Organobase catalyzed synthesis of pyranopyrazoles with X-ray crystallography, docking and ADME studies

Abstract

An organobase assisted approach is adopted to synthesize pyranopyrazole derivatives in one pot. Three-component condensation reaction of 3-methylpyrazolin-5-ones, aromatic aldehydes and malononitrile were catalyzed by 5 mol% of 4-dimethylaminopyridine (DMAP) in ethanol at room temperature. Key aspects of this approach are simple filtration without the need of time-consuming column purification; good yields; cost-effectiveness and use of easily available solid organo-base as a catalyst. A broad substrate scope and variety of functional group tolerance permit diversity generation in a one pot operation. In silico, molecular-docking studies of the compounds were performed with anti-inflammatory active drugs i.e. indomethacin and celecoxib and the compounds were also studied for their pharmacokinetic properties absorption, distribution, metabolism, and excretion (ADME). The results obtained for most of the synthesized compounds are promising and all of them comply well satisfying the Lipinski rule of 5 (RO5) with 0 violation.

Keywords

• Heterocycles
• Pyranopyrazoles
• DMAP
• Docking studies
• ADME