SAR of Benzodiazepine 

This presentation contains SAR of Benzodiazepine:
The presence of electron-attracting substituents (-Cl, -F, -Br, -NO2) at position 7 is required for activity, and the more electron attracting leads to more activity
Positions 6, 8, and 9 should not be substituted
The presence of a phenyl or pyridyl (bromazepam) at the 5-position increases activity, and all benzodiazepines has this substituent
5-Phenyl ring with electron-attracting (generally halogen atoms) groups at the 2′, or 2’, 6’- position show greatly increased activity
e.g. Lorazepam, Triazolam, Midazolam
On the other hand, substitution in 3’, 4’ and 5’ decreases or abolishes activity
Almost all active benzodiazepines have a carbonyl group at position 2, except those possessing a fused heterocyclic ring or a thionyl group
Addition of methyl group to the nitrogen at position 1, yields a prototype benzodiazepine diazepam.
This drug exhibits all three of the basic benzodiazepine effects skeletal muscle relaxation, anticonvulsant activity and anti-anxiety effects
The N-substituient at position 1 should be small for higher intrinsic activity
Saturation of 4, 5 double bond or shift of double bond to the 3,4 position decreases the activity
Alkyl substituents at 3-position decrease the activity, whereas substitution of the 3-position with polar hydroxyl and carboxyl group retain activity and have short half lives. e.g. Oxazepam
Derivatives with additional rings (triazole or imidazole) joining the diazepine nucleus at the 1 and 2 positions are generally active.
e.g., Triazolam, Alprazolam
Reduction of carbonyl function at 2-position to -CH2 gives less potent
Replacement of the benzene ring by heteroaromatic (thiophene) ring
#AmitLunkad
resulted in enhanced anxiolytic properties
compounds