Barbiturates

Barbiturates- SAR, Drugs

1. Barbiturates M.K. Munde Mcpl , Moshi

2. Barbiturates Use SAR MOA Drugs Barbituric acid  is  6-hydroxyuracil  is an organic compound and the parent structure of all barbiturates

3. USE Barbiturates are a group of drugs that have calming effects on the body. They can produce effects similar to those of alcohol, ranging from mild relaxation to an inability to feel pain and loss of consciousness. Sedative, hypnotic  Anticonvulsant Preoperative Sedation ( Anesthesia )

4. SAR General structure of Barbiturates SAR of Barbiturates consists of: 1. Substitution of R 1 and R 2 2. Substitution of X 3. Substitution of R 3 and R 4 . SAR

5. 1. Substitution of R 1 and R 2 Generally substituted with hydrogen or alkyl group. Alkyl group at first position may have a shorter onset and duration of action. Methyl group substitution results in a barbiturates which is weak acid and therefore readily enters CNS.

6. 2. Substitution of X X could be substituted with oxygen or sulphur . Generally it is substituted with oxygen . Substitution with sulphur makes barbiturates more lipid soluble and onset is fast with shorter duration of action .

7. 3.Substitution of R 3 and R 4 • Both R 3 and R 4 should not be substituted with hydrogen. •Increasing the length of alkyl chain at position 5 may enhance the potency of the drug. •Branched, cyclic, or unsaturated chain produce shorter duration of action.

8. 4. Substitution at 4th and 6th position Carbonyl group (C=O ) is essential for activity.

9. MOA Like benzodiazepines, barbiturates potentiate the effect of GABA at GABA A receptor. In addition to this GABAergic effect, barbiturates also block  AMPA  and  kainate receptors, subtypes of ionotropic glutamate receptor.

10. Barbiturates Name R 1 R 2 IUPAC Name Allobarbital CH 2 CHCH 2 CH 2 CHCH 2 5,5-diallylbarbiturate Amobarbital CH 2 CH 3 (CH 2 ) 2 CH(CH 3 ) 2 5-ethyl-5-isopentyl-barbiturate Aprobarbital CH 2 CHCH 2 CH(CH 3 ) 2 5-allyl-5-isopropyl-barbiturate Alphenal CH 2 CHCH 2 C 6 H 5 5-allyl-5-phenyl-barbiturate Barbital CH 2 CH 3 CH 2 CH 3 5,5-diethylbarbiturate Brallobarbital CH 2 CHCH 2 CH 2 CBrCH 2 5-allyl-5-(2-bromo-allyl)-barbiturate Pentobarbital CH 2 CH 3 CHCH 3 (CH 2 ) 2 CH 3 5-ethyl-5-(1-methylbutyl)-barbiturate Phenobarbital CH 2 CH 3 C 6 H 5 5-ethyl-5-phenylbarbiturate Secobarbital CH 2 CHCH 2 CHCH 3 (CH 2 ) 2 CH 3 5-[(2 R )-pentan-2-yl]-5-prop-2-enyl-barbiturate; 5-allyl-5-[(2R)-pentan-2-yl]-barbiturate H.W.

11. Name R 1 R 2 Allobarbital CH 2 CHCH 2 CH 2 CHCH 2 Allobarbital Example

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