Synthesis and Chemoinformatic Analysis of Fluorinated Piperidines as 3D Fragments for Fragment-Based Drug Discovery.
J Org Chem
; 89(7): 4932-4946, 2024 04 05.
Article
em En
| MEDLINE
| ID: mdl-38451837
ABSTRACT
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' pKa'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 3CLPro (main protease of SARS-CoV-2 coronavirus).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Descoberta de Drogas
/
Quimioinformática
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França