Synthesis and Chemoinformatic Analysis of Fluorinated Piperidines as 3D Fragments for Fragment-Based Drug Discovery.

Publication date: Mar 07, 2024

The concise synthesis of a small library of fluorinated piperidines from readily available dihydropyridinone derivatives has been described. The effect of the fluorination on different positions has then been evaluated by chemoinformatic tools. In particular, the compounds’ pK’s have been calculated, revealing that the fluorine atoms notably lowered their basicity, which is correlated to the affinity for hERG channels resulting in cardiac toxicity. The “lead-likeness” and three-dimensionality have also been evaluated to assess their ability as useful fragments for drug design. A random screening on a panel of representative proteolytic enzymes was then carried out and revealed that one scaffold is recognized by the catalytic pocket of 3CL (main protease of SARS-CoV-2 coronavirus).

Concepts Keywords
Chemoinformatic Based
Coronavirus Chemoinformatic
Dihydropyridinone Concise
Library Derivatives
Random Dihydropyridinone
Discovery
Drug
Evaluated
Fluorinated
Fragment
Fragments
Library
Piperidines
Small
Synthesis

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