Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation, cartilage damage and bone destruction. Although the pharmacological treatment of RA has evolved over the last few years, the new drugs have serious side effects and are very expensive. Thus, the research has been directed in recent years towards new possible targets. Among these targets, N-formyl peptide receptors (FPRs) are of particular interest. Recently, the mixed FPR1/FPR2 agonist Cpd43, the FPR2 agonist AT-01-KG, and the pyridine derivative AMC3 have been shown to be effective in RA animal models. As an extension of this research, we report here a new series of pyridinone derivatives containing the (substituted)phenyl acetamide chain, which was found to be essential for activity, but with different substitutions at position 5 of the scaffold. The biological results were also supported by molecular modeling studies and additional pharmacological tests on AMC3 have been performed in a rat model of RA, by repeating the treatments of the animals with 10 mg/kg/day of compound by 1 week.

Pyridinone Derivatives as Interesting Formyl Peptide Receptor (FPR) Agonists for the Treatment of Rheumatoid Arthritis / Crocetti, Letizia; Vergelli, Claudia; Guerrini, Gabriella; Giovannoni, Maria Paola; Kirpotina, Liliya N.; Khlebnikov, Andrei I.; Ghelardini, Carla; Di Cesare Mannelli, Lorenzo; Lucarini, Elena; Schepetkin, Igor A.; Quinn, Mark T.. - In: MOLECULES. - ISSN 1420-3049. - ELETTRONICO. - 26:(2021), pp. 6583-6583. [10.3390/molecules26216583]

Pyridinone Derivatives as Interesting Formyl Peptide Receptor (FPR) Agonists for the Treatment of Rheumatoid Arthritis

Crocetti, Letizia;Vergelli, Claudia;Guerrini, Gabriella;Giovannoni, Maria Paola;Ghelardini, Carla;Di Cesare Mannelli, Lorenzo;Lucarini, Elena;
2021

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation, cartilage damage and bone destruction. Although the pharmacological treatment of RA has evolved over the last few years, the new drugs have serious side effects and are very expensive. Thus, the research has been directed in recent years towards new possible targets. Among these targets, N-formyl peptide receptors (FPRs) are of particular interest. Recently, the mixed FPR1/FPR2 agonist Cpd43, the FPR2 agonist AT-01-KG, and the pyridine derivative AMC3 have been shown to be effective in RA animal models. As an extension of this research, we report here a new series of pyridinone derivatives containing the (substituted)phenyl acetamide chain, which was found to be essential for activity, but with different substitutions at position 5 of the scaffold. The biological results were also supported by molecular modeling studies and additional pharmacological tests on AMC3 have been performed in a rat model of RA, by repeating the treatments of the animals with 10 mg/kg/day of compound by 1 week.
2021
26
6583
6583
Goal 3: Good health and well-being for people
Crocetti, Letizia; Vergelli, Claudia; Guerrini, Gabriella; Giovannoni, Maria Paola; Kirpotina, Liliya N.; Khlebnikov, Andrei I.; Ghelardini, Carla; Di...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1247106
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