russu: organic functional grps

alcohol

• hydroxyl groups

• -OH, O is sp3

• hydrophillic

• can be oxidize by air/metabolism —> C=O —> COOH

• CH3CH2OH → CH3CHOH → CH3COOH

why is ethanol a common co-solvent

• CH3CH2-OH

• hydrophobic & hydrophilic

• dissolve both polar and non-polar compounds

amine

• nitrogen bases

• Basic N containing groups

• can act as nuc

• except: quat amine is cationic, notbasic

weakly basic amines

• lone pair of N makes amines basic bc cant accept H+

• when amines att to an unsaturated system, its e- can participate in resonance —> less basic

amides vs aniline

amide: neutral, bc lp participates in resonance and can’t get H+

aniline: weakly basic

Aniline is a weak base because its nitrogen lone pair is only partially delocalized by a benzene ring, whereas amides are neutral because a strongly electron-withdrawing carbonyl group completely ties up the lone pair.

amidine

very strongly basic

• more than amides & amines

• C=N (N is sp2)

• lp of sp2 N can accpet H+, protonation has positive charge that is delocalized between two nitrogens

nitro vs nitroso

• nitroso is more reactive

  • fewer electronegative oxygen atoms, making its nitrogen atom more electron-deficient

carboxylic acid

COOH

• can act as Hbond donor or acceptor

carboxylic acid and sulfonamide (weak acid)

• Carboxylic acids can be metabolized relatively easily → replacing them with a sulfonamide can sometimes make the drug more metabolically stable (last longer)

• Bioisostere = a different chemical group that can replace another group while producing a similar biological effect.

  
  

carboxylic ester (ester is very reactive)

—COOCH3

• ester hydrolysis

  • reagents: h2o w/ acid or base or esterase

  • product: carboxylic acid + HOCH3

use of ester as prodrug

• ester bond is common bond for prodrugs

  • don’t survive in body very well

• prodrug: inactive/less active

  • once goes on body, intestinal esterase & lipases breaks the ester bond —> rel active ingredient

ex: Chloramphenicol palmitate

Chloramphenicol palmitate (prodrug)

• no bitter taste, used for infants, due to ester bond

• once goes in body, ester bond gets hydrolyzed by enzyme

Chloramphenicol (active antibiotic)

• bitter taste

esters used to taste mask

Taste Masking: Converting bitter or unpalatable APIs to ester prodrugs

• helps mask unpleasant tastes f drugs

what do func groups containing hydroxyl or ionizable groups do

• contribute to aqueous solubility of drug moc

what’s a common metabolism/ degradation pathway

• oxidation

are esters easily hydrolyzed

yes