SAR2: lead to drugs Flashcards
What does para position mean?
Aromatic ring where the substituents are opposite each other.
What does meta position mean?
Aromatic ring where the substituents separated by one carbon atom.
What does ortho position mean?
Aromatic ring where the substituents next to each other.
How does a methoxy group affect the amine if its in para or ortho position?
Amine donates electrons in the para position
Nitro is withdrawing electrons from the para position.
Left - in para it would increase the ability to do h-bonding.
What does ADME mean?
Absorption, distribution, metabolism and elimination
What are the important factors for ADME?
Stability (chemical and metabolic).
Hydrophilic/hydrophobic balance (solubility).
Ionisation
Size
No. of H-bonds
What are the Lipinski’s rule of five?
An orally active drug has no more than one violation of the following criteria:
* No more than 5 hydrogen bond donors.
* No more than 10 hydrogen bond acceptors.
* A molecular mass less than 500 Daltons.
* LogP value does not exceed 5.
What can be to reduce polarity?
Form ester or amide from carboxylic acid.
Form amide from amine.
What can be done to increase polarity?
Add OH group.
Add amine
Add Heterocycle
What is LogP?
P = Partition coefficient
Equal to:
* Conc of drug in octanol/conc of drug in water.
* Octanol gives a good approximation of absorption in the gastrointestinal system.
What happens if logP is high?
Drugs won’t get into cells and reach active site.
What happens if drugs are too ionised (pKa above or below 6-8)?
Tend to be poorly absorbed.
What form is it best to give drugs in?
Orally
Are groups susceptible to acid cleavage good?
No - acid stable compounds - stomach acid
Which groups are susceptible to acid cleavage?
Esters, amides, penicillin’s (beta-lactams)
