Drug design Flashcards
What are the IDEAL characteristics of a drug for oral delivery?
Drug design
Limpinskis rule:
- LogP <_ 5
- Less than 11 H-bond accepting groups
- Less than 6 H-bond donating groups
- Molecular weight less than or equal to 500 [weight <_500]
For absorption in the GIT
What is a Pro-drug?
Drug design
A drug that is inactive in-vitro (outside of the body) but active in-vivo.
what is IC_50
Drug design
The CONCENTRATION of a drug needed to inhibit a biological process by HALF.
What is the difference between pharmacodynamics and pharmacokinetics ?
Pharmacodynamics focuses on the effects of the drug on the body and its target whereas Pharmacokinetics focuses on what the body does to the drug as it is processed (LADME)
Antagonist to agonist comparison
They feature the same functional groups but antagonists tend to be larger
Agonist MOA
- Bind to receptor.
- The binding causes an ‘induced-fit’ reaction.
- Conformational change to the receptor occurs.
- Causes the activation of a secondary messenger.
Agonist remains unchanged
Antagonist MOA
- Binds to the receptor.
- Does NOT cause a conformation change.
What is a pharmacophore?
A molecular feature that is necessary for a specific action.
What happens to a tertiary amine in physiological pH?
It is protonated into a quartenary amine (with a possitive charge)
What happens to a carboxylic acid in physiological pH?
It is deprotonated into a O=O-R (with a negative charge)
Hydrogen bond donor
Also known as a proton donor, is an electronegative atom {N, O, F} that is covalently bonded to a hydrogen.
Hydrogen bond acceptor
When an electronegative species has an available lone pair of electrons.
What is important to remember when altering the structure of a drug?
To make only one change at a time in order to allow observation of possible changes.
If there are multiple changes then we don’t know which change caused the effect.
What functional groups are CONSIDERED BASIC ?
- Guanidine [pKa13.6]
- Tertiary amine [~pKa10]
- Imidazole[pKa 6.8]
- Pyridine [pKa 5.2]
- Aniline [pKa 4.6]
Generally speaking, only pKa 7 and above are considered basic
Is pyridine’s lone pair readily given away?
Yes, because the while the Nitrogen atom is part of the aromatic structure, the lone pair is not included in the aromaticity and therefore is not included in the conjugation.
This means that it is readily given away.