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.

• Such drugs have OCH3 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

• 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

• OCH3 is not necessary for antimalarial activity but when replaced by OC2H5 the compound became – less active– Toxic in nature

• OCH3 when replaced by CH3 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

• 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

Chemical synthesis (pamaquine)

• Glycerol undergoes dehydration to produce propene aldehyde

• Dehydrating agent is sulphuric acid

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

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

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

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

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

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