1) 9-aminoacridines are antimalarial drugs derived from acridine, which is formed by fusing an additional benzene ring to pyridine in quinoline. 2) Introducing certain functional groups or side chains at different positions on the acridine nucleus can enhance or reduce antimalarial activity. For example, adding a side chain at the 9 position makes it antimalarial. 3) Examples of antimalarial 9-aminoacridines include quinacrine, which was one of the first synthetic antimalarials, and chloroquine, which was developed from quinacrine.

1. 9-aminoacridines
Antimalarial drugs

2. Acridines
• Aacridine is formed when an additional benzene
ring is fused with pyridine ring of quinoline
nucleus. Acridine is overall aromatic, though
having nitrogen
Pyridine
Quinoline Benzene

3. 9-Amino acridine
• has an amino group at C -9
• It is a green fluorescent dye
• In the past, the compound was used as an
antiseptic for treating wounds infections

4. Structure Activity Relationship
• Various types of acridines were synthesized
• Acridine has weak antiseptic and antibacterial
activity
• When a side chain – 2 amino, 5 diethylamino
pentane- is introduced at C-9, the compound
becomes antimalarial
• When methoxy at position 2 and Cl at 6 are
introduced –quinacrine- which is antimalarial
• Quinacrine was the 1st synthetic agent that
was used before quinolines

5. 9
2
6
Quinacrine

6. • When methoxy is shifted to position 6 and Cl to
2 (interchanged)-loss of antimalarial activity
• When methoxy is replaced by ethoxy, toxicity is
increased
• When methoxy is rotated to any other position
1, 3, 4, then 50% activity is lost
• When Cl is replaced with other halogens there is
successive loss of activity

7. • Side chain – 2 amino, 5 diethylamino pentane-
has no antimalarial activity but when attached
to aromatic system the compound became
antimalarial
• When at position-1, a N is introduced –
azacrine- which has good antimalarial activity
and rapid onset of action

8. Azacrine

9. • A very useful drug was taken from quinacrine by
Gemans by separating it into two halves;
• 1 half chloroquine active
• 2 half was inactive

11. Chemical synthesis
(p-methoxy aniline)
2, 4 dichloro benzoic acid
Condensation reaction

12. -HCl
2, p-methoxy phenyl amino, 4 chloro benzoic acid

13. POCl3
6- chloro , 2-methoxy acredinone

14. POCl3
6, 9 dichloro, 2-methoxy acredine

15. 2
6 chloro, 9 diethylaminopentyl, 2-methoxy, acredine

16. Therapeutic uses
• Treating erythrocytic stage of malaria
• Earlier, was used in treating black water fever
• Have anthalmentic activity against intestinal
parasites
• It is eliminated slowly and have side effects

17. Non-therapeutic use
• Being green fluorescent dye, used to visualize
blood cells, particularly platelets
• Platelets store the dye in dense granules

18. Side effects
• Gastric irritation
• Staining of tongue and skin