CA1 Organic Medicinal Chemistry - Topic 13 CNS Depressants: Benzodiazepines & Barbiturates

Vocabulary flashcards covering key concepts, SAR details, and representative drugs from benzodiazepines and barbiturates as discussed in the CNS depressants lecture notes.

Benzodiazepines

A class of anxiolytic CNS depressants that increase the frequency of GABA-A receptor–mediated chloride channel openings, producing a calming effect.

GABA

Gamma-aminobutyric acid, the primary inhibitory neurotransmitter in the CNS.

GABA-A receptor

Ionotropic receptor; when activated by GABA, increases chloride ion conductance to inhibit neuronal firing.

Electron-withdrawing group (EWG)

A chemical group that pulls electron density; in benzodiazepine SAR, examples include NO2, Br, CF3, Cl and can increase activity at certain positions.

Ring A (in benzodiazepines)

The benzene ring whose electronic substituents influence activity; substituents on Ring A can modulate potency.

Ring B (in benzodiazepines)

Second ring essential for activity; contains features (e.g., carbonyl interactions) important for receptor binding.

Ring C (5-phenyl)

The fifth ring (5-phenyl) in the BZD scaffold; not required for binding but can enhance favorable steric/hydrophobic interactions.

7-position substitution on Ring A

Substitution at position 7 with electron-withdrawing or other groups increases BZD activity and binding.

Substitutions on Ring A at 6, 8, and 9

Substitutions at these positions tend to decrease benzodiazepine activity.

2-position carbonyl oxygen on Ring B

Proton-accepting group at Ring B position 2 necessary for interaction with the receptor (historically noted as interacting with histidine).

3-position substituents on Ring B

Hydroxyl at position 3 increases excretion; alkyl groups at position 3 decrease activity.

Ring C 5-phenyl contribution

The 5-phenyl group on Ring C is not required for binding but can provide favorable steric/hydrophobic interactions.

Fused BZD derivatives (triazolo/imidazole)

Benzodiazepines fused with an additional electron-rich ring (triazole or imidazole) yielding high receptor affinity and activity.

Triazolobenzodiazepines

Benzodiazepines fused with a triazole ring; typically short-acting (e.g.,Triazolam, Alprazolam).

Triazolam

A short-acting benzodiazepine from the triazolobenzodiazepine class.

Alprazolam

A short-acting benzodiazepine, example of a triazolobenzodiazepine.

Imidazobenzodiazepine

Benzodiazepines fused with an imidazole ring; typically short-acting (e.g., Midazolam).

Midazolam

A short-acting imidazobenzodiazepine used clinically for sedation and anesthesia.

Barbiturates

CNS depressants; MOA: increase the duration of GABA-A–mediated chloride channel opening; potent CNS inhibitory effects.

Barbituric acid core

The core nucleus: 2,4,6-trioxohexahydropyrimidine (barbituric acid).

Thiobarbiturates

Barbiturates where sulfur substitutes at the 2-position; more lipid-soluble, rapid CNS penetration, and shorter duration of action.

Thiopental

A highly lipid-soluble thiobarbiturate with rapid onset and short duration; used as an induction agent in anesthesia.

Sulfhydryl (thiol) group effect in barbiturates

Incorporating –SH groups tends to enhance lipophilicity and speed of CNS effects, leading to rapid onset (and often shorter duration) of action.