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