Synthesis, HPLC enantioresolution, and X-ray analysis of a new series of C5-methyl pyridazines as N-formyl peptide receptor (FPR) Agonists

Agostino Cilibrizzi, Letizia Crocetti, Maria Paola Giovannoni, Alessia Graziano, Claudia Vergelli, Gianluca Bartolucci, Giacomo Soldani, Mark T. Quinn, Igor A. Schepetkin, Cristina Faggi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The synthesis of three racemates and the corresponding non-chiral analogues of a C5-methyl pyridazine series is described here, as well as the isolation of pure enantiomers and their absolute configuration assignment. In order to obtain optically active compounds, direct chromatographic methods of separation by HPLC-UV were investigated using four chiral stationary phases (CSPs: Lux Amylose-2, Lux Cellulose-1, Lux Cellulose-2 and Lux Cellulose-3). The best resolution was achieved using amylose tris(5-chloro-2-methylphenylcarbamate) (Lux Amylose-2), and single enantiomers were isolated on a semipreparative scale with high enantiomeric excess, suitable for biological assays. The absolute configuration of optically active compounds was unequivocally established by X-ray crystallographic analysis and comparative chiral HPLC-UV profile. All compounds of the series were tested for formyl peptide receptor (FPR) agonist activity, and four were found to be active, with EC50 values in the micromolar range. Chirality 25:400-408, 2013.

Original languageEnglish
Pages (from-to)400-408
Number of pages9
JournalChirality
Volume25
Issue number7
DOIs
Publication statusPublished - Jul 2013
Externally publishedYes

Fingerprint

Pyridazines
Formyl Peptide Receptor
X ray analysis
Cellulose
Peptides
Amylose
Enantiomers
High Pressure Liquid Chromatography
X-Rays
Chirality
Biological Assay
Assays
X rays

Keywords

  • absolute configuration
  • chiral stationary phase
  • FPRs
  • inflammation
  • liquid chromatography
  • Lux Amylose
  • Lux Cellulose
  • pyridazinones

ASJC Scopus subject areas

  • Organic Chemistry
  • Analytical Chemistry
  • Drug Discovery
  • Pharmacology
  • Catalysis
  • Spectroscopy

Cite this

Cilibrizzi, A., Crocetti, L., Giovannoni, M. P., Graziano, A., Vergelli, C., Bartolucci, G., ... Faggi, C. (2013). Synthesis, HPLC enantioresolution, and X-ray analysis of a new series of C5-methyl pyridazines as N-formyl peptide receptor (FPR) Agonists. Chirality, 25(7), 400-408. https://doi.org/10.1002/chir.22162

Synthesis, HPLC enantioresolution, and X-ray analysis of a new series of C5-methyl pyridazines as N-formyl peptide receptor (FPR) Agonists. / Cilibrizzi, Agostino; Crocetti, Letizia; Giovannoni, Maria Paola; Graziano, Alessia; Vergelli, Claudia; Bartolucci, Gianluca; Soldani, Giacomo; Quinn, Mark T.; Schepetkin, Igor A.; Faggi, Cristina.

In: Chirality, Vol. 25, No. 7, 07.2013, p. 400-408.

Research output: Contribution to journalArticle

Cilibrizzi, A, Crocetti, L, Giovannoni, MP, Graziano, A, Vergelli, C, Bartolucci, G, Soldani, G, Quinn, MT, Schepetkin, IA & Faggi, C 2013, 'Synthesis, HPLC enantioresolution, and X-ray analysis of a new series of C5-methyl pyridazines as N-formyl peptide receptor (FPR) Agonists', Chirality, vol. 25, no. 7, pp. 400-408. https://doi.org/10.1002/chir.22162
Cilibrizzi, Agostino ; Crocetti, Letizia ; Giovannoni, Maria Paola ; Graziano, Alessia ; Vergelli, Claudia ; Bartolucci, Gianluca ; Soldani, Giacomo ; Quinn, Mark T. ; Schepetkin, Igor A. ; Faggi, Cristina. / Synthesis, HPLC enantioresolution, and X-ray analysis of a new series of C5-methyl pyridazines as N-formyl peptide receptor (FPR) Agonists. In: Chirality. 2013 ; Vol. 25, No. 7. pp. 400-408.
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