Question $2$

$[$Answer All Parts$]$

Part $($a$)$

$[50$ Marks$]$

The following compound $1$ shows anticancer activity through Tankyrase

inhibition. Further work led to the development of a $1-$D QSAR equation for

structure $2$ shown below.

$log\frac{1}{C}=0\mathrm{.}398+1\mathrm{.}089+4\mathrm{.}541$

$($i$)$ Propose a workplan that can be used to identify the pharmacophore for $1$

and explain what relevant information will be obtained from each product

of your synthetic transformations $($detailed synthetic methods are not

required$).[20$ marks$]$

$($ii$)$ Predict the biological activity for $2$ where $R=$OMe,$Br,$ and $N{O}_2.$

marks$]$

$($iii$)$ Structure $3$ was identified as the new lead from $3-$D QSAR studies.

Unfortunately, compound $3$ suffered from poor water solubility. Propose a

prodrug for $3$ that will have enhanced water solubility, include a synthesis

for your proposed prodrug and explain how the lead will be released in

vivo. $[20$ marks$]$