2,4‐Disubstituted 5‐Nitroimidazoles Potent against Clostridium difficile

Autor: Séverine Péchiné, Patrice Vanelle, Tri Hanh Dung Doan, Claire Janoir, Carole Di Giorgio, Fanny Mathias, Jean Innocent, Maxime D. Crozet, Cédric Spitz, Sylvain Pellissier
Přispěvatelé: Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2019
Předmět:
Cell Survival
medicine.drug_class
[SDV]Life Sciences [q-bio]
Antibiotics
CHO Cells
01 natural sciences
Biochemistry
Structure-Activity Relationship
Cricetulus
Metronidazole
Drug Resistance
Bacterial
Drug Discovery
medicine
Nucleophilic substitution
Animals
Humans
[CHIM]Chemical Sciences
Sulfones
General Pharmacology
Toxicology and Pharmaceutics
ComputingMilieux_MISCELLANEOUS
Pharmacology
Molecular Structure
Clostridioides difficile
[CHIM.ORGA]Chemical Sciences/Organic chemistry
010405 organic chemistry
Vicarious nucleophilic substitution
Chemistry
Organic Chemistry
Clostridium difficile
Combinatorial chemistry
Clostridium difficile infections
Anti-Bacterial Agents
3. Good health
0104 chemical sciences
010404 medicinal & biomolecular chemistry
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Nitroimidazoles
Drug Design
Clostridium Infections
Molecular Medicine
Anaerobic bacteria
Antibacterial activity
medicine.drug
Zdroj: ChemMedChem
ChemMedChem, Wiley-VCH Verlag, 2019, 14 (5), pp.561-569. ⟨10.1002/cmdc.201800784⟩
ChemMedChem, 2019, 14 (5), pp.561-569. ⟨10.1002/cmdc.201800784⟩
ISSN: 1860-7187
1860-7179
DOI: 10.1002/cmdc.201800784
Popis: Metronidazole is one of the first-line treatments for non-severe Clostridium difficile infections (CDI). However, resistance limits its use in cases of severe and complicated CDI. Structure-activity relationships previously described for the 5-nitroimidazole series have shown that functionalization at the 2- and 4-positions can impart better activity against parasites and anaerobic bacteria than metronidazole. Herein we report the synthesis of new 2,4-disubstituted 5-nitroimidazole compounds that show potent antibacterial activity against C. difficile. We used a vicarious nucleophilic substitution of hydrogen (VNS) reaction to introduce a phenylmethylsulfone at the 4-position and a unimolecular radical nucleophilic substitution (SRN 1) reaction to introduce an ethylenic function at the 2-position of the 5-nitroimidazole scaffold.
Databáze: OpenAIRE
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