Drug Metabolism in Drug Design and Development Basic Concepts and Practice

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TABLE 11.1 Common biotransformations and the corresponding elemental composition and


m


/z


changes.


Metabolic reaction

Description

Molecular formulachange

m
/z

change

R–CH

C 2

H 6

! 5

R–H

Debenzylation

–C

H 7

6



90.0468

R

79
Br

!

R

H

Reductive debromination

–Br + H



77.9104

R–CF

! 3

R–H

Trifluoromethyl loss

–CF

+H 3



67.9874

2R



35
Cl

!

2R


H

2

reductive dechlorination

–Cl

+H 2

2



67.9222

R

79

Br

!

R

OH

Oxidative debromination

–Br + OH



61.9156

R–C(CH

) 3

! 3

R–H

Tert

–butyl dealkylation

–C

H 4

8



56.0624

R–ONO

! 2

R–OH

Hydrolysis of nitrate ester

–NO

+H 2



44.9851

R–COOH

!

R–H

Decarboxylation

–CO

2



43.9898

R–CH(CH

) 3

! 2

R–H

Isopropyl dealkylation

–C

H 3

6



42.0468

R–CH

COCH 2

CH 2

CH 2

3
!

R–COOH

Propyl ketone to acid

–C

H 4

+O 8



40.0675

R–C(CH

) 3

! 3

R–OH

Tert

-butyl to alcohol

–C

H 4

+O 8



40.0675

2R–F

!

2R–H

2

reductive defluorination

–F

+H 2

2



35.9811

R

35

Cl

!

R

H

Reductive dechlorination

–Cl + H



33.9611

R–CH

OH 2

!

R–H

Hydroxymethylene loss

–CH

O 2



30.0106

R–NO

! 2

R–NH

2

Nitro reduction

–O

+H 2

2



29.9742

R–CH

OCH 2

CH 2

CH 2

! 3

R–COOH

Propyl ether to acid

–C

H 3

+O 8



28.0675

R–C

H 2

! 5

R–H

Deethylation

–C

H 2

4



28.0312

R–CO–R

0!

R–R

0

Decarboxylation

–CO



27.9949

R–CH

COCH 2

CH 2

! 3

R–COOH

Ethyl ketone to acid

–C

H 3

+O 6



26.0519

R–CH(CH

) 3

! 2

R–OH

Isopropyl to alcohol

–C

H 3

+O 6



26.0519

R–CH

–CH 2

OH 2

!

R–CH = CH

2

Alcohols dehydration

–H

O 2



18.0105

R–CH = N–OH

!

R–CN

Dehydration of oximes

–H

O 2



18.0105

R–F

!

R–H

Reductive defluorination

–F + H



17.9906

R

35

Cl

!

R

OH

Oxidative dechlorination

–Cl + OH



17.9662

RR

0 S=O

!

R–S–R

0

Sulfoxide to thioether

–O



15.9949

R–NHNHR

0 C=S

!

R–NHNHR

0 C = O

Thioureas to ureas

–S + O



15.9772
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