- Increase ease of crossing mem.
May allow stronger bonding to receptor

Question 3

Describe changing ring size & shape

Answer 3

Physical properties and drug binding
- 6,6,6-ring less optimal bonding to two hydrophobic pockets than 6,7,6-ring system
- May change interannular angles

Question 4

Describe changing degrees of unsaturation with double bonds

Answer 4

Removal of DBs -> increased flexibility
Introduction of DBs -> decreased flexibility and different activities/potencies
often increases rate of metabolism (site of metabolic reactivity)
Often increases degree of cytotoxicity and unwanted effects

Question 5

Describe the function groups

Answer 5

Methyl groups - if on aromatic ring may interfere with metabolism
Hydroxyl groups (H-bonding, solubility)
Amine group )H-bonding, ionisation)
Ester group & prodrugs

Question 6

What are hard drugs

Answer 6

Resistant to metabolism

Question 7

What are soft drugs

Answer 7

Predictable & controlled metabolism

Question 8

Describe Sulfonylureas

Answer 8

Potassium channel blockers to treat diabetes

Question 9

Describe Chlorpropamide

Answer 9

Longer half-life than tolbutamide

Question 10

What are Isosteres

Answer 10

Atoms or groups of atoms with same valency and similar physical properties - changing them gives information regarding pharmacophore
- OH->SH to increase in size
- O->CH2 to change polarity and bonding

Question 11

What are chiral isomers

Answer 11

Differ in arrangement of their atoms in space and cannot be superimposed

Question 12

Describe cytotoxicity as a parameter

Answer 12

Study a pool of derivatives with known physiochemical properties and measure dependent parameter