Question

15. Answer ALL parts of this question.

(a) In the hit-to-lead and lead optimisation phases of drug discovery, name 5

considerations that need to be monitored for potential small molecules of

interest.

(5 marks)

(b) The structure of the antibiotic Chloramphenicol is shown in (Figure Q15b).

What type of metabolism is responsible for glucuronide derivatisation of

this molecule and why would this transformation be favoured at the

primary hydroxyl (over the secondary) hydroxyl group?

(2 marks)

(c) Microtubule stabilisers may be used as anticancer agents. Propose a set

of four molecules from the literature that can be overlaid to give a common

pharmacophore. Label the key structural features that indicate some

similarity between the molecules.

(8 marks)