Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 11.1 (

Continued

)

Metabolic reaction

Description

Molecular formulachange

m

/z

change

R–CH

OCH 2

CH 2

! 3

R–COOH

Ethyl ether to acid

–C

H 2

+O 6



14.0519

R–CH

! 3

R–H

Demethylation

–CH

2



14.0157

R–C(CH

) 3

! 3

R–COOH

Tert

-butyl to acid

–C

H 3

+O 8

2



12.0726

R–CH

COCH 2

3

!

R–COOH

Methyl ketone to acid

–C

H 2

+O 4



12.0363

R–CH

CH 2

! 3

R–OH

Ethyl to alcohol

–C

H 2

+O 4



12.0363

R–CH

–CH 2

–CH 2

–CH 2

–R 2

0!

R–CH = CH–CH = CH–R

0

Two sequential

desaturation

–H

4



4.0314

Hydroxylation + dehydration

Hydroxylation +

dehydration

–H

2



2.0157

R–CH

–OH 2

!

R–CHO; R–CHOH–R

0!

R–CO–R

0

Primary/secondary

alcohols toaldehyde/ketone

–H

2



2.0157

R–CH

–CH 2

–R 2

0!

R–CH = CH–R

0

Desaturation

–H

2



2.0157

C

H 5

N 7

!

C

H 5

N 5

1,4-Dihydropyridines to

pyridines

–H

2



2.0157

R–F

!

R–OH

Oxidative defluorination

–F + OH



1.9957

R–CHNH

–R 2

0!

R–CO–R

0

Oxidative deamination to

ketone

–NH

+O 3



1.0316

R–CH

OCH 2

! 3

R–COOH

Demethylation and

oxidation to acid

–CH

4

+O



0.0365

R–CH(OH)CH

! 3

R–COOH

2-Ethoxyl to acid

–CH

4

+O



0.0365

R–CH

–NH 2

2

!

R–CH

–OH 2

Oxidative deamination

to alcohol

–NH + O

0.9840

R–CH(CH

) 3

! 2

R–COOH

Isopropyl to acid

–C

H 2

+O 6

2

1.9430

R–CH

! 3

R–OH

Demethylation and

hydroxylation

–CH

2

+ O

1.9792

332