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

Результат исследований: Материалы для журналаСтатья

6 Цитирования (Scopus)

Аннотация

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.

Язык оригиналаАнглийский
Страницы (с-по)400-408
Число страниц9
ЖурналChirality
Том25
Номер выпуска7
DOI
СостояниеОпубликовано - июл 2013
Опубликовано для внешнего пользованияДа

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ASJC Scopus subject areas

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

Цитировать

Cilibrizzi, A., Crocetti, L., Giovannoni, M. P., Graziano, A., Vergelli, C., Bartolucci, G., Soldani, G., Quinn, M. T., Schepetkin, I. A., & 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