Recent Structure Activity Relationship Studies of 1,4-Benzodiazepines

Abstract

Structure activity relationship studies of 1,4-benzodiazepines have been discussed especially with their effects as antianxiety and anticonvulsants. The currently available benzodiazepines are associated with various side effects. Nowadays the purpose of these studies is to minimize side effects with these drugs. A very little alteration is possible on the benzene ring while the modification can be done on the diazepine ring. It can adopt the different conformations and in some cases some aromatic and heterocyclic rings have been fused with this part in order to see the effect of these conformation blockers on the pharmacological activity. The structure activity studies are also linked to molecular modeling studies. This is important in adding some information for the interaction of these drugs with the receptors and how this interaction can be improved. Chemistry and biological activity The discovery of BDZs dates back to 1950 and the first agent which was introduced in the market was chlordiazepoxide. Diazepam, the second member of this series was more active [7]. Introduction of substituent is very important in BDZs especially the position 7. The potency of these compounds also increases by adding the substituent's in ring B and C [8]. Triazolo BDZs which contains triazole ring fused with diazepine nucleus are most potent agents in this class [9,10](Figure 1). Furan and thiophene are the bioisosteres of the phenyl ring [11]. 5-thienyl and 5-furyl substituted BDZs were synthesized and evaluated for their affinity at the BDZs receptors in order to get information about the binding of lipophilic pocket and its effect on the biological activity. The 5-(2'-thienyl) BDZs showed high affinity for the BDZs receptors which displaced flunitrazepam from rat cortical membrane with high affinity and were anticonvulsant and muscle relaxant. When a bromine atom was substituted at position 4', the compound was less active. The 5-(3'-thienyl) and 5-(2'-furyl) were less potent. The 2'-halo substituted phenyl was more potent than the 2'-thienyl and 2'-furfuryl [12] (Figure 2).