phase 1 reactions of metabolism of drugs

This slide includes complete description of phase I reactions that occur during the metabolism phase of drugs that we can intake.

1. DrugMetabolismWays
1-PhaseI Reactions(oxidation, reduction, hydrolysis,
hydrationetc.)
2-PhaseII Reactions-Conjugationreactions

2. 1-PhaseI Reactions
Its purpose is to make the molecule more polar.

3. Theintroductionofapolarfunctionalgroupistointroduceanew
functionalgrouptothemolecule,suchasinhydroxylation
reactions,ortoreplaceanexistingfunctionalgroup(forexample,
hydrolysisofesterstocarboxylicacidsandalcohols,oxidationof
alcoholstoacids,reductionofaldehydesandketonesto
alcohols).
Inthisway,themoleculebecomesmorepolarandmoreeasily
disposable.

4. 1. OXIDATION REACTIONS
•Aromaticoxidation(Aromatichydroxylation)
•Alken epoxidation
•Oxidationof aliphaticandalicycliccarbonatoms
•Oxidationof carbonsadjacenttoan sp2 center
(Oxidationof carbonatomsin benzyl, allylicandcarbonylorimine α-position)
•Oxidationof carbon-nitrogensystems
(OxidativeN-dealkylation, oxidativedeamination, N-oxideformation, N-hydroxylation)
•Oxidationof carbon-oxygensystems(OxidativeO-dealkylation)
•Oxidationof carbon-sulfursystems
(OxidativeS-dealkylation, S-oxidation, desulfurization)
•Alcoholandaldehydeoxidation

5. 2. REDUCTION REACTIONS
Reduction of carbonyl (aldehyde, ketone)
Nitro reduction
Azo reduction
3. HYDROLYSIS REACTIONS
Hydrolysis of esters and amides

6. AromaticHydroxylationOH
OH
H
H
O
OH
OH
Naftalen
Aren oksit (kanserojen)
%95
%5
+

7. AliphaticHydroxylation
ve -1 hydroxylation

8. Epoxidationox
O
Benzopiren
Benzopiren-4,5-epoksit

9. N-dealkylationN
NCl
O
CH
3
N
NCl
O
OH
N
NCl
O
H
+
CH
2
O
Diazepam

10. O-dealkylation

11. S-Dealkilasyon

12. OxidativeDeaminationNH
2
CH
3
Amfetamin
NH
2
CH
3
OH
Dayanıksız ara ürün
CH
3
O
+NH
3
Fenil aseton

13. N-OxidationN
CH
3
ox

14. S-Oxidation

15. Dehalogenation

16. 2-ReductionReactions
AzocompoundsNH
2
NH
2
NN
S
O
O
NH
2
Prontosil
NH
2
NH
2
NH
2
+
NH
2
S
O
O
NH
2
Sülfanilamid
NitrocompoundsNHCOCHCl
2
N
+
O
-
O
OH
OH
NHCOCHCl
2
OH
OH
NH
2
Kloramfenikol

17. Heterocyclicring compounds
DoublebondsR
O
N
N
NH
2
Halka yarılması
R
NH
2
OH
N
NH R R' R R'
DisulphuresR
S
R'
S
R
SH
R'
SH+

18. Hydrolysisreactions
Ester hydrolysisEt
Et
NH
2
O
O N
Prokain
Et
Et
N
OH
NH
2
O
OH
+
plazma
esteraz
AmidehydrolysisEt
CH
3
CH
3
NH
O
NH
Monoetil glisil ksilid
amidaz
Et
NH
O
OH
CH
3
CH
3
NH
2
+
Ksilidin
Etil glisin