ACIDS 2

acid chlorides and anhydrides as drugs

too unstable

good for synthesis - acylation of alcohols and amines

esters and amides as drugs

stable in storage and manufacture - so make good drugs

some are useful in prodrug design

why are amide not stable to aq acid and base relative to other acid groups

because of the mesomeric donation into carbonyl

amide bonds

N-C bond in an amide is short, strong and cannot freely rotate because it has some double bond character

penicillin MOA

inhibit bacterial enzyme transpeptidase

b-lactam ring is involved in the mechanism of inhibition

penicillin becomes covalently linked to the enzymes active site leading to irreversible inhibition

role of transpeptidase bacterial enzyme

involved in the synthesis of the bacterial cell wall

conclusions of penicillin MOA

- amide and carboxylic acid are involved in binding

- carboxylic acid binds as the carboxylate ion

- MOA involves b-lactam ring: activity related to b-lactam ring strain

- bicylic system increases b-lactam ring strain

sulfonamide chemistry

acidic - can ionize in aqueous basic solution improving solubility

relatively stable towards aqueous hydrolysis

act on folate cycle

sulfonamides MOA

inhibit folate synthesis pathway

- act as PABA analogues - sulfonamide can bind in the same manner following ionisation in blood

DRAW DIAGRAM

- the effect of this is to reduce the amount of catalytically active folate

Sulfaniliamide mimicks the structure of PABA. As a result of this it competes with PABA for the binding site of dihydropteroate synthase. Sulfaniliamide binds to the enzyme and prevents it from interacting with PABA. This inhibits the production of dihydropteroate and subsequently folic acid.

limitation of the sulfa drugs

allergic reactions

formation of crystalluria

they give toxic metabolites after the oxidation of the aromatic amine