Medicinal Chemistry e-content for Pharmacy students

1. SAR OF SULPHONAMIDES
PRESENTED BY:
Mr. Purushotham K N
Asst. Professor
Dept. of Pharm.Chemistry
SACCP, B.G Nagar
1

2. SAR OF SULPHONAMIDES
N1 Substituted sulphonamides
• The free amino group (-NH2) is essential for activity. However it can
be replaced by groups which can be reconverted it back to free amino
group eg, succinyl amido, acetamido and phthalyl amido group.
NH R4
S
O
O
NH
R1

3. • The sulphanilamide skeleton is the minimal structural requirement for
antibacterial activity.
• Sulphur should be directly linked to the benzene ring.
S
NH2
O
O
NH2
NH R4
S
O
O
NH
R1

4. • The amino and sulfonyl radical should be 1, 4 position; 1, 2 and 1, 3
isomers are therapeutically less active.
• Any substitution on aromatic ring or replacement of benzene ring by
other ring decreases or abolishes the activity.
NH R4
S
O
O
NH
R1
NH R4
S
O
O
NH
R1

5. • Substitution of hetero cyclic aromatic nucleus in N1 position yields
highly potent compound.
• N' disubstitution in general, leads to inactive compound because one
hydrogen is essential for ionization.
• Maximum antibacterial activity is exhibited by sulphonamides having
pKa values between 6.6 to 7.4.
NH R4
S
O
O
NH
R1

6. • The lipid solubility influences the pharmacokinetic and antibacterial
activity. In general as the lipid solubility increases, the half life and
antibacterial activity (invitro) also increases.