Synthesis and Anti-inflammatory Activity of Some Novel 1,5 Benzodiazepine Derivatives

Objective: The objective of the study is to synthesize some novel 1,5-benzodiazepine derivatives from chalcones. The structures of the newly synthesized compounds were characterized by elemental analysis, infrared, 1H nuclear magnetic resonance, and mass spectroscopic studies. All titled compounds were screened for their anti-inflammatory activity. Methods: In this study, a series of novel 2-(substituted phenyl)-3-styryl-2,3-dihydro-1H-benzo [b] [1,4] diazepine (1-12) has been synthesized from 1,5-(disubstituted phenyl)-2,4-pentadien-1-one (1a-12a). 1,5-(disubstituted phenyl)-2,4-pentadien-1-one was prepared by condensing cinnamaldehyde with various aromatic ketones in the presence of 20% NaOH as base. Different 1,5-(disubstituted phenyl)-2,4-pentadien-1-one on cyclisation with o-phenylene diamine in the presence of NaOH as base resulted in 2-(substituted phenyl)-3-styryl-2,3-dihydro-1H-benzo [b] [1,4] diazepine derivatives. The final synthesized benzodiazepine derivatives were screened for their anti-inflammatory activity using carrageenaninduced rat paw edema method. Results: The compounds 4, 5, 7, 9, 10, 11, and 12 containing 4-nitrophenyl, 4-chlorophenyl, 3-nitro phenyl, 4-fluorophenyl, 4-bromophenyl, and 3-chlorophenyl benzodiazepine derivatives exhibited significant anti-inflammatory activity compared with the standard diclofenac sodium The presence of electron withdrawing groups such as nitro, chloro, fluoro, and bromo resulted in increased anti-inflammatory activity. Conclusion: This study reports the successful synthesis of 1,5-benzodiazepine derivatives with moderate yields and most of the synthesized compounds showed significant anti-inflammatory activity.