SAR OF BARBITURIC ACID
BARBITURIC ACID
Highly ionized (water soluble), fully
aromatic, tautotmeric structure (B).
At least one of the nitrogen atoms
should have Hydrogen to allow the
partial enolization.
MODIFICATIONS AT N-ATOMS
Alkylation of one N gives compounds
characterized by faster onset of action
but shorter duration
Dialkylation results in inactive
compounds due to the positive charge
will apear
Larger alkyl substituents may lead to
convulsant activity.
MODIFICATION OF OXYGEN
Replacement of Oxygen between
two Nitrogen by Sulfur Result in
faster onset and ultra-short
duration
MODIFICATIONS AT C-5
total number of C-atoms in both of R1
and R2 should be within 4-8.
Branching or unsaturation results in
greater activity but shorter duration.
Alicyclic and aromatic substituents
give higher potency.
(OH, NH2, COOH) abolish the activity.
—> water soulable (ionaized)