Fundamentals of Medicinal Chemistry

Table 9.2

Examples of mixed function oxidase catalysed oxidations. Oxidation

introduces or reveals new functional groups (shaded). Note: these

reactions are not the only routes for the metabolism of the

drugs used as examples

Type of reaction (groups)

Example

Aromatic hydroxylation(aromatic C–H)

NHCOCH

N 2

NHCOCH

N 2

C

H 2

5

C

H 2

5

CH

3

CH

3

CH

3

CH

3

C

H 2

5

C

H 2

5

HO

Lignocaine

(local anaesthetic)

Aliphatic hydroxylation(aliphatic C–H)

CH

3

CH

−

CH

CH 2

−

CH

3

CO

CO NH

N

H

CH

3

CO

CH

−

CH

CH 2

CH 2

2

CO

CO NH

N

H

C

H 2

5

OH

C

H 2

5

CO

CYP

−

450

Pentobarbitone

(sedative, hypnotic)

Epoxidization(aromatic and alkene groups)

NCONH

2

NCONH

2

NCONH

2

O

HO

OH

Carbamazepine(anticonvulsant)

(continues overleaf

)

PHASE I METABOLIC REACTIONS 187