Fundamentals of Medicinal Chemistry

Table 9.2

(continued)

Type of reaction (groups)

Example

Dealkylation(methyl and ethyl secondary amines, tertiary amines,tertiary amines, ethers and thioethers. The methanaland ethanal produced are often excreted via the lungs,giving the patient bad breath.)

N

N

N

(CH

) 2

3

NH CH

3

(CH

) 2

3

NH

2

HCHO

HCHO

(CH

) 2

N(CH 3

) 3

2

Desmethylimipramine

(antipsychotic)

Imipramine

(antidepressant)

NHCOCH

3

CH

CH 3

O 2

CH

CHO 3

HO

NHCOCH

3

Paracetamol (analgesic)

Phenacetin (analgesic)

SCH

3 N

N

N

+ HCHO

N

NH

N

N

NH

SH

6 −

Mercaptopurine (anticancer)

6 −

Methylthiopurine

Oxidative dehalogenationThe reactive electrophilic acyl and carbonylcompounds produced by oxidative dehalogenationmay react with nucleophilic biological molecules suchas DNA, proteins, lipids and carbohydrates topossibly form toxic metabolites.

Highly reactive xamyl chloride derivative

O

N 2

CH

−

CH

O

N 2

CH

−CH

OH

CH

OH 2

NH

−

C

−

C

−

Cl

OH

CH

OH 2

Cl

NH

−C

−

O

H

Cl

O

O

C

+ HCl

Chloramphenicol (antibiotic)

188 DRUG METABOLISM