Things to remember when applying to drugs

Phase I

*Cytochrome P450 looks for sites most electron rich and least sterically hindered.

So aromatic rings with electron withdrawing groups (Halogens, Nitro, carboxylic acid etc..) are not oxidized.
*The same drug can be oxidized at different sites.

so when looking at a drug we look for

1-Aromatic (benzene ring) → para hydroxylation.

(R is the rest of the molecule)

2-Olifin (double bond) → diol 3- Methyl group attached to benzene (benzylic carbon) → alcohol
4-Methyl group attached to C=C (allylic carbon) → alcohol.

5-Carbon next to carbonyl and imin (benzodiazepine) → secondary alcohol
6-long chain → oxidation of ω (terminal) carbon or ω -1 (carbon before the terminal)
...........................→ alcohol

7-Alicyclic (saturated ring) → alcohol on para position .

8-Tertiary or secondary aliphatic amine → removal of a methyl group to give amine
.......(make sure to remove the smaller group)
.......(called oxidative dealkylation)
.......(make sure the alkyl group removed has H on it )
.......(if the other group is small will be removed in a second step)

9-Tertiary nitrogen (nitrogen with no hydrogen on it) → N-oxide.

10-Primary amine (R-CH2-NH2) → NH3 (amonia) + R-CHO (carbonyl)
.........(oxidative deamination)
.........(make sure the carbon next to N has H on it)

or

........R- NH2 → R-NO2 (nitro).

11-An OCH3 group R-OCH3 → R-OH (alcohol)+ HCHO

12-An (R-S-CH3) → removal of CH3 → R-SH + HCHO
..........the carbon removed should have H

or

..............→ Oxidation of the sulfur → Sulfoxide or sulfone.

13-A Sulfur attached to a carbon with double bond C=S → C=O (oxidative desufuration).

14- R-CH2OH (alcohol) → R-CHO (aldehyde) → R-COOH (acid).

15- R-COOCH2R' (ester) → RCOOH (acid)+ R'-CH2OH (alcohol).

16-R-HNCO-R' (amide) → R-NH2 (amine) + R-'COOH (acid)

all the functional groups produced above (aromatic OH ; NH2 ; C=O ; COOH ; SO2 ; NO2 ; SH etc...) will be conjugated in phase II.
*If a drug has a functional group before metbolism e.g. OH or COOH or aromatic NH2 etc.. It can go directly to phase II and conjugates this functional group to a conjugating agent (mostly glucoronic acid)
*Aromatic amines are famous for conjugation to Acetyl group.

Please apply all these rules to the drugs given in the lectures.

Good Luck