1. Chloroquine is an important anti-malarial drug that is synthesized in two steps from 4-amino-1-diethylamino pentane. 2. It is used to treat and prevent malaria as well as amebiasis, but can cause allergic reactions or severe skin issues. 3. Pamaquine is another anti-malarial drug synthesized from 6-methoxy-quinolin-8-ylamine and (4-chloro-pentyl)-diethyl-amine. It was formerly used to treat malaria but can cause gastrointestinal, blood, or hemolysis issues in some patients.

1. Important Synthesis in
Medicinal Chemistry
Anti-Malarial Drugs

2. Chloroquine-Anti-Malarial Drug
Step-1
O
Ethylene oxide
+
N
H
H2
C
H3C
H2
C
CH3
Diethylamine
C H 3 O H
2 -D ie th y l am in o eth a n o l
C H 2 O H
H 2 C N
C 2 H 5
C 2 H 5
SOCl2
CH2Cl
H2C N
C2H5
C2H5
CH3COCH2COOC2H5
-HCl
CH3COCHCOOC2H5
C
H2
H2
C N C2H5
C2H5
KOH,Hydrolysis
-C2H5OH
-CO2
CH3CO(CH2)3N
C2H5
C2H5
LiAlH4
[H]
CH3CH
OH
(CH2)3N
C2H5
C2H5
-H2O
NH3
CH3C-(CH2)3N
C2H5
C2H5
NH2
Step-2
CH3C-(CH2)3N
C2H5
C2H5
NH2
N
Cl
Cl
4,7-Dichloro-quinoline
+ -HCl
Condensation
N
Cl
HNC
H
(CH2)3N
CH3
C2H5
C2H5
(7-Chloro-quinolin-4-yl)-(1,1-diethyl-2-methyl-pyrrolidin-2-yl)-amine
Or Chloroquine
4-Amino-1-diethylamino
pentane

3. Uses
-Chloroquine is used to treat or prevent malaria
-Chloroquine is also used to treat amebiasis
(infection caused by amoebae).
Adverse Effects
-signs of an allergic reaction (hives, difficult breathing,
swelling in your face or throat)
-severe skin reaction (fever, sore throat, burning eyes,
skin pain, red or purple skin rash with blistering and
peeling).

4. N
N H 2
H 3 C O
6 - M e t h o x y - q u i n o l i n - 8 - y l a m i n e
N
C2H5
C2H5
H2
C
C
H2
H2
C
CH
CH3
Cl
(4-Chloro-pentyl)-diethyl-amine
+ N
H N
H 3 C O
N
C H 3
C 2 H 5
C 2 H 5
Pamaquine
Synthesis of Pamaquine
Use
Pamaquine is an 8-aminoquinoline drug formerly used for the treatment of malaria.
Adverse Effects
Gastrointestinal reactions, methemoglobinemia, and in persons with G6PD deficiency, mild
to severe intravascular hemolysis.

5. Mechanism of action of Pamaquine
ROS=Reactive
oxygen species