ABSTRACT
In the present study a series of O-substituted pyrazoles 7(a-f) and N-substituted pyrazoles 9(a-f) were synthesized via phase-transfer catalyzed reaction of ethyl 5-(bromomethyl)-1,3-diphenyl-1H-pyrazole-4-carboxylate 5 with various oxygen and nitrogen containing compounds in presence of tetrabutylammonium bromide (TBAB) in THF. The compound 5 was obtained by the efficient bromination with N-bromosuccinimide (NBS) in presence of a catalytic amount of azoiso-bis-butyro nitrile (AIBN) in refluxing CCl4. The synthesized compounds were evaluated for their in vitro antimicrobial and antidiabetic activity and were compared with standard drugs. Among the synthesized compounds, compound 9b emerged as an excellent antimicrobial and antidiabetic agent. Newly synthesized compounds were characterized by analytical and spectral (IR, (1)H NMR, (13)C NMR and LC-MS) methods.
Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Pyrazoles/chemistry , Anti-Infective Agents/chemical synthesis , Catalysis , Chemistry Techniques, Synthetic , Drug Evaluation, Preclinical/methods , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Hypoglycemic Agents/chemical synthesis , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Docking Simulation , Structure-Activity Relationship , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/chemistry , alpha-Amylases/metabolism , alpha-Glucosidases/metabolismABSTRACT
A novel series of 2-(5-methyl-1,3-diphenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazoles 7(a-m) were synthesized either by cyclization of N'-benzoyl-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 4a using POCl3 at 120°C or by oxidative cyclization of hydrazones derived from various arylaldehyde and (E)-N'-benzylidene-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 5(a-d) using chloramine-T as oxidant. Newly synthesized compounds were characterized by analytical and spectral (IR, (1)H NMR, (13)C NMR and LC-MS) methods. The synthesized compounds were evaluated for their antimicrobial activity and were compared with standard drugs. The compounds demonstrated potent to weak antimicrobial activity. Among the synthesized compounds, compound 7m emerged as an effective antimicrobial agent, while compounds 7d, 7f, 7i and 7l showed good to moderate activity. The minimum inhibitory concentration of the compounds was in the range of 20-50µgmL(-1) against bacteria and 25-55µgmL(-1) against fungi. The title compounds represent a novel class of potent antimicrobial agents.
