L1-2 Drug binding, SAR and analogue design

Key reading chapters

Recall enzyme inhibitors

https://knowt.com/flashcards/ad02f753-f81b-469d-b7e6-7bbdda3e9483

card 13 on uncompetitive

Recall receptors

https://knowt.com/flashcards/a0c20b3c-6bfa-4bb5-b95a-e610d1818acc

card 12 

Inverse agonist

a ligand that decreases the ‘resting’ activity of a receptor (i.e. where the receptor activity in absence of an agonist)

What is an SAR

Strructure-activity relationships - relationship between 3D chemical structure of a molecule and its biological activity.

How is SAR determined

By making analogues during the hit-to-lead phase.

Small changes to a molecules strucutre and the effect that has on acitivity can be used. Too many chnages at once makes it much harder to interpret results.

What is an isostere

Molecules that have the same number of electrons on its outer shell.

Notes on determining SAR

What is the scaffold and what is scaffold hopping

The central core around which functional groups are typically arranged - typically stuff like aromatic rings which are flat and rigid.

Changing this central scaffold is called scaffold hopping.

What is the pharmacophore

The pharmacophore is the 3D collection of steric and electronic features neededto ensure optimal interactions with a specific target and to trigger (or block) its biological response.