Tamiflu was designed to mimic sialic acid but the 4'-hydroxyl was changed to 4'-amine (primary). Why was this done? and what changes to the molecule (PD/PK) has it achieved?
PD/PK = Pharmacodynamics-pharmacokinetics
I have tried to answer these questions, but I'm still unsure about what changes in (PD/PK) has it achieved when there replaced OH with an amine. Hope you can explain it to me.
My own answer so far:
Tamiflu was designed to have a similar structure to sialic acid, which is a substrate for viral neuraminidase enzyme. It acts as a competitive inhibitor. The replacement of hydroxyl group to an amine group is to improve binding interaction. As the result from diverse studies showed that the binding region that normally occupied by 4-OH of sialic acid could also interact with an aminium ion.
The replacement of these two groups will improve pharmacokinetic.....???
In term of pharmacodynamic, there will form a stronger hydrogen bonding in the amine group compared to the hydroxy group, which lead to a more potent inhibitor......???