Medicinal Chemistry (CHM2254/CHM60604)

Tutorial 3

1. Describe how the scintillation proximate assay makes use of a specific radioisotope which
interacts with a scintillant to emit light. (4 marks)
Scintillation proximate assay involves the immobilisation of a target molecule on beads coated
with a scintillant which emits light in the blue region of the visible spectrum. A ligand labelled
with 125I binds to the target and the radioisotope interacts with the scintillant to emit light.

2. Name and identify all the binding interactions that are possible for the functional groups
highlighted in the lead compound. Discuss the changes in terms of binding interaction of the
analogue compared to the lead compound (4 + 2 marks)

Dipole-dipole interaction (C), HBA (A), HBD (D and A), van der waals force (D).
Analogue compound has ionic bond (D), and loss of hydrogen bond donor (A).

3. Explain how you would apply the principles of rigidification to structure below in order to
improve its pharmacological properties. Give one specific example of rigidified structure for
the following structure. (5 marks)

The free single bonds present can freely rotate and the
entire structure is more flexible. Flexible structure can
cause side effects and reduced activity. The activity of the
structure can be improved by locking the free rotating bond
via ring introduction. Bonds in the ring are locked within
the structure where the bonds no longer rotate freely and
have improved activity. Example of structure by
introducing ring into the structure and locking the free
rotating bonds.