8 aminoquinolines

1. 8-aminoquinolines
•Drugs in this group have amino group at
position 8 of quinoline ring
•Important members of this
family include
1- Pamaquine
2- Primaquine, etc.

2. •Such drugs have OCH
3
group at position 6
•This molecule has antimalarial
activity but when side chain
is introduced at amino
group antimalarial activity is
intensified e.g
pamaquine
•It causes hemolysis
of RBCs
Diethyl amino pentyl side chain

3. •It contains tertiary amino group and when it is
converted into primary amino group the
compound is called primaquine, which is
–Less toxic
–Well tolerated
–It is the most commonly used agent in this group
in the treatment of malaria

4. •OCH
3
is not necessary for antimalarial activity
but when replaced by OC
2
H
5
the compound
became
–less active
–Toxic in nature
•OCH
3
when replaced by CH
3
the compound
become inactive
•Introduction of halogens increases toxicity
•Presence of quinoline ring is necessary for
antimalarial activity. When pyridine ring is
converted to piperidine (saturated) the
compound became inactive

5. •Pentyl side chain gives maximum activity,
increase or decrease of chain result is reduction
of activity.
•The branched side chain when converted into
straight chain pentaquine is obtained
•It has less antimalarial activity as compared to
both pamaquine and primaquine

6. Chemical synthesis (pamaquine)
•Glycerol undergoes dehydration to produce
propene aldehyde
•Dehydrating agent is sulphuric acid

7. •Addition reaction of propene aldehyde and 4
methoxy 2-nitro aniline to form 4 methoxy 2-
nitro propene aldehyde

8. •Tautomerization: 4 methoxy 2-nitro propene
aldehyde (keto form) converted in enol form

9. •Enol form undergoes cyclization to form 8 nitro 6
methoxy dihydroquinoline which then oxidized to
form 8 nitro 6 methoxy quinoline

10. •6 methoxy 8 nitro quinoline undergoes
reduction to form 8 amino 6 methoxy
quinoline

11. •8 amino 6 methoxy quinoline reacts with 2
chloro diethyl amino pentane to form
pamaquine

12. Therapeutic uses
•Active against hepatic stage of plasmodium
•Provide radical cure hepatic stage of P. vivax
and P. ovale
•It also acts at gametocytes, hence used as
prophylactic drugs
•Used in combination with chloroquine for
complete eradication of malaria
•Side effect: hemolysis in G6 phosphate
dehydrogenase deficient people