Medicinal Chemistry Presentation

Group # 05

● Bilal Bin Shoukat

● Kaleem Talib
● Zia ur Rehman

Sir Junaid Dar

 Medicinal Chemistry Presentation

SAR,Therapeutic applications & differences in:

● 4-aminoquinolones
● 8-aminoquinolones
● 9-aminoacridines
● Biguanides

4-aminoquinolones 8-aminoquinolones 9-aminoacridines Biguanides

4-Aminoquinoline
At C-3 & C-4 position, asymmetry is
not essential for Antimalarial activity.
Affects the pH Easily diffuses into
parasitic vacuoles &
Less/weakly schizontocidal
basic nature activity

Electron withdrawing group at 7th position have been

shown to decrease pKa of:
● Quinoline ring N-atom
● Tertiary amino Nitrogen in the alkyl side chain
➔ Halogen at 7th
position increases
activity.

➔ Halogen at any other

position causes
inactivity

● Substitution at 8th position-CH3

results in complete loss of Activity
4-Aminoquinolines Derivatives

Cl
 SAR of 8-Aminoquinolines

Compounds in this
group have amino
group on 8th position
of quinoline ring.

They have O-CH3 group

at position 6th.
C-3 modification;
Introduction of phenyl group SAR of Primaquine
produces less active
compounds

Introduction of small alkyl &

vinyl group at C-4 increases
activity e.g, 4-methyl
Primaquine.

C-5 modification;
5-phenoxy substitution may
increase tissue schizontocidal
activity

Methoxy group at Position 6 is

responsible for optimum activity if
replaced by methyl group ,the
compound will become inactive

The optimal activity appears to be

achieved in alkyl groups containing 5 Introduction of Halogens will
carbon atoms. Any increase or decrease induce toxicity
will cause reduction in activity
Medicinal chemistry
4-aminoquinolones,8-aminoquinolones,9amino acridines and Biquinides

Presented by:
Kaleem Talib
Zia ur Rehman
Aminoquinoline

● chloroquine has proved to be a highly effective, safe, and well-tolerated drug for the treatment and
prophylaxis of malaria.
● However, the emergence of chloroquine-resistant strains of the malarial parasite has underlined the
requirement for a synthetic alternative to chloroquine

Examples include amodiaquine, chloroquine, and hydroxychloroquine

Therapeutic Applications

• A variety of derivatives of 4-aminoquinoline are antimalarial agents useful in treating erythrocytic plasmodial
infections.
• used for.Ameobiasis - Hepatic
•Acute manifestations of Lepra reaction.
•Arthritis Rheumatoid
•Infectious mononucleosis
•Autoimmune disorder- Discoid lupus erythematous
8-Aminoquinoline is the 8-amino derivative of quinoline.
● It is structurally analogous to 8-hydroxyquinoline.
● The two nitrogen atoms are ideally situated to form complexes with metal ions. Derivatives of 8-
aminoquinoline are effective directing groups in organic synthesis

The derivatives primaquine, tafenoquine and pamaquine have been tested for anti-malaria activity.
Primaquine is still used routinely worldwide as part of the treatment of Plasmodium vivax and
Plasmodium ovale malaria

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 choloroquine for complete eradication of malaria
.9 aminoacridine
● 9-Aminoacridine (9-AA) is a polycyclic heteroaromatic compound with three fused rings that can be used
as specific fluorescent
● Its derivatives, which also have fluorescence properties and are typically colored, have a wide range of
applications such as biological activity against neurodegenerative diseases and protozoal parasites.

Therapeutic uses•

• Treating erythrocytic stage of malaria

• Earlier, was used in treating black water fever

• Have anthalmentic activity against intestinal parasites

4.Biguanide

• Phenformin and metformin introduced in 1950s

• Phenformin had high risk of lactic acidosis and withdrawn

•Metformin is only drug in class In clinical use

 9-Amino acridine

● It 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
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
● Decrease hepatic gluconeogenesis andincrease glycogenolysis.

● Enhance insulin sensitivity in liver andskeletal muscle.

● Have antihypertriglyceridemic activity.

● Block breakdow of fatty acids throughactivation of AMP-dependent protein kinases.

SAR

• Developed from galegine (isoamylene

guanidine) first isolated from Galega officinalis.

The biguanides are formed by linking two guanidine groups together with different side chains.

Physicochemical and Pharmacokinetic Properties

• Quickly absorbed from the small intestines.

• Bioavailability is 50% to 60%; peak plasma levels in 2 hours.

• Not protein bound and widely distributed.

• Not metabolized and excreted unchanged in the urine (t1/2 = 2 to 5 hours).

ADVERSE EFFECTS

Metformin: GI discomfort and diarrhea; l actic acidosis; metallic taste; impaired B12

absorption.
Clinical Applications

• Metformin (Glucophage, Glucophage XR) is

the first-line drug for the treatment of type 2 diabetes along with life style modifications.

• Can also be used to treat insulin

resistance in women with polycystic ovary syndrome.

• Do not use in patients with renal dysfunction

(serum creatinine >1.4- 5).

Metformin

• Little or no hypoglycaemic effect in non diabetics

• Hypoglycaemia in diabetics is very rare

• Does not stimulate pancreatic beta cells Improve lipid profile in diabetics

Uses

• First choice drug in all T2 DM except not tolerated/ contraindicated

•Prevent micro and macro vascular DM complications –

•Can be combined with other hypoglycaemic drug Improve ovulation and fertility in Polycystic
Ovary Syndrome

• metformin may help people with diabetes to lose weight by lowering their appetites.