Fundamentals of Medicinal Chemistry

(4) See Table 9.3. The amide bond and the carboxylic acid group make the conjugate

more water soluble than the original aromatic acid.

(5) (a)

CH 3

N CH 3

COOC 2 H 5

Hydroxylation of the benzene ring.

Hydrolysis of the ester to

Cleavage of the N-CH 3 bond to

N

+

COOH

C 2 H 5 OH

HCHO

Ph COOC 2 H 5

+

N

H

(b)

N=NNNH 2 =N

NH 2 H 2 N NH 2

NHCOCH 3

Hydroxylation of the benzene ring.

Acylation

Reductive cleavage

(6) (a) To inactive the drug. Metabolism to inert metabolites that are sufficiently water

soluble to be readily excreted via the kidney.

(b) Thea-carbon of an ethyl group t-amine is hydroxylated and cleaved to form

methanal and the N-methylaminobenzene. Methanal could be excreted via the

lungs or be metabolized further to ethanoic acid. The N-methylaminobenzene

could be metabolically oxidized to the corresponding N-hydroxy compound or

dealkylated to aminobenzene and methanal.

(7) (a) A is metabolized faster than the drug, so it does not accumulate in the body.

(b) B to C is the main metabolic route, since this is a very much faster process than

BtoF.

(c) C to D; C will accumulate in the body. If C is pharmacologically active this

could pose potential clinical problems for a patient.

(8) To avoid fatal over-doses.

(9) See Section 9.8.3. Use a N-methyldihydropyridine derivative as carrier. This carrier

would require a substituent group that can bond to the dopamine diethanoate. The

best group for this purpose is probably a carboxylic acid group, since amides are

slowly hydrolysed. This means the prodrug has a good chance of reaching the

blood–brain barrier in sufficient quantity to be effective. Once the prodrug has

ANSWERS TO QUESTIONS 269