Drug Metabolism in Drug Design and Development Basic Concepts and Practice

OH

O

O

NH

NH 2

H

S

O

N

H

OH

O

H

R

O

HNH

S

O

R OH

O

HO S

O N

OH

O

HO S OH

O N

O

HO S

O N

OH

NC

CN

HO S

OH

O

N

H

OH

S

HN

O

OH

O

OH

O

O

NH

NH

H

S

O

N

H

OH

O

H

S

O

O

N

R

O

O

O

I O

NH 2

Compound A

Compound C

Glutathione (R = H) and its

S-conjugate (R = xenobiotic moiety)

N-Acetylsysteine (R = H) and its

S-conjugate (R = xenobiotic moiety)

Neutral loss

of 129 Da Neutral lossof 129 Da

Compound B

Compound D

R-(+)-Pulegone

Dansyl glutathione (R = H) and its

S-conjugate (R = xenobiotic moiety)

Menadione (2-methyl-1,4-naphthoquinone) Iodoacetamide (IAM)

FIGURE 14.1 The structures of glutathione and its conjugate,N-acetylcysteine and its
conjugate, (2S,3R)-3-(4-hydroxyphenyl)-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2,3-dihy-
dro-1,4-benzoxathiin-6-ol (A) and its bis–cyano adduct (B), (2S,3R)-(+)-3-(3-hydro-
xyphenyl)-2-[4-(2-pyrrolidin-1-ylethoxy)-phenyl]-2,3-dihydro-1,4-benzoxathiin-6-ol (C)
and itsN-acetylcysteine adduct (D), dansyl glutathione,R-(+)-pulegone, menadione,
and iodoacetamide.

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