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Barbiturates
M.K. Munde
Mcpl, Moshi
Barbiturates
• Use
• SAR
• MOA
• Drugs
Barbituric acid is 6-hydroxyuracil is an organic compound and
the parent structure of all barbiturates
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)
SAR
General structure of Barbiturates
SAR of Barbiturates consists of:
1. Substitution of R1 and R2
2. Substitution of X
3. Substitution of R3 and R4.
SAR
1. Substitution of R1 and R2
• 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.
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.
3.Substitution of R3 and R4
•Both R3 and R4 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.
4. Substitution at 4th and 6th position
• Carbonyl group (C=O) is essential for activity.
MOA
• Like benzodiazepines, barbiturates potentiate
the effect of GABA at GABAA receptor.
• In addition to this GABAergic effect,
barbiturates also block AMPA and kainate
receptors, subtypes of ionotropic glutamate
receptor.
Barbiturates
Name R1 R2 IUPAC Name
Allobarbital CH2CHCH2 CH2CHCH2 5,5-diallylbarbiturate
Amobarbital CH2CH3 (CH2)2CH(CH3)2
5-ethyl-5-isopentyl-
barbiturate
Aprobarbital CH2CHCH2 CH(CH3)2
5-allyl-5-isopropyl-
barbiturate
Alphenal CH2CHCH2 C6H5 5-allyl-5-phenyl-barbiturate
Barbital CH2CH3 CH2CH3 5,5-diethylbarbiturate
Brallobarbital CH2CHCH2 CH2CBrCH2
5-allyl-5-(2-bromo-allyl)-
barbiturate
Pentobarbital CH2CH3 CHCH3(CH2)2CH3
5-ethyl-5-(1-methylbutyl)-
barbiturate
Phenobarbital CH2CH3 C6H5 5-ethyl-5-phenylbarbiturate
Secobarbital CH2CHCH2 CHCH3(CH2)2CH3
5-[(2R)-pentan-2-yl]-5-prop-
2-enyl-barbiturate; 5-allyl-5-
[(2R)-pentan-2-yl]-
barbiturate
H.W.
Name R1 R2
Allobarbital CH2CHCH2 CH2CHCH2
Allobarbital
Example
Thank You

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Barbiturates

  • 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 R1 and R2 2. Substitution of X 3. Substitution of R3 and R4. SAR
  • 5. 1. Substitution of R1 and R2 • 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 R3 and R4 •Both R3 and R4 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 GABAA receptor. • In addition to this GABAergic effect, barbiturates also block AMPA and kainate receptors, subtypes of ionotropic glutamate receptor.
  • 10. Barbiturates Name R1 R2 IUPAC Name Allobarbital CH2CHCH2 CH2CHCH2 5,5-diallylbarbiturate Amobarbital CH2CH3 (CH2)2CH(CH3)2 5-ethyl-5-isopentyl- barbiturate Aprobarbital CH2CHCH2 CH(CH3)2 5-allyl-5-isopropyl- barbiturate Alphenal CH2CHCH2 C6H5 5-allyl-5-phenyl-barbiturate Barbital CH2CH3 CH2CH3 5,5-diethylbarbiturate Brallobarbital CH2CHCH2 CH2CBrCH2 5-allyl-5-(2-bromo-allyl)- barbiturate Pentobarbital CH2CH3 CHCH3(CH2)2CH3 5-ethyl-5-(1-methylbutyl)- barbiturate Phenobarbital CH2CH3 C6H5 5-ethyl-5-phenylbarbiturate Secobarbital CH2CHCH2 CHCH3(CH2)2CH3 5-[(2R)-pentan-2-yl]-5-prop- 2-enyl-barbiturate; 5-allyl-5- [(2R)-pentan-2-yl]- barbiturate H.W.
  • 11. Name R1 R2 Allobarbital CH2CHCH2 CH2CHCH2 Allobarbital Example