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 language | English |
|---|---|
| Pages (from-to) | 400-408 |
| Number of pages | 9 |
| Journal | Chirality |
| Volume | 25 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2013 |
| Externally published | Yes |
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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
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 journal › Article
}
TY - JOUR
T1 - Synthesis, HPLC enantioresolution, and X-ray analysis of a new series of C5-methyl pyridazines as N-formyl peptide receptor (FPR) Agonists
AU - Cilibrizzi, Agostino
AU - Crocetti, Letizia
AU - Giovannoni, Maria Paola
AU - Graziano, Alessia
AU - Vergelli, Claudia
AU - Bartolucci, Gianluca
AU - Soldani, Giacomo
AU - Quinn, Mark T.
AU - Schepetkin, Igor A.
AU - Faggi, Cristina
PY - 2013/7
Y1 - 2013/7
N2 - 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.
AB - 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.
KW - absolute configuration
KW - chiral stationary phase
KW - FPRs
KW - inflammation
KW - liquid chromatography
KW - Lux Amylose
KW - Lux Cellulose
KW - pyridazinones
UR - http://www.scopus.com/inward/record.url?scp=84879415176&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879415176&partnerID=8YFLogxK
U2 - 10.1002/chir.22162
DO - 10.1002/chir.22162
M3 - Article
C2 - 23744588
AN - SCOPUS:84879415176
VL - 25
SP - 400
EP - 408
JO - Chirality
JF - Chirality
SN - 0899-0042
IS - 7
ER -