Highly Efficient Base-Catalyzed Synthesisof Piperidine-4-Imine Lead Molecules For SARS-Cov-2 Mutant Spike Proteasevia In Silico Method

Abstract

For the discovery of drugs to SARS-CoV-2 pandemics, we have developed a new series of piperidine-4-imines as the central core owing to significant pharmaceuticaldemands on it. The synthesis of piperidine-4-imines involvesatwo-step base-catalyzed reaction, namely (i)condensations followed by cyclization with aromatic aldehyde, aliphatic ketone, and ammonia to yield piperidine-4-ketone core, and (ii) a simple Schiff base/piperidine-4-imines formation between piperidine-4-ketone andvarious aromatic primary amines. All the synthesized intermediate and target piperidine-4-imines molecular structures were well characterized by NMR, FT-IR, and mass spectral studies.

Further, the ground state geometry of synthesized molecules was optimized using density function theory (DFT) with basis set of b3lyp 6-31g (d,p) in Gaussian 09 program. Using this molecular geometry, we docked against SARS-CoV-2 mutant spike protease of delta, delta plus, and omicron, which shows an effective binding ability. In addition, Lipinski’s rule, pre ADME and toxicity studies also reveal drug-likeness properties.