Medicinal chemistry tutorial 2 | Mishalni Kanakarajah

Medicinal Chemistry (CHM2254/CHM60604)

Tutorial 2

1. List all the rules for Lipinskis Rule of Five. (4 marks)

- Molecular weight < 500
- 5 hydrogen bond donor
- 10 hydrogen bond acceptor
- Log P < +5 (hydrophobicity)

2. a) Define half-life of a drug. (2 marks)

Half-life (t ) is the time taken for the amount of administered drug concentration
in the blood to reduce to half of its initial amount.

b) What is the usage of the half-life of a drug? (2

marks) It is used to calculate the frequency of the drug to be administered to ensure
steady- state concentration and avoid accumulation of toxicity due to overdose.

c) Morphine has a half-life of 3 hours. How much of the drug remains after 15 hours?
(2 marks)
The amount of drug remains after 15 hours are 1/16 of the initial amount of
morphine given. This is because for every 3 hours the amount of drug is halved
from its previous concentration (t3= 1, t6= , t9 = , t12 = 1/8, t15 = 1/16).

3. Morphine binds strongly to opioids receptors in the brain to produce analgesia. In vitro
studies on opioid receptors show that the quaternary salt of morphine also binds strongly.
However, the compound is inactive in vivo when injected intravenously. Explain this
apparent contradiction. (5 marks)
 The compound is inactive in vivo because it unable to cross the blood brain barrier for
it to bind opioid receptors. As the blood brain barrier is hydrophobic, the quaternary
salt of morphine which has positive charge unable to cross the membrane. The in vitro
test shows strong binding of the salt to the receptor as the drug does not pass through
the membrane of the isolated cells being used.