Optimising binding interactions

Question 1

Why is it important to optimize binding interactions with a target?

Answer 1

to increase activity and reduce dose levels, and to increase selectivity and reduce side effects

Question 2

Ways of optimising binding interactions

Answer 2

varying alkyl substituents, varying acyl substituents, extension, chain extension, ring expansion, isosteres, simplification and rigidification

Question 3

Explain the reason why we vary alkyl substituents

Answer 3

two reasons: firstly alkyl group in the lead compound may interact with hydrophobic region in binding site so varying length and bulk of group will optimize interaction / secondly it will introduce selectivity

Question 4

Explain the reason why we vary aryl substituents

Answer 4

varying substitution pattern can increase interactions eg. moving a group to a different location

Question 5

Explain the reason behind the extension (adding extra functional groups)

Answer 5

to explore target binding site for further binding regions to achieve additional interactions

Question 6

Explain the reason why we extend or contract the chain

Answer 6

it’s useful when there is a chain present connecting two binding groups. Varying chain length will optimize interactions