L23 - Metabolism And Drug Synthesis Flashcards
What is salbutamol?
B2 agonist
- used to treat COPD - Chronic obstructive pulmonary disease
What are the steps in the synthesis of salbutamol?
- formation of an ester
- friedel crafts acylation
- enol as nucleophile
- immine via condensation reaction
- reduction
How does the formation of an ester occur for the formation of salbutamol?
Salicylic acid + EtOH, Acid = Ester
How does Friedel Crafts acylation occur for the formation of salbutamol?
Methyl salicylate + acyl chloride
= desired product - methyl salicylate + ketone at the para,meta position
How does enol as a nucleophile occur for the formation of salbutamol?
Desired product + Br2 (via enol) = Br extensino to ketone
How does immine via condensation reaction occur for the formation of salbutamol?
+ NH2 (Sn2)
- lp on N attacks C on C-Br
How does reduction occur for the formation of salbutamol?
LiAlH4, Et2O
- ketone becomes secondary alcohol
What is the active enantiomer of salbutamol?
R
What is pharmacokinetics and the 4 areas?
The study of what the body does to a drug
- absorption
- distribution
- metabolism
- excretion
What is drug metabolism?
The chemical process to conert drugs into compounds that are easier to eliminate
What do metabolic enzymes make drugs in general?
More polar
- Drug (lipophilic) -> metabolite (hydrophilic)
Where does most drug metabolism occur?
In the liver
What is phase 1?
- oxidation
- reduction
- hydrolysis
What is phase 2?
Make drug (conjugates/metabolite) conjugates
Attach ionised group to increase polarity/aid excretion
What are examples of ionised groups that increase polarity/aid excretion?
- methyl
- acetyl
- glucoronidation
- amino acids
- glutathione
